A Japanese Encephalitis Virus Vaccine Inducing Antibodies Strongly Enhancing In Vitro Infection Is Protective in Pigs

PubMed Central

García-Nicolás, Obdulio; Ricklin, Meret E.; Liniger, Matthias; Vielle, Nathalie J.; Python, Sylvie; Souque, Philippe; Charneau, Pierre; Summerfield, Artur

2017-01-01

The Japanese encephalitis virus (JEV) is responsible for zoonotic severe viral encephalitis transmitted by Culex mosquitoes. Although birds are reservoirs, pigs play a role as amplifying hosts, and are affected in particular through reproductive failure. Here, we show that a lentiviral JEV vector, expressing JEV prM and E proteins (TRIP/JEV.prME), but not JEV infection induces strong antibody-dependent enhancement (ADE) activities for infection of macrophages. Such antibodies strongly promoted infection via Fc receptors. ADE was found at both neutralizing and non-neutralizing serum dilutions. Nevertheless, in vivo JEV challenge of pigs demonstrated comparable protection induced by the TRIP/JEV.prME vaccine or heterologous JEV infection. Thus, either ADE antibodies cause no harm in the presence of neutralizing antibodies or may even have protective effects in vivo in pigs. Additionally, we found that both pre-infected and vaccinated pigs were not fully protected as low levels of viral RNA were found in lymphoid and nervous system tissue in some animals. Strikingly, the virus from the pre-infection persisted in the tonsils throughout the experiment. Finally, despite the vaccination challenge, viral RNA was detected in the oronasal swabs in all vaccinated pigs. These latter data are relevant when JEV vaccination is employed in pigs. PMID:28531165

Flaviviruses, an expanding threat in public health: focus on Dengue, West Nile, and Japanese encephalitis virus

PubMed Central

Daep, Carlo Amorin; Muñoz-Jordán, Jorge L.; Eugenin, Eliseo Alberto

2014-01-01

The flaviviruses Dengue, West Nile, and Japanese encephalitis represent three major mosquito-borne viruses worldwide. These pathogens impact the lives of millions of individuals and potentially could affect non-endemic areas already colonized by mosquito vectors. Unintentional transport of infected vectors (Aedes and Culex sp), traveling within endemic areas, rapid adaptation of the insects into new geographic locations, climate change, and lack of medical surveillance have greatly contributed to the increase in flaviviral infections worldwide. The mechanisms by which flaviviruses alter the immune and the central nervous system have only recently been examined despite the alarming number of infections, related deaths, and increasing global distribution. In this review, we will discuss the expansion of the geographic areas affected by flaviviruses, the potential threats to previously unaffected countries, the mechanisms of pathogenesis, and the potential therapeutic interventions to limit the devastating consequences of these viruses. PMID:25287260

Flaviviruses, an expanding threat in public health: focus on dengue, West Nile, and Japanese encephalitis virus.

PubMed

Daep, Carlo Amorin; Muñoz-Jordán, Jorge L; Eugenin, Eliseo Alberto

2014-12-01

The flaviviruses dengue, West Nile, and Japanese encephalitis represent three major mosquito-borne viruses worldwide. These pathogens impact the lives of millions of individuals and potentially could affect non-endemic areas already colonized by mosquito vectors. Unintentional transport of infected vectors (Aedes and Culex spp.), traveling within endemic areas, rapid adaptation of the insects into new geographic locations, climate change, and lack of medical surveillance have greatly contributed to the increase in flaviviral infections worldwide. The mechanisms by which flaviviruses alter the immune and the central nervous system have only recently been examined despite the alarming number of infections, related deaths, and increasing global distribution. In this review, we will discuss the expansion of the geographic areas affected by flaviviruses, the potential threats to previously unaffected countries, the mechanisms of pathogenesis, and the potential therapeutic interventions to limit the devastating consequences of these viruses.

Characterization of two mosquito STATs, AaSTAT and CtSTAT. Differential regulation of tyrosine phosphorylation and DNA binding activity by lipopolysaccharide treatment and by Japanese encephalitis virus infection.

PubMed

Lin, Chang-Chi; Chou, Chih-Ming; Hsu, Ya-Li; Lien, Jih-Ching; Wang, Yu-Ming; Chen, Shui-Tsung; Tsai, Shu-Chuan; Hsiao, Pei-Wen; Huang, Chang-Jen

2004-01-30

Two mosquito STATs, AaSTAT and CtSTAT, have been cloned from Aedes albopictus and Culex tritaeniorhynchus mosquitoes, respectively. These two STATs are more similar to those of Drosophila, Anopheles, and mammalian STAT5 in the DNA binding and Src homology 2 domains. The mRNA transcripts are expressed at all developmental stages, and the proteins are present predominantly at the pupal and adult stages in both mosquitoes. Stimulation with lipopolysaccharide resulted in an increase of tyrosine phosphorylation and DNA binding activity of AaSTAT and CtSTAT as well as an increase of luciferase activity of a reporter gene containing Drosophila STAT binding motif in mosquito C6/36 cells. After being infected with Japanese encephalitis virus, nuclear extracts of C6/36 cells revealed a decrease of tyrosine phosphorylation and DNA binding activity of AaSTAT which could be restored by sodium orthovanadate treatment. Taking all of the data together, this is the first report to clone and characterize two mosquito STATs with 81% identity and to demonstrate a different response of tyrosine phosphorylation and DNA binding of these two STATs by lipopolysaccharide treatment and by Japanese encephalitis virus infection.

Recent progress in West Nile virus diagnosis and vaccination

PubMed Central

2012-01-01

West Nile virus (WNV) is a positive-stranded RNA virus belonging to the Flaviviridae family, a large family with 3 main genera (flavivirus, hepacivirus and pestivirus). Among these viruses, there are several globally relevant human pathogens including the mosquito-borne dengue virus (DENV), yellow fever virus (YFV), Japanese encephalitis virus (JEV) and West Nile virus (WNV), as well as tick-borne viruses such as tick-borne encephalitis virus (TBEV). Since the mid-1990s, outbreaks of WN fever and encephalitis have occurred throughout the world and WNV is now endemic in Africa, Asia, Australia, the Middle East, Europe and the Unites States. This review describes the molecular virology, epidemiology, pathogenesis, and highlights recent progress regarding diagnosis and vaccination against WNV infections. PMID:22380523

CLEC5A Regulates Japanese Encephalitis Virus-Induced Neuroinflammation and Lethality

PubMed Central

Chen, Szu-Ting; Liu, Ren-Shyan; Wu, Ming-Fang; Lin, Yi-Ling; Chen, Se-Yi; Tan, David Tat-Wei; Chou, Teh-Ying; Tsai, I-Shuen; Li, Lei; Hsieh, Shie-Liang

2012-01-01

CLEC5A/MDL-1, a member of the myeloid C-type lectin family expressed on macrophages and neutrophils, is critical for dengue virus (DV)-induced hemorrhagic fever and shock syndrome in Stat1 −/− mice and ConA-treated wild type mice. However, whether CLEC5A is involved in the pathogenesis of viral encephalitis has not yet been investigated. To investigate the role of CLEC5A to regulate JEV-induced neuroinflammation, antagonistic anti-CLEC5A mAb and CLEC5A-deficient mice were generated. We find that Japanese encephalitis virus (JEV) directly interacts with CLEC5A and induces DAP12 phosphorylation in macrophages. In addition, JEV activates macrophages to secrete proinflammatory cytokines and chemokines, which are dramatically reduced in JEV-infected Clec5a−/− macrophages. Although blockade of CLEC5A cannot inhibit JEV infection of neurons and astrocytes, anti-CLEC5A mAb inhibits JEV-induced proinflammatory cytokine release from microglia and prevents bystander damage to neuronal cells. Moreover, JEV causes blood-brain barrier (BBB) disintegrity and lethality in STAT1-deficient (Stat1 −/−) mice, whereas peripheral administration of anti-CLEC5A mAb reduces infiltration of virus-harboring leukocytes into the central nervous system (CNS), restores BBB integrity, attenuates neuroinflammation, and protects mice from JEV-induced lethality. Moreover, all surviving mice develop protective humoral and cellular immunity against JEV infection. These observations demonstrate the critical role of CLEC5A in the pathogenesis of Japanese encephalitis, and identify CLEC5A as a target for the development of new treatments to reduce virus-induced brain damage. PMID:22536153

Quantification of vector and host competence and abundance for Japanese Encephalitis Virus: a systematic review of the literature.

USDA-ARS?s Scientific Manuscript database

Japanese encephalitis (JE) is a vector-borne disease caused by the Japanese encephalitis virus (JEV) that affects humans in Eastern and Southeastern Asia. Although it could be prevented by a vaccine, JE has no treatment and the inadvertent introduction of the virus into JEV-free countries, such as t...

Usutu virus: an emerging flavivirus in Europe.

PubMed

Ashraf, Usama; Ye, Jing; Ruan, Xindi; Wan, Shengfeng; Zhu, Bibo; Cao, Shengbo

2015-01-19

Usutu virus (USUV) is an African mosquito-borne flavivirus belonging to the Japanese encephalitis virus serocomplex. USUV is closely related to Murray Valley encephalitis virus, Japanese encephalitis virus, and West Nile virus. USUV was discovered in South Africa in 1959. In Europe, the first true demonstration of circulation of USUV was reported in Austria in 2001 with a significant die-off of Eurasian blackbirds. In the subsequent years, USUV expanded to neighboring countries, including Italy, Germany, Spain, Hungary, Switzerland, Poland, England, Czech Republic, Greece, and Belgium, where it caused unusual mortality in birds. In 2009, the first two human cases of USUV infection in Europe have been reported in Italy, causing meningoencephalitis in immunocompromised patients. This review describes USUV in terms of its life cycle, USUV surveillance from Africa to Europe, human cases, its cellular tropism and pathogenesis, its genetic relationship with other flaviviruses, genetic diversity among USUV strains, its diagnosis, and a discussion of the potential future threat to Asian countries.

Integrin αvβ3 promotes infection by Japanese encephalitis virus.

PubMed

Fan, Wenchun; Qian, Ping; Wang, Dandan; Zhi, Xianwei; Wei, Yanming; Chen, Huanchun; Li, Xiangmin

2017-04-01

Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus that is one of the major causes of viral encephalitis diseases worldwide. The JEV envelope protein facilitates viral entry, and its domain III contains an Arg-Gly-Asp (RGD) motif, that may modulate JEV entry through the RGD-binding integrin. In this study, the roles of integrin αv and β3 on the infection of JEV were evaluated. Reduced expression of integrin αv/β3 by special shRNA confers 2 to 4-fold inhibition of JEV replication in BHK-21 cells. Meanwhile, antibodies specific for integrin αv/β3 displayed ~58% and ~33% inhibition of JEV infectivity and RGD-specific peptides produced ~36% of inhibition. Expression of E protein and JEV RNA loads were clearly increased in CHO cells transfected with cDNA encoding human integrin β3. Moreover, integrin αv mediates JEV infection in viral binding stage of life cycle. Therefore, our study suggested that integrin αv and β3 serve as a host factor associated with JEV entry into the target cells. Copyright © 2016 Elsevier Ltd. All rights reserved.

Multi-Gene Detection and Identification of Mosquito-Borne RNA Viruses Using an Oligonucleotide Microarray

PubMed Central

Grubaugh, Nathan D.; McMenamy, Scott S.; Turell, Michael J.; Lee, John S.

2013-01-01

Background Arthropod-borne viruses are important emerging pathogens world-wide. Viruses transmitted by mosquitoes, such as dengue, yellow fever, and Japanese encephalitis viruses, infect hundreds of millions of people and animals each year. Global surveillance of these viruses in mosquito vectors using molecular based assays is critical for prevention and control of the associated diseases. Here, we report an oligonucleotide DNA microarray design, termed ArboChip5.1, for multi-gene detection and identification of mosquito-borne RNA viruses from the genera Flavivirus (family Flaviviridae), Alphavirus (Togaviridae), Orthobunyavirus (Bunyaviridae), and Phlebovirus (Bunyaviridae). Methodology/Principal Findings The assay utilizes targeted PCR amplification of three genes from each virus genus for electrochemical detection on a portable, field-tested microarray platform. Fifty-two viruses propagated in cell-culture were used to evaluate the specificity of the PCR primer sets and the ArboChip5.1 microarray capture probes. The microarray detected all of the tested viruses and differentiated between many closely related viruses such as members of the dengue, Japanese encephalitis, and Semliki Forest virus clades. Laboratory infected mosquitoes were used to simulate field samples and to determine the limits of detection. Additionally, we identified dengue virus type 3, Japanese encephalitis virus, Tembusu virus, Culex flavivirus, and a Quang Binh-like virus from mosquitoes collected in Thailand in 2011 and 2012. Conclusions/Significance We demonstrated that the described assay can be utilized in a comprehensive field surveillance program by the broad-range amplification and specific identification of arboviruses from infected mosquitoes. Furthermore, the microarray platform can be deployed in the field and viral RNA extraction to data analysis can occur in as little as 12 h. The information derived from the ArboChip5.1 microarray can help to establish public health priorities, detect disease outbreaks, and evaluate control programs. PMID:23967358

Japanese encephalitis - the prospects for new treatments.

PubMed

Turtle, Lance; Solomon, Tom

2018-04-26

Japanese encephalitis is a mosquito-borne disease that occurs in Asia and is caused by Japanese encephalitis virus (JEV), a member of the genus Flavivirus. Although many flaviviruses can cause encephalitis, JEV causes particularly severe neurological manifestations. The virus causes loss of more disability-adjusted life years than any other arthropod-borne virus owing to the frequent neurological sequelae of the condition. Despite substantial advances in our understanding of Japanese encephalitis from in vitro studies and animal models, studies of pathogenesis and treatment in humans are lagging behind. Few mechanistic studies have been conducted in humans, and only four clinical trials of therapies for Japanese encephalitis have taken place in the past 10 years despite an estimated incidence of 69,000 cases per year. Previous trials for Japanese encephalitis might have been too small to detect important benefits of potential treatments. Many potential treatment targets exist for Japanese encephalitis, and pathogenesis and virological studies have uncovered mechanisms by which these drugs could work. In this Review, we summarize the epidemiology, clinical features, prevention and treatment of Japanese encephalitis and focus on potential new therapeutic strategies, based on repurposing existing compounds that are already suitable for human use and could be trialled without delay. We use our newly improved understanding of Japanese encephalitis pathogenesis to posit potential treatments and outline some of the many challenges that remain in tackling the disease in humans.

Points to consider in the development of a surrogate for efficacy of novel Japanese encephalitis virus vaccines.

PubMed

Markoff, L

2000-05-26

Although an effective killed virus vaccine to prevent illness due to Japanese encephalitis virus (JEV) infection exists, many authorities recognize that a safe, effective live JEV vaccine is desirable in order to reduce the cost and the number of doses of vaccine required per immunization. A large-scale clinical efficacy trail for such a vaccine would be both unethical and impractical. Therefore, a surrogate for the efficacy of JE vaccines should be established. Detection of virus-neutralizing antibodies in sera of vaccinees could constitute such a surrogate for efficacy. Field studies of vaccinees in endemic areas and studies done in mice already exist to support this concept. Also, titers of virus-neutralizing antibodies are already accepted as a surrogate for the efficacy of yellow fever virus vaccines and for the efficacy of other viral vaccines as well. In developing a correlation between N antibody titers and protection from JEV infection, standard procedures must be validated and adopted for both measuring N antibodies and for testing in animals. A novel live virus vaccine could be tested in the mouse and/or the monkey model of JEV infection to establish a correlation between virus-neutralizing antibodies elicited by the vaccines and protection from encephalitis. In addition, sera of subjects receiving the novel live JEV vaccine in early clinical trials could be passively transferred to mice or monkeys in order to establish the protective immunogenicity of the vaccine in humans. A monkey model for JEV infection was recently established by scientists at WRAIR in the US. From this group, pools of JEV of known infectivity for Rhesus macaques may be obtained for testing of immunity elicited by live JE vaccine virus.

Replication of Japanese Encephalitis Virus.

DTIC Science & Technology

1980-12-10

persistently infected with JEV were studied. Over 200 cells were cloned from these cultures and all but four were nonproducers of infectious virus and viral...obtained for release of interfering particles by persis- tently infected cultures and clones , no new size classes of virus RNA could be demonstrated. iI...denaturing or non-dena- turing conditions. Both virus producer and non-producer cell clones were examined, and whether superinfected or not, they

Coltiviruses and Seadornaviruses in North America, Europe, and Asia

PubMed Central

Jaafar, Fauziah Mohd; de Micco, Philippe; de Lamballerie, Xavier

2005-01-01

Coltiviruses are tickborne viruses of the genus Coltivirus. The type species, Colorado tick fever virus (from North America), has been isolated from patients with flulike syndromes, meningitis, encephalitis, and other severe complications. Another coltivirus, Eyach virus, has been isolated from ticks in France and Germany and incriminated in febrile illnesses and neurologic syndromes. Seadornaviruses are endemic in Southeast Asia, particularly Indonesia and China. The prototype virus of the genus, Banna virus (BAV), has been isolated from many mosquito species, humans with encephalitis, pigs, and cattle. Two other seadornaviruses, Kadipiro and Liao Ning, were isolated only from mosquitoes. The epidemiology of seadornaviruses remains poorly documented. Evidence suggests that BAV is responsible for encephalitis in humans. Infection with BAV may be underreported because it circulates in regions with a high incidence of Japanese encephalitis and could be misdiagnosed as this disease. PMID:16318717

Japanese encephalitis in a French traveler to Nepal.

PubMed

Lagarde, S; Lagier, J-C; Charrel, R; Quérat, G; Vanhomwegen, J; Desprès, P; Pelletier, J; Kaphan, E

2014-02-01

Japanese encephalitis is frequent in Asia, with a severe prognosis, but rare in travelers. Culex mosquitoes transmit Japanese encephalitis virus. Risk factors are destination, duration of stay, summer and fall seasons, outdoor activities, and type of accommodation. We report the case of a French traveler to Nepal with neutralization-based serological confirmed Japanese encephalitis. He presented classical clinical (viral syndrome before an encephalitis status with behavioral disorder, global hypotonia, mutism, movement disorders, seizure, and coma), radiological (lesions of thalami, cortico-spinal tracts, and brainstem) and biological features (lymphocytic meningitis). Nowadays, the presence of Japanese encephalitis virus in Nepal, including mountain areas, is established but Japanese encephalitis remains rare in travelers returning from this area and neurologist physicians need to become familiar with this. We recommend vaccination for travelers spending a long period of time in Nepal and having at-risk outdoor activities.

Japanese encephalitis

PubMed Central

Yun, Sang-Im; Lee, Young-Min

2014-01-01

Japanese encephalitis (JE) is an infectious disease of the central nervous system caused by Japanese encephalitis virus (JEV), a zoonotic mosquito-borne flavivirus. JEV is prevalent in much of Asia and the Western Pacific, with over 4 billion people living at risk of infection. In the absence of antiviral intervention, vaccination is the only strategy to develop long-term sustainable protection against JEV infection. Over the past half-century, a mouse brain-derived inactivated vaccine has been used internationally for active immunization. To date, however, JEV is still a clinically important, emerging, and re-emerging human pathogen of global significance. In recent years, production of the mouse brain-derived vaccine has been discontinued, but 3 new cell culture-derived vaccines are available in various parts of the world. Here we review current aspects of JEV biology, summarize the 4 types of JEV vaccine, and discuss the potential of an infectious JEV cDNA technology for future vaccine development. PMID:24161909

Shedding of Japanese Encephalitis Virus in Oral Fluid of Infected Swine.

PubMed

Lyons, Amy C; Huang, Yan-Jang S; Park, So Lee; Ayers, Victoria B; Hettenbach, Susan M; Higgs, Stephen; McVey, D Scott; Noronha, Leela; Hsu, Wei-Wen; Vanlandingham, Dana L

2018-05-09

Japanese encephalitis virus (JEV) is a zoonotic mosquito-borne flavivirus endemic in the Asia-Pacific region. Maintenance of JEV in nature involves enzootic transmission by competent Culex mosquitoes among susceptible avian and swine species. Historically, JEV has been regarded as one of the most important arthropod-borne viruses in Southeast Asia. Oronasal shedding of JEV from infected amplification hosts was not recognized until the recent discovery of vector-free transmission of JEV among domestic pigs. In this study, oral shedding of JEV was characterized in domestic pigs and miniature swine representing the feral phenotype. A rope-based sampling method followed by the detection of viral RNA using RT-qPCR allowed the collection and detection of JEV in oral fluid samples collected from intradermally challenged animals. The results suggest that the shedding of JEV in oral fluid can be readily detected by molecular diagnostic assays at the acute phase of infection. It also demonstrates the feasibility of this technique for the diagnosis and surveillance of JEV in swine species.

Recombinant Measles AIK-C Vaccine Strain Expressing the prM-E Antigen of Japanese Encephalitis Virus.

PubMed

Higuchi, Akira; Toriniwa, Hiroko; Komiya, Tomoyoshi; Nakayama, Tetsuo

2016-01-01

An inactivated Japanese encephalitis virus (JEV) vaccine, which induces neutralizing antibodies, has been used for many years in Japan. In the present study, the JEV prM-E protein gene was cloned, inserted at the P/M junction of measles AIK-C cDNA, and an infectious virus was recovered. The JEV E protein was expressed in B95a cells infected with the recombinant virus. Cotton rats were inoculated with recombinant virus. Measles PA antibodies were detected three weeks after immunization. Neutralizing antibodies against JEV developed one week after inoculation, and EIA antibodies were detected three weeks after immunization. The measles AIK-C-based recombinant virus simultaneously induced measles and JEV immune responses, and may be a candidate for infant vaccines. Therefore, the present strategy of recombinant viruses based on a measles vaccine vector would be applicable to the platform for vaccine development.

Quantification of vector and host competence for Japanese encephalitis virus: a systematic review of the literature

USDA-ARS?s Scientific Manuscript database

Japanese encephalitis virus (JEV) is a virus of the Flavivirus genus that may result in encephalitis in human hosts. This vector-borne zoonosis occurs in Eastern and Southeastern Asia and an intentional or inadvertent introduction into the United States (US) will have major public health and economi...

Surveillance of Japanese Encephalitis Virus Infection in Mosquitoes in Vietnam from 2006 to 2008

PubMed Central

Kuwata, Ryusei; Nga, Phan Thi; Yen, Nguyen Thi; Hoshino, Keita; Isawa, Haruhiko; Higa, Yukiko; Hoang, Nguyen Vet; Trang, Bui Minh; Loan, Do Phuong; Phong, Tran Vu; Sasaki, Toshinori; Tsuda, Yoshio; Kobayashi, Mutsuo; Sawabe, Kyoko; Takagi, Masahiro

2013-01-01

Japanese encephalitis virus (JEV) infection in mosquitoes was monitored in Vietnam from 2006 to 2008. A total of 15,225 mosquitoes, identified as 26 species in five genera were collected and 12,621 were grouped into 447 pools for examination of JEV infection by assays for cytopathic effects in C6/36 cells and by RT-PCR to detect flavivirus RNA. Three JEV strains were isolated from Culex tritaeniorhynchus Giles collected in northern and southern Vietnam and two JEV strains were isolated from Culex vishnui Theobald collected in the highlands of Vietnam. Genetic and phylogenetic analyses, based on complete E gene nucleotide sequences, revealed that the five JEV strains were classified into the genotype I group and six amino acid differences were found in these five strains. These results indicated that multiple JEV genotype I populations are circulating countrywide in Vietnam, transmitted by bites of their Cx. tritaeniorhynchus and Cx. vishnui. PMID:23358634

Chandipura virus infection causing encephalitis in a tribal population of Odisha in eastern India.

PubMed

Dwibedi, Bhagirathi; Sabat, Jyotsnamayee; Hazra, Rupenangshu K; Kumar, Anu; Dinesh, Diwakar Singh; Kar, Shantanu K

2015-01-01

The sudden death of 10 children in a tribal village of Kandhamal district, Odisha in eastern India led to this investigation. We conducted a door-to-door survey to identify cases. Antibodies for Chandipura, Japanese encephalitis, dengue, chikungunya and West Nile viruses were tested by ELISA in probable cases. Chandipura virus RNA was tested from both human blood samples and sand flies by reverse transcriptase polymerase chain reaction. We conducted vector surveys in domestic and peridomestic areas, and collected sand flies. Entomological investigations revealed the presence of Phlebotomus argentipes and Sergentomiya sp. Thirty-five patients presented with fever, 12 of them had altered sensorium including 4 who had convulsions. The blood samples of 21 patients were tested; four samples revealed Chandipura virusspecific IgM antibody. Chandipura virus infection causing encephalitis affected this tribal population in eastern India at 1212 m above sea level. Copyright 2015, NMJI.

A systematic review of the literature to identify and quantify host and vector competence and abundance of Japanese Encephalitis Virus

USDA-ARS?s Scientific Manuscript database

Japanese Encephalitis virus (JEV) is a mosquito-borne arbovirus that causes endemic and epidemic encephalitis in Eastern and Southeastern Asia. Swine and wading birds serve as reservoirs for the virus, which can be transmitted to humans via mosquitos. Currently, there is no specific treatment availa...

Utility of Japanese encephalitis virus subgenomic replicon-based single-round infectious particles as antigens in neutralization tests for Zika virus and three other flaviviruses.

PubMed

Yamanaka, Atsushi; Moi, Meng Ling; Takasaki, Tomohiko; Kurane, Ichiro; Matsuda, Mami; Suzuki, Ryosuke; Konishi, Eiji

2017-05-01

The introduction of a foreign virus into an area may cause an outbreak, as with the Zika virus (ZIKV) outbreak in the Americas. Preparedness for handling a viral outbreak involves the development of tests for the serodiagnosis of foreign virus infections. We previously established a gene-based technology to generate some flaviviral antigens useful for functional antibody assays. The technology utilizes a Japanese encephalitis virus subgenomic replicon to generate single-round infectious particles (SRIPs) that possess designed surface antigens. In the present study, we successfully expanded the capacity of SRIPs to four human-pathogenic mosquito-borne flaviviruses that could potentially be introduced from endemic to non-endemic countries: ZIKV, Sepik virus, Wesselsbron virus, and Usutu virus. Flavivirus-crossreactive monoclonal antibodies dose-dependently neutralized these SRIPs. ZIKV-SRIPs also produced antibody-dose-dependent neutralization curves equivalent to those shown by authentic ZIKV particles using sera from a Zika fever patient. The faithful expression of designed surface antigens on SRIPs will allow their use in neutralization tests to diagnose foreign flaviviral infections. Copyright © 2017 Elsevier B.V. All rights reserved.

Vaccination against mosquito borne viral infections: current status.

PubMed

Wiwanitkit, Viroj

2007-12-01

Mosquito borne infectious diseases are among important group of diseases worldwide. Vaccination is available for some tropical mosquito-borne diseases, especially for Japanese encephalitis virus infection and yellow fever. There are also several attempts to develop new vaccines for the other mosquito-borne diseases such as malaria, dengue infection and West Nile virus infection. In this article, the author reviews the issues on vaccination of some important tropical mosquito borne infectious diseases.

Japanese encephalitis virus replicon-based vaccine expressing enterovirus-71 epitope confers dual protection from lethal challenges.

PubMed

Huang, Yi-Ting; Liao, Jia-Teh; Yen, Li-Chen; Chang, Yung-Kun; Lin, Yi-Ling; Liao, Ching-Len

2015-09-11

To construct safer recombinant flavivirus vaccine, we exploited Japanese encephalitis virus (JEV) replicon-based platform to generate single-round infectious particles (SRIPs) that expressed heterologous neutralizing epitope SP70 derived from enterovirus-71 (EV71). Such pseudo-infectious virus particles, named SRIP-SP70, although are not genuine viable viruses, closely mimic live virus infection to elicit immune responses within one round of viral life cycle. We found that, besides gaining of full protection to thwart JEV lethal challenge, female outbred ICR mice, when were immunized with SRIP-SP70 by prime-boost protocol, could not only induce SP70-specific and IgG2a predominant antibodies but also provide their newborns certain degree of protection against EV71 lethal challenge. Our results therefore exemplify that this vaccination strategy could indeed confer an immunized host a dual protective immunity against subsequent lethal challenge from JEV or EV71.

Meta-analyses of the proportion of Japanese encephalitis virus infection in vectors and vertebrate hosts.

PubMed

Oliveira, Ana R S; Cohnstaedt, Lee W; Strathe, Erin; Hernández, Luciana Etcheverry; McVey, D Scott; Piaggio, José; Cernicchiaro, Natalia

2017-09-07

Japanese encephalitis (JE) is a zoonosis in Southeast Asia vectored by mosquitoes infected with the Japanese encephalitis virus (JEV). Japanese encephalitis is considered an emerging exotic infectious disease with potential for introduction in currently JEV-free countries. Pigs and ardeid birds are reservoir hosts and play a major role on the transmission dynamics of the disease. The objective of the study was to quantitatively summarize the proportion of JEV infection in vectors and vertebrate hosts from data pertaining to observational studies obtained in a systematic review of the literature on vector and host competence for JEV, using meta-analyses. Data gathered in this study pertained to three outcomes: proportion of JEV infection in vectors, proportion of JEV infection in vertebrate hosts, and minimum infection rate (MIR) in vectors. Random-effects subgroup meta-analysis models were fitted by species (mosquito or vertebrate host species) to estimate pooled summary measures, as well as to compute the variance between studies. Meta-regression models were fitted to assess the association between different predictors and the outcomes of interest and to identify sources of heterogeneity among studies. Predictors included in all models were mosquito/vertebrate host species, diagnostic methods, mosquito capture methods, season, country/region, age category, and number of mosquitos per pool. Mosquito species, diagnostic method, country, and capture method represented important sources of heterogeneity associated with the proportion of JEV infection; host species and region were considered sources of heterogeneity associated with the proportion of JEV infection in hosts; and diagnostic and mosquito capture methods were deemed important contributors of heterogeneity for the MIR outcome. Our findings provide reference pooled summary estimates of vector competence for JEV for some mosquito species, as well as of sources of variability for these outcomes. Moreover, this work provides useful guidelines when interpreting vector and host infection proportions or prevalence from observational studies, and contributes to further our understanding of vector and vertebrate host competence for JEV, elucidating information on the relative importance of vectors and hosts on JEV introduction and transmission.

Characterization of a novel insect-specific flavivirus from Brazil: Potential for inhibition of infection of arthropod cells with medically important flaviviruses.

DOE PAGES

Kenney, Joan L.; Solberg, Owen D.; Langevin, Stanley A.; ...

2014-01-12

In the past decade, there has been an upsurge in the number of newly described insect-specific flaviviruses isolated pan-globally. We recently described the isolation of a novel flavivirus (tentatively designated ‘Nhumirim virus’; NHUV) that represents an example of a unique subset of apparently insect-specific viruses that phylogenetically affiliate with dual-host mosquito-borne flaviviruses despite appearing to be limited to replication in mosquito cells. We characterized the in vitro growth potential and 3' untranslated region (UTR) sequence homology with alternative flaviviruses, and evaluated the virus’s capacity to suppress replication of representative Culex spp.-vectored pathogenic flaviviruses in mosquito cells. Only mosquito cell linesmore » were found to support NHUV replication, further reinforcing the insect-specific phenotype of this virus. Analysis of the sequence and predicted RNA secondary structures of the 3' UTR indicated NHUV to be most similar to viruses within the yellow fever serogroup and Japanese encephalitis serogroup, and viruses in the tick-borne flavivirus clade. NHUV was found to share the fewest conserved sequence elements when compared with traditional insect-specific flaviviruses. This suggests that, despite apparently being insect specific, this virus probably diverged from an ancestral mosquito-borne flavivirus. Co-infection experiments indicated that prior or concurrent infection of mosquito cells with NHUV resulted in a significant reduction in virus production of West Nile virus (WNV), St Louis encephalitis virus (SLEV) and Japanese encephalitis virus. As a result, the inhibitory effect was most effective against WNV and SLEV with over a 106-fold and 104-fold reduction in peak titres, respectively.« less

Characterization of a novel insect-specific flavivirus from Brazil: Potential for inhibition of infection of arthropod cells with medically important flaviviruses.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kenney, Joan L.; Solberg, Owen D.; Langevin, Stanley A.

In the past decade, there has been an upsurge in the number of newly described insect-specific flaviviruses isolated pan-globally. We recently described the isolation of a novel flavivirus (tentatively designated ‘Nhumirim virus’; NHUV) that represents an example of a unique subset of apparently insect-specific viruses that phylogenetically affiliate with dual-host mosquito-borne flaviviruses despite appearing to be limited to replication in mosquito cells. We characterized the in vitro growth potential and 3' untranslated region (UTR) sequence homology with alternative flaviviruses, and evaluated the virus’s capacity to suppress replication of representative Culex spp.-vectored pathogenic flaviviruses in mosquito cells. Only mosquito cell linesmore » were found to support NHUV replication, further reinforcing the insect-specific phenotype of this virus. Analysis of the sequence and predicted RNA secondary structures of the 3' UTR indicated NHUV to be most similar to viruses within the yellow fever serogroup and Japanese encephalitis serogroup, and viruses in the tick-borne flavivirus clade. NHUV was found to share the fewest conserved sequence elements when compared with traditional insect-specific flaviviruses. This suggests that, despite apparently being insect specific, this virus probably diverged from an ancestral mosquito-borne flavivirus. Co-infection experiments indicated that prior or concurrent infection of mosquito cells with NHUV resulted in a significant reduction in virus production of West Nile virus (WNV), St Louis encephalitis virus (SLEV) and Japanese encephalitis virus. As a result, the inhibitory effect was most effective against WNV and SLEV with over a 106-fold and 104-fold reduction in peak titres, respectively.« less

Antibodies to H5 subtype avian influenza virus and Japanese encephalitis virus in northern pintails (Anas acuta) sampled in Japan

USDA-ARS?s Scientific Manuscript database

Blood samples from 105 northern pintails (Anas acuta) captured on Hokkaido, Japan were tested for antibodies to avian influenza virus (AIV), Japanese encephalitis virus (JEV) and West Nile virus (WNV) to assess possible involvement of this species in the transmission and spread of economically impor...

Japanese encephalitis virus NS1' protein depends on pseudoknot secondary structure and is cleaved by caspase during virus infection and cell apoptosis.

PubMed

Sun, Jin; Yu, Yongxin; Deubel, Vincent

2012-09-01

Japanese encephalitis virus (JEV) is a flavivirus with a complex life cycle involving mosquito vectors that mainly target birds and pigs, and causes severe encephalitis in children in Asia. Neurotropic flaviviruses of the JEV serogroup have a particular characteristic of expressing a unique nonstructural NS1' protein, which is a prolongation of NS1 at the C terminus by 52 amino acids derived from a pseudoknot-driven-1 translation frameshift. Protein NS1' is associated with virus neuro-invasiveness. In this study, the need of the pseudoknot structure for NS1' synthesis was confirmed. By using a specific antibody against the prolonged peptide, NS1' was found to be absent from the JEV SA14-14-2 vaccine strain, resulting from a single nucleotide silent mutation in the pseudoknot. A partial cleavage of NS1' at a specific site of its C-terminal appendix recognized by caspases and inhibited by caspase inhibitors suggests a unique feature of intracellular NS1'. Copyright © 2012 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Detection and isolation of Japanese encephalitis virus from blood clots collected during the acute phase of infection.

PubMed

Sapkal, Gajanan N; Wairagkar, Nitin S; Ayachit, Vijay M; Bondre, Vijay P; Gore, Milind M

2007-12-01

Clinical specimens from an encephalitis outbreak in the Lakhimpur area of Uttar Pradesh, India, were investigated for identification and characterization of the etiologic agent. IgM capture ELISA showed recent Japanese encephalitis virus (JEV) infection. JEV isolation was attempted from white blood cells (WBCs) separated from blood clots of 12 patients (9 IgM positive and 3 negative) by serial co-culturing with phytohemagglutinin P-stimulated peripheral blood mononuclear leukocytes (PBMCs) obtained from pre-screened JEV sero-negative healthy individuals. JEV was isolated from two IgM-positive blood clots. Isolate 014178 was detected in WBCs and in the first passage of PBMCs by ELISA and reverse transcriptase-polymerase chain reaction. Isolate 014173 was detectable only after a second passage in PBMC co-culture. Sequence analysis of 346 nt of the C-prM region showed homology with JEV strain GP78. This is the first report on isolation of JEV from patient blood clots. Our study shows that the co-cultures of PBMCs separated from patient blood clots provide an additional source for JEV isolation.

Characterization of a novel insect-specific flavivirus from Brazil: potential for inhibition of infection of arthropod cells with medically important flaviviruses

PubMed Central

Kenney, Joan L.; Solberg, Owen D.; Langevin, Stanley A.; Brault, Aaron C.

2015-01-01

In the past decade there has been an upsurge in the number of newly described insect-specific flaviviruses isolated pan-globally. We recently described the isolation of a novel flavivirus (tentatively designated “Nhumirim virus”; NHUV) (Pauvolid-Correa et al., in review) that represents an example of a unique subset of apparently insect-specific viruses that phylogenetically affiliate with dual-host mosquito-borne flaviviruses despite appearing to be limited to replication in mosquito cells. We characterized the in vitro growth potential, 3’ untranslated region (UTR) sequence homology with alternative flaviviruses, and evaluated the virus’s capacity to suppress replication of representative Culex spp. vectored pathogenic flaviviruses in mosquito cells. Only mosquito cell lines were found to support NHUV replication, further reinforcing the insect-specific phenotype of this virus. Analysis of the sequence and predicted RNA secondary structures of the 3’ UTR indicate NHUV to be most similar to viruses within the yellow fever serogroup, Japanese encephalitis serogroup, and viruses in the tick-borne flavivirus clade. NHUV was found to share the fewest conserved sequence elements when compared to traditional insect-specific flaviviruses. This suggests that, despite being apparently insect-specific, this virus likely diverged from an ancestral mosquito-borne flavivirus. Co-infection experiments indicated that prior or concurrent infection of mosquito cells with NHUV resulted in significant reduction in viral production of West Nile virus (WNV), St. Louis encephalitis virus (SLEV) and Japanese encephalitis virus. The inhibitory effect was most effective against WNV and SLEV with over a million-fold and 10,000-fold reduction in peak titers, respectively. PMID:25146007

Involvement of cyclophilin B in the replication of Japanese encephalitis virus.

PubMed

Kambara, Hiroto; Tani, Hideki; Mori, Yoshio; Abe, Takayuki; Katoh, Hiroshi; Fukuhara, Takasuke; Taguwa, Shuhei; Moriishi, Kohji; Matsuura, Yoshiharu

2011-03-30

Japanese encephalitis virus (JEV) is a mosquito-borne RNA virus that belongs to the Flaviviridae family. In this study, we have examined the effect of cyclosporin A (CsA) on the propagation of JEV. CsA exhibited potent anti-JEV activity in various mammalian cell lines through the inhibition of CypB. The propagation of JEV was impaired in the CypB-knockdown cells and this reduction was cancelled by the expression of wild-type but not of peptidylprolyl cis-trans isomerase (PPIase)-deficient CypB, indicating that PPIase activity of CypB is critical for JEV propagation. Infection of pseudotype viruses bearing JEV envelope proteins was not impaired by the knockdown of CypB, suggesting that CypB participates in the replication but not in the entry of JEV. CypB was colocalized and immunoprecipitated with JEV NS4A in infected cells. These results suggest that CypB plays a crucial role in the replication of JEV through an interaction with NS4A. Copyright © 2011 Elsevier Inc. All rights reserved.

Pathogenic and Genotypic Characterization of a Japanese Encephalitis Virus Isolate Associated with Reproductive Failure in an Indian Pig Herd

PubMed Central

Desingu, P. A.; Ray, Pradeep K.; Patel, B. H. M.; Singh, R.; Singh, R. K.; Saikumar, G

2016-01-01

Background India is endemic to Japanese encephalitis virus (JEV) and recurrent outbreaks occur mainly in rice growing areas. Pigs are considered to be the amplifying host for JEV and infection in gestating pigs results in reproductive failure. Most studies conducted on JEV infection in Indian pigs have been serological surveys and very little is known about JEV genotypes circulating in pigs. So the potential risk posed by pigs in JEV transmission and the genetic relationship between viruses circulating in pigs, mosquitoes and humans is poorly understood. Methodology/Principal Findings This study was conducted in pigs with a history of reproductive failure characterized by stillborn piglets with neuropathological lesions. Japanese encephalitis (JE) suspected brain specimens inoculated intracerebrally into mice and Vero cells resulted in successful isolation of JEV/SW/IVRI/395A/2014. Clinicopathological observations in infected mice, demonstration of JEV antigen in brain, and analysis of the envelope protein identified the swine isolate as being neurovirulent. Phylogenetic analysis based on prM and E gene sequences showed that it belonged to genotype III. This swine isolate was closely related to JEV associated with the 2005 outbreak in India and JaoArS982 from Japan. Phylogenetic analysis of JEV strains collected between 1956 and 2014 in India categorized the GIII viruses into different clades blurring their spatial distribution, which has been discernible in the previous century. Conclusions/Significance Isolation of JEV from stillborn piglets and its close genetic relationship with viruses detected at least three decades ago in humans and mosquitoes in Japan suggests that the virus may have been circulating among Indian pigs for several decades. The close similarity between the present swine isolate and those detected in humans affected in the 2005 outbreak in Uttar Pradesh, India, suggests the need for more intensive surveillance of pigs and implementation of suitable strategies to control JE in India. PMID:26895440

Japanese encephalitis virus infection, diagnosis and control in domestic animals.

PubMed

Mansfield, Karen L; Hernández-Triana, Luis M; Banyard, Ashley C; Fooks, Anthony R; Johnson, Nicholas

2017-03-01

Japanese encephalitis virus (JEV) is a significant cause of neurological disease in humans throughout Asia causing an estimated 70,000 human cases each year with approximately 10,000 fatalities. The virus contains a positive sense RNA genome within a host-derived membrane and is classified within the family Flaviviridae. Like many flaviviruses, it is transmitted by mosquitoes, particularly those of the genus Culex in a natural cycle involving birds and some livestock species. Spill-over into domestic animals results in a spectrum of disease ranging from asymptomatic infection in some species to acute neurological signs in others. The impact of JEV infection is particularly apparent in pigs. Although infection in adult swine does not result in symptomatic disease, it is considered a significant reproductive problem causing abortion, still-birth and birth defects. Infected piglets can display fatal neurological disease. Equines are also infected, resulting in non-specific signs including pyrexia, but occasionally leading to overt neurological disease that in extreme cases can lead to death. Veterinary vaccination is available for both pigs and horses. This review of JEV disease in livestock considers the current diagnostic techniques available for detection of the virus. Options for disease control and prevention within the veterinary sector are discussed. Such measures are critical in breaking the link to zoonotic transmission into the human population where humans are dead-end hosts. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Research in drug development against viral diseases of military importance (biological testing). Volume 2. Final report, 15 November 1985-31 January 1991

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shannon, W.M.; Arnett, G.; Brazier, A.D.

1991-03-01

The purpose of this program is to evaluate the efficacy of candidate antiviral compounds against a spectrum of viruses of military importance. This program involves (a) primary testing of chemical compounds and natural products for antiviral efficacy in vitro using standard CPE-inhibition assays, (b) primary testing of compounds for antiviral efficacy in vivo in animal model systems, and (c) secondary evaluation of the active candidate antiviral compounds. The target viruses for in vitro testing are Vaccinia Virus (VV), Adenovirus (AD2), Vesicular Stomatitis Virus (VSV), Punta Toro Virus (PT), Sandfly fever Virus (SF), Yellow Fever Virus (YF), Venezuelan Equine Encephalomyelitis Virusmore » (VE), Japanese Encephalitis Virus, Pichinde Virus (PIC), Hantaan Virus (HTN), and Human Immunodeficiency Virus (HIV). The in vivo systems are Pichinde Virus infection of hamsters, Venezuelan Equine Encephalomyelitis Virus, Japanese Encephalitis Virus and Vaccinia virus infections of mice. Approximately 10,000 compounds have been received for in vitro evaluation and over 66,000 assays have been performed on this contract. Compounds have been identified in nearly all virus systems that have confirmed antiviral activity equal or exceeding that of the various positive control compounds (ribavirin, selenazofurin, carbocyclic-3-aza-adenosine, adenosine dialdehyde, Ara-A, ddC and AZT). Many of these compounds represent potent and selective new antiviral agents.« less

Serosurveillance for Japanese encephalitis and West Nile viruses in resident birds in Hawai'i.

PubMed

Nemeth, Nicole M; Bosco-Lauth, Angela M; Sciulli, Rebecca H; Gose, Remedios B; Nagata, Mark T; Bowen, Richard A

2010-04-01

Japanese encephalitis virus (JEV) and West Nile virus (WNV) are emerging zoonotic arboviruses that have recently undergone intercontinental expansion. Both JEV and WNV are naturally transmitted between mosquito vectors and vertebrate reservoir hosts, including birds. A potential route of JEV introduction from Asia to western North America is via the Hawaiian archipelago, while the spread of WNV from mainland North America to Hawai'i is also considered an impending threat. We surveyed resident, non-native bird sera for antibodies to JEV and WNV on two Hawaiian Islands from 2004-2005. Three of 1,835 birds (0.16%) had evidence of antiflavivirus antibodies, demonstrating neutralizing activity to JEV and St. Louis encephalitis virus (SLEV). These detections could represent a limited transmission focus of either, or both, JEV and SLEV, or cross-reactive antibodies due to primary infection with an alternate flavivirus. Frequent air traffic from both Asia and North America to Hawai'i, along with the presence of probable competent vectors and amplifying vertebrate hosts in Hawai'i, increases the likelihood of introduction and maintenance of novel flaviviruses. Therefore, it is important to monitor for the presence of these viruses.

Rab5 and Rab11 Are Required for Clathrin-Dependent Endocytosis of Japanese Encephalitis Virus in BHK-21 Cells.

PubMed

Liu, Chun-Chun; Zhang, Yun-Na; Li, Zhao-Yao; Hou, Jin-Xiu; Zhou, Jing; Kan, Lin; Zhou, Bin; Chen, Pu-Yan

2017-10-01

During infection Japanese encephalitis virus (JEV) generally enters host cells via receptor-mediated clathrin-dependent endocytosis. The trafficking of JEV within endosomes is controlled by Rab GTPases, but which Rab proteins are involved in JEV entry into BHK-21 cells is unknown. In this study, entry and postinternalization of JEV were analyzed using biochemical inhibitors, RNA interference, and dominant negative (DN) mutants. Our data demonstrate that JEV entry into BHK-21 cells depends on clathrin, dynamin, and cholesterol but not on caveolae or macropinocytosis. The effect on JEV infection of dominant negative (DN) mutants of four Rab proteins that regulate endosomal trafficking was examined. Expression of DN Rab5 and DN Rab11, but not DN Rab7 and DN Rab9, significantly inhibited JEV replication. These results were further tested by silencing Rab5 or Rab11 expression before viral infection. Confocal microscopy showed that virus particles colocalized with Rab5 or Rab11 within 15 min after virus entry, suggesting that after internalization JEV moves to early and recycling endosomes before the release of the viral genome. Our findings demonstrate the roles of Rab5 and Rab11 on JEV infection of BHK-21 cells through the endocytic pathway, providing new insights into the life cycle of flaviviruses. IMPORTANCE Although Japanese encephalitis virus (JEV) utilizes different endocytic pathways depending on the cell type being infected, the detailed mechanism of its entry into BHK-21 cells is unknown. Understanding the process of JEV endocytosis and postinternalization will advance our knowledge of JEV infection and pathogenesis as well as provide potential novel drug targets for antiviral intervention. With this objective, we used systematic approaches to dissect this process. The results show that entry of JEV into BHK-21 cells requires a low-pH environment and that the process occurs through dynamin-, actin-, and cholesterol-dependent clathrin-mediated endocytosis that requires Rab5 and Rab11. Our work provides a detailed picture of the entry of JEV into BHK-21 cells and the cellular events that follow. Copyright © 2017 American Society for Microbiology.

GRP78 Is an Important Host Factor for Japanese Encephalitis Virus Entry and Replication in Mammalian Cells.

PubMed

Nain, Minu; Mukherjee, Sriparna; Karmakar, Sonali Porey; Paton, Adrienne W; Paton, James C; Abdin, M Z; Basu, Anirban; Kalia, Manjula; Vrati, Sudhanshu

2017-03-15

Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, is the leading cause of viral encephalitis in Southeast Asia with potential to become a global pathogen. Here, we identify glucose-regulated protein 78 (GRP78) as an important host protein for virus entry and replication. Using the plasma membrane fractions from mouse neuronal (Neuro2a) cells, mass spectroscopy analysis identified GRP78 as a protein interacting with recombinant JEV envelope protein domain III. GRP78 was found to be expressed on the plasma membranes of Neuro2a cells, mouse primary neurons, and human epithelial Huh-7 cells. Antibodies against GRP78 significantly inhibited JEV entry in all three cell types, suggesting an important role of the protein in virus entry. Depletion of GRP78 by small interfering RNA (siRNA) significantly blocked JEV entry into Neuro2a cells, further supporting its role in virus uptake. Immunofluorescence studies showed extensive colocalization of GRP78 with JEV envelope protein in virus-infected cells. This interaction was also confirmed by immunoprecipitation studies. Additionally, GRP78 was shown to have an important role in JEV replication, as treatment of cells post-virus entry with subtilase cytotoxin that specifically cleaved GRP78 led to a substantial reduction in viral RNA replication and protein synthesis, resulting in significantly reduced extracellular virus titers. Our results indicate that GRP78, an endoplasmic reticulum chaperon of the HSP70 family, is a novel host factor involved at multiple steps of the JEV life cycle and could be a potential therapeutic target. IMPORTANCE Recent years have seen a rapid spread of mosquito-borne diseases caused by flaviviruses. The flavivirus family includes West Nile, dengue, Japanese encephalitis, and Zika viruses, which are major threats to public health with potential to become global pathogens. JEV is the major cause of viral encephalitis in several parts of Southeast Asia, affecting a predominantly pediatric population with a high mortality rate. This study is focused on identification of crucial host factors that could be targeted to cripple virus infection and ultimately lead to development of effective antivirals. We have identified a cellular protein, GRP78, that plays a dual role in virus entry and virus replication, two crucial steps of the virus life cycle, and thus is a novel host factor that could be a potential therapeutic target. Copyright © 2017 American Society for Microbiology.

Modulation of the immune-related gene responses to protect mice against Japanese encephalitis virus using the antimicrobial peptide, tilapia hepcidin 1-5.

PubMed

Huang, Han-Ning; Rajanbabu, Venugopal; Pan, Chieh-Yu; Chan, Yi-Lin; Hui, Cho-Fat; Chen, Jyh-Yih; Wu, Chang-Jer

2011-10-01

Japanese encephalitis virus (JEV), a neurotropic flavivirus, is one of the major causes of acute encephalitis in humans. After infection, it is commonly associated with inflammatory reactions and neurological disease. There is still no effective antiviral drug available against Japanese encephalitis virus infection. Recently, a number of investigators found that antimicrobial peptide (AMPs) present a broad range of biological activities including antimicrobial and immunomodulatory activities. In this study, we found that an AMP, tilapia hepcidin (TH)1-5, caused no harm to either cells or test animals during the test course and could control JEV viral infection in BHK-21 cells. Mice co-injected with TH1-5/JEV and subsequently subjected to JEV re-challenge survived and behaved normally. The neuroprotective effects were associated with marked decreases in: (i) the viral load and viral replication within the brain, (ii) neuronal death, and (iii) secondary inflammation resulting from microglial activation. TH1-5 was also determined to enhance adaptive immunity by elevating levels of anti-JEV-neutralizing antibodies in the serum. The microarray data also showed that TH1-5 modulated Socs-6, interleukin (IL)-6, Toll-like receptor (TLR)-1, TLR-7, caspase-4, interferon (IFN)-β1, ATF-3, and several immune-responsive genes to protect mice against JEV infection. In addition, TH1-5 was confirmed to modulate the expressions of several proinflammatory and immune-responsive genes, such as IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, tumor necrosis factor (TNF)-α, IFN-γ and monocyte chemoattractant protein (MCP)-1 at both the transcriptional and translational levels in JEV-infected mice. In conclusion, our findings provide mechanistic insights into the actions of TH1-5 against JEV. Results from our in vivo and in vitro experiments clearly indicate that TH1-5 has antiviral, neuroprotective, anti-inflammatory, and immunomodulatory activities. Furthermore, TH1-5 successfully reduced the severity of disease induced by JEV. Our results point out that TH1-5 is a promising candidate for further development as an antiviral agent against JEV infection. Copyright © 2011 Elsevier Ltd. All rights reserved.

Inhibitory effect of the green tea molecule EGCG against dengue virus infection.

PubMed

Raekiansyah, Muhareva; Buerano, Corazon C; Luz, Mark Anthony D; Morita, Kouichi

2018-06-01

Dengue virus (DENV) infection is a major public health problem worldwide; however, specific antiviral drugs against it are not available. Hence, identifying effective antiviral agents for the prevention of DENV infection is important. In this study, we showed that the reportedly highly biologically active green-tea component epigallocatechin gallate (EGCG) inhibited dengue virus infection regardless of infecting serotype, but no or minimal inhibition was observed with other flaviviruses, including Japanese encephalitis virus, yellow fever virus, and Zika virus. EGCG exerted its antiviral effect mainly at the early stage of infection, probably by interacting directly with virions to prevent virus infection. Our results suggest that EGCG specifically targets DENV and might be used as a lead structure to develop an antiviral drug for use against the virus.

Emergence or improved detection of Japanese encephalitis virus in the Himalayan highlands?

PubMed Central

Baylis, Matthew; Barker, Christopher M.; Caminade, Cyril; Joshi, Bhoj R.; Pant, Ganesh R.; Rayamajhi, Ajit; Reisen, William K.; Impoinvil, Daniel E.

2016-01-01

The emergence of Japanese encephalitis virus (JEV) in the Himalayan highlands is of significant veterinary and public health concern and may be related to climate warming and anthropogenic landscape change, or simply improved surveillance. To investigate this phenomenon, a One Health approach focusing on the phylogeography of JEV, the distribution and abundance of the mosquito vectors, and seroprevalence in humans and animal reservoirs would be useful to understand the epidemiology of Japanese encephalitis in highland areas. PMID:26956778

Experimental therapies for yellow fever

PubMed Central

Julander, Justin G.

2013-01-01

A number of viruses in the family Flaviviridae are the focus of efforts to develop effective antiviral therapies. Success has been achieved with inhibitors for the treatment of hepatitis C, and there is interest in clinical trials of drugs against dengue fever. Antiviral therapies have also been evaluated in patients with Japanese encephalitis and West Nile encephalitis. However, no treatment has been developed against the prototype flavivirus, yellow fever virus (YFV). Despite the availability of the live, attenuated 17D vaccine, thousands of cases of YF continue to occur each year in Africa and South America, with a significant mortality rate. In addition, a small number of vaccinees develop severe systemic infections with the 17D virus. This paper reviews current efforts to develop antiviral therapies, either directly targeting the virus or blocking detrimental host responses to infection. PMID:23237991

Force Protection Technologies for the 2010-2020 Timeframe

DTIC Science & Technology

2003-11-01

virus V12. Monkey pox virus Viruses V13. Rift Valley fever virus V14. Tick-borne encephalitis virus (Russian Spring-Summer... virus Viruses V20. Japanese encephalitis virus R1. Coxiella burnetti R2. Bartonella Quintana (Rochlimea quintana, Rickettsia quintana) R3...fever virus WV5. Oropouche virus WV6. Powassan virus WV7. Rocio virus Viruses (Warning List) WV8. St Louis encephalitis virus WB1.

Seasonal abundance and potential of Japanese encephalitis virus infection in mosquitoes at the nesting colony of ardeid birds, Thailand.

PubMed

Changbunjong, Tanasak; Weluwanarak, Thekhawet; Taowan, Namaoy; Suksai, Parut; Chamsai, Tatiyanuch; Sedwisai, Poonyapat

2013-03-01

To investigate the abundance and seasonal dynamics of mosquitoes, and to detect Japanese encephalitis virus (JEV) in these mosquitoes at the nesting colony of ardeid birds. Mosquitoes were collected bimonthly from July 2009 to May 2010 by Centers for Disease Control. Light traps and dry ice, as a source of CO2, were employed to attract mosquitoes. Mosquitoes were first identified, pooled into groups of upto 50 mosquitoes by species, and tested for JEV infection by viral isolation and reverse transcriptase polymerase chain reaction. A total of 20 370 mosquitoes comprising 14 species in five genera were collected. The five most abundant mosquito species collected were Culex tritaeniorhynchus (95.46%), Culex vishnui (2.68%), Culex gelidus (0.72%), Anopheles peditaeniatus (0.58%) and Culex quinquefasciatus (0.22%). Mosquito peak densities were observed in July. All of 416 mosquito pools were negative for JEV. This study provides new information about mosquito species and status of JEV infection in mosquitoes in Thailand. Further study should be done to continue a close survey for the presence of this virus in the ardeid birds.

Susceptibility of a North American Culex quinquefasciatus to Japanese encephalitis virus

USDA-ARS?s Scientific Manuscript database

Japanese encephalitis virus (JEV) is a flavivirus that is transmitted by Culex (Cx.) tritaeniorhynchus in tropical and subtropical regions of Asia. The endemic transmission cycle involves domestic pigs and avian species that serve as amplification hosts; humans are incidental hosts that cannot devel...

Rapid Diagnosis of Arbovirus and Arenavirus Infections by Immunofluorescence.

DTIC Science & Technology

1981-01-01

in the indirect imunofluorescence test, have been prepared. The viruses in the slide were: lanai, Japanese encephalitis, Langat , Rocio and yellow fever... Langat , Rocio and yellow fever. The slides gave positive reactions when tested with hyperimmune mouse sera including 6 of 7 sera for viruses not...Nakayama; Langat , TP21; Pongola, MP 781; Rocio, San Paulo ; Sicilian phlebotomus fever, Sabin; West Nile, EgIO; yellow fever, Asibi. the viruses are

Japanese encephalitis.

PubMed

Morita, K; Nabeshima, T; Buerano, C C

2015-08-01

Japanese encephalitis (JE) is an inflammation of the central nervous system in humans and animals, specifically horses and cattle. The disease, which can sometimes be fatal, is caused by the flavivirus Japanese encephalitis virus (JEV), of which there are five genotypes (genotypes 1, 2, 3, 4 and 5). The transmission cycle of the virus involves pigs and wild birds as virus amplifiers and mosquitoes as vectors for transferring the virus between amplifying hosts and to dead- end hosts, i.e. humans, horses and cattle. In horses and cattle the disease is usually asymptomatic, but when clinical signs do occur they include fever, decreased appetite, frothing at the mouth, rigidity of the legs and recumbency, and neurological signs, such as convulsive fits, circling, marked depression and disordered consciousness. In pigs, it can cause abortion and stillbirths. At present, the virus is detected in a wide area covering eastern and southern Asia, Indonesia, northern Australia, Papua New Guinea and Pakistan. JEV RNA has also been detected in Italy, first in dead birds in 1997 and 2000 and then in mosquitoes in 2010. Genotype shift, i.e. a change of genotype from genotype 3 to genotype 1, has occurred in some countries, namely Japan, South Korea, Chinese Taipei and Vietnam. Laboratory methods are available for confirming the causative agent of the disease. There are control measures to prevent or minimise infection and, among them, vaccination is one of the most important and one which should be adopted in endemic and epidemic areas.

Epitope-blocking enzyme-linked immunosorbent assay to differentiate west nile virus from Japanese encephalitis virus infections in equine sera.

PubMed

Kitai, Yoko; Shoda, Mizue; Kondo, Takashi; Konishi, Eiji

2007-08-01

West Nile virus (WNV) is now widely distributed worldwide, except in most areas of Asia where Japanese encephalitis virus (JEV) is distributed. Considering the movement and migration of reservoir birds, there is concern that WNV may be introduced in Asian countries. Although manuals and guidelines for serological tests have been created in Japan in preparedness for the introduction of WNV, differential diagnosis between WNV and JEV may be complicated by antigenic cross-reactivities between these flaviviruses. Here, we generated a monoclonal antibody specific for the nonstructural protein 1 (NS1) of WNV and established an epitope-blocking enzyme-linked immunosorbent assay that can differentiate WNV from JEV infections in horse sera. Under conditions well suited for our assay system, samples collected from 95 horses in Japan (regarded as negative for WNV antibodies), including those collected from horses naturally infected with JEV, showed a mean inhibition value of 8.2% and a standard deviation (SD) of 6.5%. However, inhibition values obtained with serum used as a positive control (obtained after 28 days from a horse experimentally infected with WNV) in nine separate experiments showed a mean of 54.4% and an SD of 7.1%. We tentatively determined 27.6% (mean + 3 x SD obtained with 95 negative samples) as the cutoff value to differentiate positive from negative samples. Under this criterion, two horses experimentally infected with WNV were diagnosed as positive at 12 and 14 days, respectively, after infection.

The ubiquitin-proteasome system is essential for the productive entry of Japanese encephalitis virus.

PubMed

Wang, Shaobo; Liu, Haibin; Zu, Xiangyang; Liu, Yang; Chen, Liman; Zhu, Xueqin; Zhang, Leike; Zhou, Zheng; Xiao, Gengfu; Wang, Wei

2016-11-01

The host-virus interaction during the cellular entry of Japanese encephalitis virus (JEV) is poorly characterized. The ubiquitin-proteasome system (UPS), the major intracellular proteolytic pathway, mediates diverse cellular processes, including endocytosis and signal transduction, which may be involved in the entry of virus. Here, we showed that the proteasome inhibitors, MG132 and lactacystin, impaired the productive entry of JEV by effectively interfering with viral intracellular trafficking at the stage between crossing cell membrane and the initial translation of the viral genome after uncoating. Using confocal microscopy, it was demonstrated that a proportion of the internalized virions were misdirected to lysosomes following treatment with MG132, resulting in non-productive entry. In addition, using specific siRNAs targeting ubiquitin, we verified that protein ubiquitination was involved in the entry of JEV. Overall, our study demonstrated the UPS is essential for the productive entry of JEV and might represent a potential antiviral target for JEV infection. Copyright © 2016 Elsevier Inc. All rights reserved.

North American Birds as Potential Amplifying Hosts of Japanese Encephalitis Virus

PubMed Central

Nemeth, Nicole; Bosco-Lauth, Angela; Oesterle, Paul; Kohler, Dennis; Bowen, Richard

2012-01-01

Japanese encephalitis virus (JEV) is an emerging arbovirus, and inter-continental spread is an impending threat. The virus is maintained in a transmission cycle between mosquito vectors and vertebrate hosts, including birds. We detected variation in interspecies responses among North American birds to infection with strains of two different JEV genotypes (I and III). Several native North American passerine species and ring-billed gulls had the highest average peak viremia titers after inoculation with a Vietnamese (genotype I) JEV strain. Oral JEV shedding was minimal and cloacal shedding was rarely detected. The majority of birds, both viremic (72 of 74; 97.3%) and non-viremic (31 of 37; 83.8%), seroconverted by 14 days post-inoculation and West Nile virus-immune individuals had cross-protection against JEV viremia. Reservoir competence and serologic data for a variety of avian taxa are important for development of JEV surveillance and control strategies and will aid in understanding transmission ecology in the event of JEV expansion to North America. PMID:22927494

Japanese Encephalitis in Malaysia: An Overview and Timeline.

PubMed

Kumar, Kiven; Arshad, Siti Suri; Selvarajah, Gayathri Thevi; Abu, Jalila; Toung, Ooi Peck; Abba, Yusuf; Yasmin, A R; Bande, Faruku; Sharma, Reuben; Ong, Bee Lee

2018-05-29

Japanese encephalitis (JE) is a vector-borne zoonotic disease caused by the Japanese encephalitis virus (JEV). It causes encephalitis in human and horses, and may lead to reproductive failure in sows. The first human encephalitis case in Malaya (now Malaysia) was reported during World War II in a British prison in 1942. Later, encephalitis was observed among race horses in Singapore. In 1951, the first JEV was isolated from the brain of an encephalitis patient. The true storyline of JE exposure among humans and animals has not been documented in Malaysia. In some places such as Sarawak, JEV has been isolated from mosquitoes before an outbreak in 1992. JE is an epidemic in Malaysia except Sarawak. There are four major outbreaks reported in Pulau Langkawi (1974), Penang (1988), Perak and Negeri Sembilan (1998-1999), and Sarawak (1992). JE is considered endemic only in Sarawak. Initially, both adults and children were victims of JE in Malaysia, however, according to the current reports; JE infection is only lethal to children in Malaysia. This paper describes a timeline of JE cases (background of each case) from first detection to current status, vaccination programs against JE, diagnostic methods used in hospitals and factors which may contribute to the transmission of JE among humans and animals in Malaysia. Copyright © 2018. Published by Elsevier B.V.

Modulation of neuronal proteome profile in response to Japanese encephalitis virus infection.

PubMed

Sengupta, Nabonita; Ghosh, Sourish; Vasaikar, Suhas V; Gomes, James; Basu, Anirban

2014-01-01

In this study we have reported the in vivo proteomic changes during Japanese Encephalitis Virus (JEV) infection in combination with in vitro studies which will help in the comprehensive characterization of the modifications in the host metabolism in response to JEV infection. We performed a 2-DE based quantitative proteomic study of JEV-infected mouse brain as well as mouse neuroblastoma (Neuro2a) cells to analyze the host response to this lethal virus. 56 host proteins were found to be differentially expressed post JEV infection (defined as exhibiting ≥ 1.5-fold change in protein abundance upon JEV infection). Bioinformatics analyses were used to generate JEV-regulated host response networks which reported that the identified proteins were found to be associated with various cellular processes ranging from intracellular protein transport, cellular metabolism and ER stress associated unfolded protein response. JEV was found to invade the host protein folding machinery to sustain its survival and replication inside the host thereby generating a vigorous unfolded protein response, subsequently triggering a number of pathways responsible for the JEV associated pathologies. The results were also validated using a human cell line to correlate them to the human response to JEV. The present investigation is the first report on JEV-host interactome in in vivo model and will be of potential interest for future antiviral research in this field.

Inhibition of aldolase A blocks biogenesis of ATP and attenuates Japanese encephalitis virus production.

PubMed

Tien, Chih-Feng; Cheng, Shih-Ching; Ho, Yen-Peng; Chen, Yi-Shiuan; Hsu, Jung-Hsin; Chang, Ruey-Yi

2014-01-10

Viral replication depends on host proteins to supply energy and replication accessories for the sufficient production of viral progeny. In this study, we identified fructose-bisphosphate aldolase A as a binding partner of Japanese encephalitis virus (JEV) untranslated regions (UTRs) on the antigenome via RNA affinity capture and mass spectrometry. Direct interaction of aldolase A with JEV RNAs was confirmed by gel mobility shift assay and colocalization with active replication of double-stranded RNA in JEV-infected cells. Infection of JEV caused an increase in aldolase A expression of up to 33%. Knocking down aldolase A reduced viral translation, genome replication, and viral production significantly. Furthermore, JEV infection consumed 50% of cellular ATP, and the ATP level decreased by 70% in the aldolase A-knockdown cells. Overexpression of aldolase A in aldolase A-knockdown cells increased ATP levels significantly. Taken together, these results indicate that JEV replication requires aldolase A and consumes ATP. This is the first report of direct involvement of a host metabolic enzyme, aldolase A protein, in JEV replication. Copyright © 2013 Elsevier Inc. All rights reserved.

Serological evidence of widespread West Nile virus and Japanese encephalitis virus infection in native domestic ducks (Anas platyrhynchos var domesticus) in Kuttanad region, Kerala, India.

PubMed

Kalaiyarasu, Semmannan; Mishra, Niranjan; Khetan, Rohit Kumar; Singh, Vijendra Pal

2016-10-01

Birds can act as reservoirs of West Nile virus (WNV) with a key role in its epidemiology. WNV lineage 1 associated fatal cases of human encephalitis in 2011 and acute flaccid paralysis in 2013 were reported in Alappuzha district, Kerala, India. But no information is available on WNV circulation in domestic ducks, which are abundant, cohabit with humans and occupy wetlands and water bodies in the region. To determine the extent of WNV infection, we investigated 209 sera, 250 oral and 350 cloacal swab samples from local Chara and Chemballi domestic ducks (Anas platyrhynchos var domesticus) in the districts of Alappuzha, Kottayam, Kollam and Pathanamthitta collected during January and March 2015. The serum samples were tested for WNV antibodies first by a competition ELISA and then by a micro virus neutralization test (micro-VNT), while oral and cloacal swabs were subjected to WNV real-time RT-PCR. Ninety five ducks showed evidence of flavivirus antibodies by ELISA. End point neutralizing antibody titre against WNV and Japanese encephalitis virus (JEV) revealed WNV specific antibodies in 24 (11.5%) ducks in 3 districts, JEV specific antibodies in 21 (10%) ducks in 2 districts and flavivirus specific antibodies in 19 (9%) ducks. However, no WNV genomic RNA could be detected. The results of this study demonstrate evidence of widespread WNV and JEV infection in domestic ducks in Kuttanad region, Kerala with a higher seroprevalence to WNV than JEV. Additionally, it highlights the utility of domestic ducks as a surveillance tool to detect WNV/JEV circulation in a region. Copyright © 2016 Elsevier Ltd. All rights reserved.

Persistent West Nile Virus Transmission and the Apparent Displacement St. Louis Encephalitis Virus in Southeastern California, 2003−2006

PubMed Central

REISEN, WILLIAM K.; LOTHROP, HUGH D.; WHEELER, SARAH S.; KENNSINGTON, MARC; GUTIERREZ, ARTURO; FANG, YING; GARCIA, SANDRA; LOTHROP, BRANKA

2008-01-01

West Nile virus (family Flaviviridae, genus Flavivirus, WNV) invaded the Colorado Desert biome of southern California during summer 2003 and seemed to displace previously endemic St. Louis encephalitis virus (family Flaviviridae, genus Flavivirus, SLEV, an antigenically similar Flavivirus in the Japanese encephalitis virus serocomplex). Western equine encephalomyelitis virus (family Togaviridae, genus Alphavirus, WEEV), an antigenically distinct Alphavirus, was detected during 2005 and 2006, indicating that conditions were suitable for encephalitis virus introduction and detection. Cross-protective “avian herd immunity” due to WNV infection possibly may have prevented SLEV reintroduction and/or amplification to detectable levels. During 2003−2006, WNV was consistently active at wetlands and agricultural habitats surrounding the Salton Sea where Culex tarsalis Coquillett served as the primary enzootic maintenance and amplification vector. Based on published laboratory infection studies and the current seroprevalence estimates, house sparrows, house finches, and several Ardeidae may have been important avian amplifying hosts in this region. Transmission efficiency may have been dampened by high infection rates in incompetent avian hosts, including Gamble's quail, mourning doves, common ground doves, and domestic pigeons. Early season WNV amplification and dispersal from North Shore in the southeastern portion of the Coachella Valley resulted in sporadic WNV incursions into the urbanized Upper Valley near Palm Springs, where Culex pipiens quinquefasciatus Say was the primary enzootic and bridge vector. Although relatively few human cases were detected during the 2003−2006 period, all were concentrated in the Upper Valley and were associated with high human population density and WNV infection in peridomestic populations of Cx. p. quinquefasciatus. Intensive early mosquito control during 2006 seemed to interrupt and delay transmission, perhaps setting the stage for the future reintroduction of SLEV. PMID:18533445

Annual Progress Report--Fiscal Year 1979

DTIC Science & Technology

1979-10-01

fever virus Ebola fever virus Korean hemorrhagic fever virus Rift Valley fever virus Bolivian hemorrhagic fever virus...Machupo) Argentinian hemorrhagic fever virus (Junin) Dengue fever virus Congo/Crimean hemorrhagic fever virus Sand fly fever virus Eastern encephalitis...virus Western encephalitis virus Venezuelan fever virus Japanese B fever virus Chikungunya virus Tacaribe virus Pichinde virus Yellow fever

Vectors expressing chimeric Japanese encephalitis dengue 2 viruses.

PubMed

Wei, Y; Wang, S; Wang, X

2014-01-01

Vectors based on self-replicating RNAs (replicons) of flaviviruses are becoming powerful tool for expression of heterologous genes in mammalian cells and development of novel antiviral and anticancer vaccines. We constructed two vectors expressing chimeric viruses consisting of attenuated SA14-14-2 strain of Japanese encephalitis virus (JEV) in which the PrM/M-E genes were replaced fully or partially with those of dengue 2 virus (DENV-2). These vectors, named pJED2 and pJED2-1770 were transfected to BHK-21 cells and produced chimeric viruses JED2V and JED2-1770V, respectively. The chimeric viruses could be passaged in C6/36 but not BHK-21 cells. The chimeric viruses produced in C6/36 cells CPE 4-5 days after infection and RT-PCR, sequencing, immunofluorescence assay (IFA) and Western blot analysis confirmed the chimeric nature of produced viruses. The immunogenicity of chimeric viruses in mice was proved by detecting DENV-2 E protein-specific serum IgG antibodies with neutralization titer of 10. Successful preparation of infectious clones of chimeric JEV-DENV-2 viruses showed that JEV-based expression vectors are fully functional.

Virulence of Japanese Encephalitis Virus Genotypes I and III, Taiwan

PubMed Central

Fan, Yi-Chin; Lin, Jen-Wei; Liao, Shu-Ying; Chen, Jo-Mei; Chen, Yi-Ying; Chiu, Hsien-Chung; Shih, Chen-Chang; Chen, Chi-Ming; Chang, Ruey-Yi; King, Chwan-Chuen; Chen, Wei-June; Ko, Yi-Ting; Chang, Chao-Chin

2017-01-01

The virulence of genotype I (GI) Japanese encephalitis virus (JEV) is under debate. We investigated differences in the virulence of GI and GIII JEV by calculating asymptomatic ratios based on serologic studies during GI- and GIII-JEV endemic periods. The results suggested equal virulence of GI and GIII JEV among humans. PMID:29048288

Yellow fever vector live-virus vaccines: West Nile virus vaccine development.

PubMed

Arroyo, J; Miller, C A; Catalan, J; Monath, T P

2001-08-01

By combining molecular-biological techniques with our increased understanding of the effect of gene sequence modification on viral function, yellow fever 17D, a positive-strand RNA virus vaccine, has been manipulated to induce a protective immune response against viruses of the same family (e.g. Japanese encephalitis and dengue viruses). Triggered by the emergence of West Nile virus infections in the New World afflicting humans, horses and birds, the success of this recombinant technology has prompted the rapid development of a live-virus attenuated candidate vaccine against West Nile virus.

St. Louis encephalitis virus possibly transmitted through blood transfusion-Arizona, 2015.

PubMed

Venkat, Heather; Adams, Laura; Sunenshine, Rebecca; Krow-Lucal, Elisabeth; Levy, Craig; Kafenbaum, Tammy; Sylvester, Tammy; Smith, Kirk; Townsend, John; Dosmann, Melissa; Kamel, Hany; Patron, Roberto; Kuehnert, Matthew; Annambhotla, Pallavi; Basavaraju, Sridhar V; Rabe, Ingrid B

2017-12-01

St. Louis encephalitis virus is a mosquito-borne flavivirus that infrequently causes epidemic central nervous system infections. In the United States, blood donors are not screened for St. Louis encephalitis virus infection, and transmission through blood transfusion has not been reported. During September 2015, St. Louis encephalitis virus infection was confirmed in an Arizona kidney transplant recipient. An investigation was initiated to determine the infection source. The patient was interviewed, and medical records were reviewed. To determine the likelihood of mosquito-borne infection, mosquito surveillance data collected at patient and blood donor residences in timeframes consistent with their possible exposure periods were reviewed. To investigate other routes of exposure, organ and blood donor and recipient specimens were obtained and tested for evidence of St. Louis encephalitis virus infection. The patient presented with symptoms of central nervous system infection. Recent St. Louis encephalitis virus infection was serologically confirmed. The organ donor and three other organ recipients showed no laboratory or clinical evidence of St. Louis encephalitis virus infection. Among four donors of blood products received by the patient via transfusion, one donor had a serologically confirmed, recent St. Louis encephalitis virus infection. Exposure to an infected mosquito was unlikely based on the patient's minimal outdoor exposure. In addition, no St. Louis encephalitis virus-infected mosquito pools were identified around the patient's residence. This investigation provides evidence of the first reported possible case of St. Louis encephalitis virus transmission through blood product transfusion. Health care providers and public health professionals should maintain heightened awareness for St. Louis encephalitis virus transmission through blood transfusion in settings where outbreaks are identified. © 2017 AABB.

Emergence or improved detection of Japanese encephalitis virus in the Himalayan highlands?

PubMed

Baylis, Matthew; Barker, Christopher M; Caminade, Cyril; Joshi, Bhoj R; Pant, Ganesh R; Rayamajhi, Ajit; Reisen, William K; Impoinvil, Daniel E

2016-04-01

The emergence of Japanese encephalitis virus (JEV) in the Himalayan highlands is of significant veterinary and public health concern and may be related to climate warming and anthropogenic landscape change, or simply improved surveillance. To investigate this phenomenon, a One Health approach focusing on the phylogeography of JEV, the distribution and abundance of the mosquito vectors, and seroprevalence in humans and animal reservoirs would be useful to understand the epidemiology of Japanese encephalitis in highland areas. © The Author 2016. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.

miR-370 mimic inhibits replication of Japanese encephalitis virus in glioblastoma cells.

PubMed

Li, Wenjuan; Cheng, Peng; Nie, Shangdan; Cui, Wen

2016-01-01

Japanese encephalitis (JE) is one of the most severe viral infections of the central nervous system. No effective treatment for JE currently exists, because its pathogenesis remains largely unknown. The present study was designed to screen the potential microRNAs (miRNAs) involved in JE. Glioblastoma cells were collected, after being infected with the Japanese encephalitis virus (JEV). Total miRNAs were extracted and analyzed using an miRNA chip. One of the most severely affected miRNAs was selected, and the role of miR-370 in JEV infection was investigated. Cell viability and apoptosis of the host cells were evaluated. JEV replication was detected via analysis of gene E expression. Real-time polymerase chain reaction was used to determine the levels of endogenous miR-370 and expression of innate immunity-related genes. Following JEV infection, 114 miRNAs were affected, as evidenced by the miRNA chip. Among them, 30 miRNAs were upregulated and 84 were downregulated. The changes observed in five miRNAs were confirmed by real-time polymerase chain reaction. One of the significantly downregulated miRNAs was miR-370. Therefore, miR-370 mimic was transfected into the cells, following which the levels of endogenous miR-370 were significantly elevated. Concurrently, JEV replication was significantly reduced 24 hours after transfection of miR-370 mimic. Functionally, miR-370 mimic mitigated both JEV-induced apoptosis and the inhibition of host cell proliferation. Following JEV infection, interferon-β and nuclear factor-kappa B were upregulated, whereas miR-370 mimic prevented the upregulation of the genes induced by JEV infection. The present study demonstrated that miR-370 expression in host cells is downregulated following JEV infection, which further mediates innate immunity-related gene expression. Taken together, miR-370 mimic might be useful to prevent viral replication and infection-induced host cell injury.

Development of Human-Murine Chimeric Immunoglobulin G for Use in the Serological Detection of Human Flavivirus and Alphavirus Antibodies▿

PubMed Central

Thibodeaux, Brett A.; Panella, Amanda N.; Roehrig, John T.

2010-01-01

Diagnosis of human arboviral infections relies heavily on serological techniques such as the immunoglobulin M (IgM) antibody capture enzyme-linked immunosorbent assay (MAC-ELISA) and the indirect IgG ELISA. Broad application of these assays is hindered by the lack of standardized positive human control sera that react with a wide variety of flaviviruses (e.g., dengue, West Nile, yellow fever, Japanese encephalitis, Saint Louis encephalitis, and Powassan viruses), or alphaviruses (e.g., Eastern equine encephalitis, Western equine encephalitis, Venezuelan equine encephalitis, and chikungunya viruses) that can cause human disease. We have created human-murine chimeric monoclonal antibodies (cMAbs) by combining the variable regions of flavivirus (6B6C-1) or alphavirus (1A4B-6) broadly cross-reactive murine MAbs (mMAbs) with the constant region of human IgG1. These cMAbs may be used as standardized reagents capable of replacing human infection-immune-positive control sera in indirect IgG ELISA for diagnosis of all human flaviviral or alphaviral infections. The IgG cMAbs secreted from plasmid-transformed Sp2/0-Ag14 cells had serological activity identical to that of the parent mMAbs, as measured by ELISA using multiple flaviviruses or alphaviruses. PMID:20739503

Development of human-murine chimeric immunoglobulin G for use in the serological detection of human flavivirus and alphavirus antibodies.

PubMed

Thibodeaux, Brett A; Panella, Amanda N; Roehrig, John T

2010-10-01

Diagnosis of human arboviral infections relies heavily on serological techniques such as the immunoglobulin M (IgM) antibody capture enzyme-linked immunosorbent assay (MAC-ELISA) and the indirect IgG ELISA. Broad application of these assays is hindered by the lack of standardized positive human control sera that react with a wide variety of flaviviruses (e.g., dengue, West Nile, yellow fever, Japanese encephalitis, Saint Louis encephalitis, and Powassan viruses), or alphaviruses (e.g., Eastern equine encephalitis, Western equine encephalitis, Venezuelan equine encephalitis, and chikungunya viruses) that can cause human disease. We have created human-murine chimeric monoclonal antibodies (cMAbs) by combining the variable regions of flavivirus (6B6C-1) or alphavirus (1A4B-6) broadly cross-reactive murine MAbs (mMAbs) with the constant region of human IgG1. These cMAbs may be used as standardized reagents capable of replacing human infection-immune-positive control sera in indirect IgG ELISA for diagnosis of all human flaviviral or alphaviral infections. The IgG cMAbs secreted from plasmid-transformed Sp2/0-Ag14 cells had serological activity identical to that of the parent mMAbs, as measured by ELISA using multiple flaviviruses or alphaviruses.

Japanese encephalitis virus non-coding RNA inhibits activation of interferon by blocking nuclear translocation of interferon regulatory factor 3.

PubMed

Chang, Ruey-Yi; Hsu, Ta-Wen; Chen, Yen-Lin; Liu, Shu-Fan; Tsai, Yi-Jer; Lin, Yun-Tong; Chen, Yi-Shiuan; Fan, Yi-Hsin

2013-09-27

Noncoding RNA (ncRNA) plays a critical role in modulating a broad range of diseases. All arthropod-borne flaviviruses produce short fragment ncRNA (sfRNA) collinear with highly conserved regions of the 3'-untranslated region (UTR) in the viral genome. We show that the molar ratio of sfRNA to genomic RNA in Japanese encephalitis virus (JEV) persistently infected cells is greater than that in acutely infected cells, indicating an sfRNA role in establishing persistent infection. Transfecting excess quantities of sfRNA into JEV-infected cells reduced interferon-β (IFN-β) promoter activity by 57% and IFN-β mRNA levels by 52%, compared to mock-transfected cells. Transfection of sfRNA into JEV-infected cells also reduced phosphorylation of interferon regulatory factor-3 (IRF-3), the IFN-β upstream regulator, and blocked roughly 30% of IRF-3 nuclear localization. Furthermore, JEV-infected sfRNA transfected cells produced 23% less IFN-β-stimulated apoptosis than mock-transfected groups did. Taken together, these results suggest that sfRNA plays a role against host-cell antiviral responses, prevents cells from undergoing apoptosis, and thus contributes to viral persistence. Copyright © 2013 Elsevier B.V. All rights reserved.

75 FR 54888 - Determination of Regulatory Review Period for Purposes of Patent Extension; IXIARO

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-09

... marketing the human biologic product IXIARO (Japanese Encephalitis Virus, Vaccine Inactivated, Adsorbed). IXIARO is indicated for active immunization for the prevention of disease caused by Japanese encephalitis...

Challenges of Vaccine Development for Zika Virus.

PubMed

Blackman, Marcia A; Kim, In-Jeong; Lin, Jr-Shiuan; Thomas, Stephen J

2018-03-01

The emergence of outbreaks of Zika virus (ZIKV) in Brazil in 2015 was associated with devastating effects on fetal development and prompted a world health emergency and multiple efforts to generate an effective vaccine against infection. There are now more than 40 vaccine candidates in preclinical development and six in clinical trials. Despite similarities with other flaviviruses to which successful vaccines have been developed, such as yellow fever virus and Japanese Encephalitis virus, there are unique challenges to the development and clinical trials of a vaccine for ZIKV.

Current status of flavivirus vaccines.

PubMed

Barrett, A D

2001-12-01

Although there are approximately 68 flaviviruses recognized, vaccines have been developed to control very few human flavivirus diseases. Licensed live attenuated vaccines have been developed for yellow fever (strain 17D) and Japanese encephalitis (strain SA14-14-2) viruses, and inactivated vaccines have been developed for Japanese encephalitis and tick-borne encephalitis viruses. The yellow fever live attenuated 17D vaccine is one of the most efficacious and safe vaccines developed to date and has been used to immunize more than 300 million people. A number of experimental vaccines are being developed, most notably for dengue. Candidate tetravalent live attenuated dengue vaccines are undergoing clinical trials. Other vaccines are being developed using reverse genetics, DNA vaccines, and recombinant immunogens. In addition, the yellow fever 17D vaccine has been used as a backbone to generate chimeric viruses containing the premembrane and envelope protein genes from other flaviviruses. The "Chimerivax" platform has been used to construct chimeric Japanese encephalitis and dengue viruses that are in different phases of development. Similar strategies are being used by other laboratories.

Molecular Epidemiology of Japanese Encephalitis Virus in Mosquitoes in Taiwan during 2005–2012

PubMed Central

Su, Chien-Ling; Yang, Cheng-Fen; Teng, Hwa-Jen; Lu, Liang-Chen; Lin, Cheo; Tsai, Kun-Hsien; Chen, Yu-Yu; Chen, Li-Yu; Chang, Shu-Fen; Shu, Pei-Yun

2014-01-01

Japanese encephalitis (JE) is a mosquito-borne zoonotic disease caused by the Japanese encephalitis virus (JEV). Pigs and water birds are the main amplifying and maintenance hosts of the virus. In this study, we conducted a JEV survey in mosquitoes captured in pig farms and water bird wetland habitats in Taiwan during 2005 to 2012. A total of 102,633 mosquitoes were collected. Culex tritaeniorhynchus was the most common mosquito species found in the pig farms and wetlands. Among the 26 mosquito species collected, 11 tested positive for JEV by RT-PCR, including Cx. tritaeniorhynchus, Cx. annulus, Anopheles sinensis, Armigeres subalbatus, and Cx. fuscocephala. Among those testing positive, Cx. tritaeniorhynchus was the predominant vector species for the transmission of JEV genotypes I and III in Taiwan. The JEV infection rate was significantly higher in the mosquitoes from the pig farms than those from the wetlands. A phylogenetic analysis of the JEV envelope gene sequences isolated from the captured mosquitoes demonstrated that the predominant JEV genotype has shifted from genotype III to genotype I (GI), providing evidence for transmission cycle maintenance and multiple introductions of the GI strains in Taiwan during 2008 to 2012. This study demonstrates the intense JEV transmission activity in Taiwan, highlights the importance of JE vaccination for controlling the epidemic, and provides valuable information for the assessment of the vaccine's efficacy. PMID:25275652

Immunogenicity of Japanese encephalitis virus envelope protein by Hyphantria cunea nuclear polyhedrosis virus vector in guinea pig.

PubMed

Lee, Hyung-Hoan; Hong, Seung-Kuk; Yoon, Sang-Ho; Jang, Sung-Jae; Bahk, Young-Yil; Song, Min-Dong; Park, Pyo-Jam; Lee, Kwang-Ho; Kim, Chan-Gil; Kim, Bokyung; Park, Tae-Kyu; Kang, Hyun

2012-05-01

Japanese encephalitis virus (JEV) is an important pathogen causing febrile syndrome, encephalitis, and death. Envelop (E) glycoprotein is the major target of inducing neutralizing antibodies and protective immunity in host. In this study, E glycoprotein of JEV was expressed in Spodoptera frugiperd 9 cells as a fusion protein containing a gX signal sequence of pseudorabies virus. This purified HcE recombinant protein was evaluated for their immunogenicity and protective efficacy in guinea pig. The survival rates of guinea pig immunized with HcE protein was significantly increased over that of JE vaccine. This result indicates helpful information for developing a subunit vaccine against JEV.

Neurological Manifestations of Dengue Infection.

PubMed

Li, Guo-Hong; Ning, Zhi-Jie; Liu, Yi-Ming; Li, Xiao-Hong

2017-01-01

Dengue counts among the most commonly encountered arboviral diseases, representing the fastest spreading tropical illness in the world. It is prevalent in 128 countries, and each year >2.5 billion people are at risk of dengue virus infection worldwide. Neurological signs of dengue infection are increasingly reported. In this review, the main neurological complications of dengue virus infection, such as central nervous system (CNS), peripheral nervous system, and ophthalmic complications were discussed according to clinical features, treatment and possible pathogenesis. In addition, neurological complications in children were assessed due to their atypical clinical features. Finally, dengue infection and Japanese encephalitis were compared for pathogenesis and main clinical manifestations.

Molecular evidence for the occurrence of Japanese encephalitis virus genotype I and III infection associated with acute Encephalitis in Patients of West Bengal, India, 2010

PubMed Central

2012-01-01

Background Japanese encephalitis virus (JEV), a mosquito-borne zoonotic pathogen, is the sole etiologic agent of Japanese Encephalitis (JE); a neurotropic killer disease which is one of the major causes of viral encephalitis worldwide with prime public health concern. JE was first reported in the state of West Bengal, India in 1973. Since then it is being reported every year from different districts of the state, though the vaccination has already been done. Therefore, it indicates that there might be either partial coverage of the vaccine or the emergence of mutated/new strain of JEV. Considering this fact, to understand the JEV genotype distribution, we conducted a molecular epidemiological study on a total of 135 serum/cerebrospinal fluid (CSF) samples referred and/or collected from the clinically suspected patients with Acute encephalitis syndrome (AES), admitted in different district hospitals of West Bengal, India, 2010. Findings JEV etiology was confirmed in 36/135 (26.6%) and 13/61 (21.3%) 2–15 days’ febrile illness samples from AES cases by analyzing Mac-ELISA followed by RT-PCR test respectively. Phylogenetic analysis based on complete envelope gene sequences of 13 isolates showed the emergence of JEV genotype I (GI), co-circulating with genotype III (GIII). Conclusion This study represents the first report of JEV GI with GIII, co-circulating in West Bengal. The efficacy of the vaccine (derived from JEV GIII strain SA-14-14-2) to protect against emerging JEV GI needs careful evaluation. In future, JE outbreak is quite likely in the state, if this vaccine fails to protect sufficiently against GI of JEV. PMID:23153306

Brain microvascular endothelial-astrocyte cell responses following Japanese encephalitis virus infection in an in vitro human blood-brain barrier model.

PubMed

Patabendige, Adjanie; Michael, Benedict D; Craig, Alister G; Solomon, Tom

2018-06-01

Japanese encephalitis virus (JEV) remains a leading cause of encephalitis, globally, which continues to grow in importance despite the availability of vaccines. Viral entry into the brain can occur via the blood-brain barrier (BBB), and inflammation at the BBB is a common final pathway in many brain infections. However, the role of the BBB during JEV infection and the contribution of the endothelial and astrocytic cell inflammation in facilitating virus entry into the brain are incompletely understood. We established a BBB model using human brain endothelial cells (HBECs) and human astrocytes. HBECs are polarised, and therefore the model was inoculated by JEV from the apical side to simulate the in vivo situation. The effects of JEV on the BBB permeability and release of inflammatory mediators from both apical and basolateral sides, representing the blood and the brain side respectively were investigated. JEV infected HBECs with limited active virus production, before crossing the BBB and infecting astrocytes. Control of JEV production by HBECs was associated with a significant increase in permeability, and with elevation of many host mediators, including cytokines, chemokines, cellular adhesion molecules, and matrix metalloproteases. When compared to the controls, significantly higher amounts of mediators were released from the apical side as opposed to the basolateral side. The increased release of mediators over time also correlated with increased BBB permeability. Treatment with dexamethasone led to a significant reduction in the release of interleukin 6 (IL6), C-C motif chemokine ligand 5 (CCL5) and C-X-C motif chemokine ligand 10 (CXCL10) from the apical side with a reduction in BBB disruption and no change in JEV production. The results are consistent with the hypothesis that JEV infection of the BBB triggers the production of a range of host mediators from both endothelial cells and astrocytes, which control JEV production but disrupt BBB integrity thus allowing virus entry into the brain. Dexamethasone treatment controlled the host response and limited BBB disruption in the model without increasing JEV production, supporting a re-investigation of its use therapeutically. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

[West Nile virus expanding in Europe].

PubMed

Reusken, Chantal B E M; van Maanen, C Kees; Martina, Byron E; Sonder, Gerard J B; van Gorp, Eric C M; Koopmans, Marion P G

2011-01-01

The areas of Europe in which West Nile virus (WNV)-transmission to humans is observed have expanded over the last few years, with endemic circulation amongst animals of southern Europe. This situation calls for heightened vigilance to the clinical presentation of WNV infection in humans. The average incubation period lasts 2-6 days. Of those infected, 20% will experience a mild, non-specific disease presentation such as high fever, headache, myalgia, possibly with rash and lymphadenopathy; <1% will develop severe neurological symptoms. Rare complications include: myelitis, optic neuritis, rhombencephalitis, polyradiculitis, myocarditis, pancreatitis and fulminant hepatitis. Clinicians should take WNV infection into consideration when making a differential diagnosis for such symptoms in patients who have returned from areas with potential virus circulation. Given the increase in the spread of WNV within Europe, this now holds true for continental travellers as well as those destined for the Americas, Africa and Asia. It is important to include the patient's travel history, clinical symptoms and any occurrences of vaccination against viruses causing Japanese encephalitis, tick-borne encephalitis and yellow fever into the diagnostic workup, as the antibodies against these diseases show cross-reactivity.

Ivermectin is a potent inhibitor of flavivirus replication specifically targeting NS3 helicase activity: new prospects for an old drug.

PubMed

Mastrangelo, Eloise; Pezzullo, Margherita; De Burghgraeve, Tine; Kaptein, Suzanne; Pastorino, Boris; Dallmeier, Kai; de Lamballerie, Xavier; Neyts, Johan; Hanson, Alicia M; Frick, David N; Bolognesi, Martino; Milani, Mario

2012-08-01

Infection with yellow fever virus (YFV), the prototypic mosquito-borne flavivirus, causes severe febrile disease with haemorrhage, multi-organ failure and a high mortality. Moreover, in recent years the Flavivirus genus has gained further attention due to re-emergence and increasing incidence of West Nile, dengue and Japanese encephalitis viruses. Potent and safe antivirals are urgently needed. Starting from the crystal structure of the NS3 helicase from Kunjin virus (an Australian variant of West Nile virus), we identified a novel, unexploited protein site that might be involved in the helicase catalytic cycle and could thus in principle be targeted for enzyme inhibition. In silico docking of a library of small molecules allowed us to identify a few selected compounds with high predicted affinity for the new site. Their activity against helicases from several flaviviruses was confirmed in in vitro helicase/enzymatic assays. The effect on the in vitro replication of flaviviruses was then evaluated. Ivermectin, a broadly used anti-helminthic drug, proved to be a highly potent inhibitor of YFV replication (EC₅₀ values in the sub-nanomolar range). Moreover, ivermectin inhibited, although less efficiently, the replication of several other flaviviruses, i.e. dengue fever, Japanese encephalitis and tick-borne encephalitis viruses. Ivermectin exerts its effect at a timepoint that coincides with the onset of intracellular viral RNA synthesis, as expected for a molecule that specifically targets the viral helicase. The well-tolerated drug ivermectin may hold great potential for treatment of YFV infections. Furthermore, structure-based optimization may result in analogues exerting potent activity against flaviviruses other than YFV.

Ivermectin is a potent inhibitor of flavivirus replication specifically targeting NS3 helicase activity: new prospects for an old drug

PubMed Central

Mastrangelo, Eloise; Pezzullo, Margherita; De Burghgraeve, Tine; Kaptein, Suzanne; Pastorino, Boris; Dallmeier, Kai; de Lamballerie, Xavier; Neyts, Johan; Hanson, Alicia M.; Frick, David N.; Bolognesi, Martino; Milani, Mario

2012-01-01

Objectives Infection with yellow fever virus (YFV), the prototypic mosquito-borne flavivirus, causes severe febrile disease with haemorrhage, multi-organ failure and a high mortality. Moreover, in recent years the Flavivirus genus has gained further attention due to re-emergence and increasing incidence of West Nile, dengue and Japanese encephalitis viruses. Potent and safe antivirals are urgently needed. Methods Starting from the crystal structure of the NS3 helicase from Kunjin virus (an Australian variant of West Nile virus), we identified a novel, unexploited protein site that might be involved in the helicase catalytic cycle and could thus in principle be targeted for enzyme inhibition. In silico docking of a library of small molecules allowed us to identify a few selected compounds with high predicted affinity for the new site. Their activity against helicases from several flaviviruses was confirmed in in vitro helicase/enzymatic assays. The effect on the in vitro replication of flaviviruses was then evaluated. Results Ivermectin, a broadly used anti-helminthic drug, proved to be a highly potent inhibitor of YFV replication (EC50 values in the sub-nanomolar range). Moreover, ivermectin inhibited, although less efficiently, the replication of several other flaviviruses, i.e. dengue fever, Japanese encephalitis and tick-borne encephalitis viruses. Ivermectin exerts its effect at a timepoint that coincides with the onset of intracellular viral RNA synthesis, as expected for a molecule that specifically targets the viral helicase. Conclusions The well-tolerated drug ivermectin may hold great potential for treatment of YFV infections. Furthermore, structure-based optimization may result in analogues exerting potent activity against flaviviruses other than YFV. PMID:22535622

Transcriptional regulation of miR-15b by c-Rel and CREB in Japanese encephalitis virus infection

PubMed Central

Zhu, Bibo; Ye, Jing; Ashraf, Usama; Li, Yunchuan; Chen, Huanchun; Song, Yunfeng; Cao, Shengbo

2016-01-01

MicroRNAs (miRNAs) have been well known to play diverse roles in viral infection at the level of posttranscriptional repression. However, much less is understood about the mechanism by which miRNAs are regulated during viral infection. It is likely that both host and virus contain factors to modulate miRNA expression. Here we report the up-regulation of microRNA-15b (miR-15b) in vitro upon infection with Japanese encephalitis virus (JEV). Analysis of miR-15b precursor, pri-miR-15b and pre-miR-15b, suggest that the regulation occurs transcriptionally. Further, we identified the transcriptional regulatory region of miR-15b that contains consensus binding motif for NF-κB subunit c-Rel and cAMP-response element binding protein (CREB), which are known as transcription factor to regulate gene expression. By promoter fusion and mutational analyses, we demonstrated that c-Rel and CREB bind directly to the promoter elements of miR-15b, which are responsible for miR-15b transcription in response to JEV infection. Finally, we showed that pharmacological inhibition of ERK and NF-κB signaling pathway blocked induction of miR-15b in JEV infection, suggesting important roles of ERK and NF-κB pathway in the regulation of miR-15b gene. Therefore, our observations indicate that induced expression of miR-15b is modulated by c-Rel and CREB in response to JEV infection. PMID:26931521

Structural Study of the C-Terminal Domain of Nonstructural Protein 1 from Japanese Encephalitis Virus.

PubMed

Poonsiri, Thanalai; Wright, Gareth S A; Diamond, Michael S; Turtle, Lance; Solomon, Tom; Antonyuk, Svetlana V

2018-04-01

Japanese encephalitis virus (JEV) is a mosquito-transmitted flavivirus that is closely related to other emerging viral pathogens, including dengue virus (DENV), West Nile virus (WNV), and Zika virus (ZIKV). JEV infection can result in meningitis and encephalitis, which in severe cases cause permanent brain damage and death. JEV occurs predominantly in rural areas throughout Southeast Asia, the Pacific Islands, and the Far East, causing around 68,000 cases of infection worldwide each year. In this report, we present a 2.1-Å-resolution crystal structure of the C-terminal β-ladder domain of JEV nonstructural protein 1 (NS1-C). The surface charge distribution of JEV NS1-C is similar to those of WNV and ZIKV but differs from that of DENV. Analysis of the JEV NS1-C structure, with in silico molecular dynamics simulation and experimental solution small-angle X-ray scattering, indicates extensive loop flexibility on the exterior of the protein. This, together with the surface charge distribution, indicates that flexibility influences the protein-protein interactions that govern pathogenicity. These factors also affect the interaction of NS1 with the 22NS1 monoclonal antibody, which is protective against West Nile virus infection. Liposome and heparin binding assays indicate that only the N-terminal region of NS1 mediates interaction with membranes and that sulfate binding sites common to NS1 structures are not glycosaminoglycan binding interfaces. This report highlights several differences between flavivirus NS1 proteins and contributes to our understanding of their structure-pathogenic function relationships. IMPORTANCE JEV is a major cause of viral encephalitis in Asia. Despite extensive vaccination, epidemics still occur. Nonstructural protein 1 (NS1) plays a role in viral replication, and, because it is secreted, it can exhibit a wide range of interactions with host proteins. NS1 sequence and protein folds are conserved within the Flavivirus genus, but variations in NS1 protein-protein interactions among viruses likely contribute to differences in pathogenesis. Here, we compared characteristics of the C-terminal β-ladder domain of NS1 between flaviviruses, including surface charge, loop flexibility, epitope cross-reactivity, membrane adherence, and glycosaminoglycan binding. These structural features are central to NS1 functionality and may provide insight into the development of diagnostic tests and therapeutics. Copyright © 2018 American Society for Microbiology.

Arboviruses pathogenic for domestic and wild animals.

PubMed

Hubálek, Zdenek; Rudolf, Ivo; Nowotny, Norbert

2014-01-01

The objective of this chapter is to provide an updated and concise systematic review on taxonomy, history, arthropod vectors, vertebrate hosts, animal disease, and geographic distribution of all arboviruses known to date to cause disease in homeotherm (endotherm) vertebrates, except those affecting exclusively man. Fifty arboviruses pathogenic for animals have been documented worldwide, belonging to seven families: Togaviridae (mosquito-borne Eastern, Western, and Venezuelan equine encephalilitis viruses; Sindbis, Middelburg, Getah, and Semliki Forest viruses), Flaviviridae (mosquito-borne yellow fever, Japanese encephalitis, Murray Valley encephalitis, West Nile, Usutu, Israel turkey meningoencephalitis, Tembusu and Wesselsbron viruses; tick-borne encephalitis, louping ill, Omsk hemorrhagic fever, Kyasanur Forest disease, and Tyuleniy viruses), Bunyaviridae (tick-borne Nairobi sheep disease, Soldado, and Bhanja viruses; mosquito-borne Rift Valley fever, La Crosse, Snowshoe hare, and Cache Valley viruses; biting midges-borne Main Drain, Akabane, Aino, Shuni, and Schmallenberg viruses), Reoviridae (biting midges-borne African horse sickness, Kasba, bluetongue, epizootic hemorrhagic disease of deer, Ibaraki, equine encephalosis, Peruvian horse sickness, and Yunnan viruses), Rhabdoviridae (sandfly/mosquito-borne bovine ephemeral fever, vesicular stomatitis-Indiana, vesicular stomatitis-New Jersey, vesicular stomatitis-Alagoas, and Coccal viruses), Orthomyxoviridae (tick-borne Thogoto virus), and Asfarviridae (tick-borne African swine fever virus). They are transmitted to animals by five groups of hematophagous arthropods of the subphyllum Chelicerata (order Acarina, families Ixodidae and Argasidae-ticks) or members of the class Insecta: mosquitoes (family Culicidae); biting midges (family Ceratopogonidae); sandflies (subfamily Phlebotominae); and cimicid bugs (family Cimicidae). Arboviral diseases in endotherm animals may therefore be classified as: tick-borne (louping ill and tick-borne encephalitis, Omsk hemorrhagic fever, Kyasanur Forest disease, Tyuleniy fever, Nairobi sheep disease, Soldado fever, Bhanja fever, Thogoto fever, African swine fever), mosquito-borne (Eastern, Western, and Venezuelan equine encephalomyelitides, Highlands J disease, Getah disease, Semliki Forest disease, yellow fever, Japanese encephalitis, Murray Valley encephalitis, West Nile encephalitis, Usutu disease, Israel turkey meningoencephalitis, Tembusu disease/duck egg-drop syndrome, Wesselsbron disease, La Crosse encephalitis, Snowshoe hare encephalitis, Cache Valley disease, Main Drain disease, Rift Valley fever, Peruvian horse sickness, Yunnan disease), sandfly-borne (vesicular stomatitis-Indiana, New Jersey, and Alagoas, Cocal disease), midge-borne (Akabane disease, Aino disease, Schmallenberg disease, Shuni disease, African horse sickness, Kasba disease, bluetongue, epizootic hemorrhagic disease of deer, Ibaraki disease, equine encephalosis, bovine ephemeral fever, Kotonkan disease), and cimicid-borne (Buggy Creek disease). Animals infected with these arboviruses regularly develop a febrile disease accompanied by various nonspecific symptoms; however, additional severe syndromes may occur: neurological diseases (meningitis, encephalitis, encephalomyelitis); hemorrhagic symptoms; abortions and congenital disorders; or vesicular stomatitis. Certain arboviral diseases cause significant economic losses in domestic animals-for example, Eastern, Western and Venezuelan equine encephalitides, West Nile encephalitis, Nairobi sheep disease, Rift Valley fever, Akabane fever, Schmallenberg disease (emerged recently in Europe), African horse sickness, bluetongue, vesicular stomatitis, and African swine fever; all of these (except for Akabane and Schmallenberg diseases) are notifiable to the World Organisation for Animal Health (OIE, 2012). © 2014 Elsevier Inc. All rights reserved.

Seroprevalence of West Nile Virus in Wild Birds in Far Eastern Russia Using a Focus Reduction Neutralization Test

PubMed Central

Murata, Ryo; Hashiguchi, Kazuaki; Yoshii, Kentaro; Kariwa, Hiroaki; Nakajima, Kensuke; Ivanov, Leonid I.; Leonova, Galina N.; Takashima, Ikuo

2011-01-01

West Nile (WN) virus has been spreading geographically to non-endemic areas in various parts of the world. However, little is known about the extent of WN virus infection in Russia. Japanese encephalitis (JE) virus, which is closely related to WN virus, is prevalent throughout East Asia. We evaluated the effectiveness of a focus reduction neutralization test in young chicks inoculated with JE and WN viruses, and conducted a survey of WN infection among wild birds in Far Eastern Russia. Following single virus infection, only neutralizing antibodies specific to the homologous virus were detected in chicks. The neutralization test was then applied to serum samples from 145 wild birds for WN and JE virus. Twenty-one samples were positive for neutralizing antibodies to WN. These results suggest that WN virus is prevalent among wild birds in the Far Eastern region of Russia. PMID:21363987

Gold nanoparticle-based RT-PCR and real-time quantitative RT-PCR assays for detection of Japanese encephalitis virus

NASA Astrophysics Data System (ADS)

Huang, Su-Hua; Yang, Tsuey-Ching; Tsai, Ming-Hong; Tsai, I.-Shou; Lu, Huang-Chih; Chuang, Pei-Hsin; Wan, Lei; Lin, Ying-Ju; Lai, Chih-Ho; Lin, Cheng-Wen

2008-10-01

Virus isolation and antibody detection are routinely used for diagnosis of Japanese encephalitis virus (JEV) infection, but the low level of transient viremia in some JE patients makes JEV isolation from clinical and surveillance samples very difficult. We describe the use of gold nanoparticle-based RT-PCR and real-time quantitative RT-PCR assays for detection of JEV from its RNA genome. We tested the effect of gold nanoparticles on four different PCR systems, including conventional PCR, reverse-transcription PCR (RT-PCR), and SYBR green real-time PCR and RT-PCR assays for diagnosis in the acute phase of JEV infection. Gold nanoparticles increased the amplification yield of the PCR product and shortened the PCR time compared to the conventional reaction. In addition, nanogold-based real-time RT-PCR showed a linear relationship between Ct and template amount using ten-fold dilutions of JEV. The nanogold-based RT-PCR and real-time quantitative RT-PCR assays were able to detect low levels (1-10 000 copies) of the JEV RNA genomes extracted from culture medium or whole blood, providing early diagnostic tools for the detection of low-level viremia in the acute-phase infection. The assays described here were simple, sensitive, and rapid approaches for detection and quantitation of JEV in tissue cultured samples as well as clinical samples.

Detection of Japanese Encephalitis Virus RNA in Human Throat Samples in Laos - A Pilot study.

PubMed

Bharucha, Tehmina; Sengvilaipaseuth, Onanong; Seephonelee, Malee; Vongsouvath, Malavanh; Vongsouvath, Manivanh; Rattanavong, Sayaphet; Piorkowski, Géraldine; Lecuit, Marc; Gorman, Christopher; Pommier, Jean-David; Newton, Paul N; de Lamballerie, Xavier; Dubot-Pérès, Audrey

2018-05-22

Japanese encephalitis virus (JEV) is the most commonly identified cause of acute encephalitis syndrome (AES) in Asia. The WHO recommended test is anti-JEV IgM-antibody-capture-enzyme-linked-immunosorbent-assay (JEV MAC-ELISA). However, data suggest this has low positive predictive value, with false positives related to other Flavivirus infections and vaccination. JEV RT-PCR in cerebrospinal fluid (CSF) and/or serum is highly specific, but is rarely positive; 0-25% of patients that fulfil the WHO definition of JE (clinical Acute Encephalitis Syndrome (AES) and JEV MAC-ELISA positive). Testing other body fluids by JEV RT-qPCR may improve the diagnosis. As a pilot study thirty patients admitted to Mahosot Hospital 2014-2017, recruited to the South-East-Asia-Encephalitis study, were tested by JEV MAC-ELISA and two JEV real-time RT-PCR (RT-qPCR) assays (NS2A and NS3). Eleven (36.7%) were JEV MAC-ELISA positive. Available CSF and serum samples of these patients were JEV RT-qPCR negative but 2 (7%) had JEV RNA detected in their throat swabs. JEV RNA was confirmed by re-testing, and sequencing of RT-qPCR products. As the first apparent report of JEV RNA detection in human throat samples, the provides new perspectives on human JEV infection, potentially informing improving JEV detection. We suggest that testing patients' throat swabs for JEV RNA is performed, in combination with molecular and serological CSF and serum investigations, on a larger scale to investigate the epidemiology of the presence of JEV in human throats. Throat swabs are an easy and non-invasive tool that could be rolled out to a wider population to improve knowledge of JEV molecular epidemiology.

New developments in flavivirus vaccines with special attention to yellow fever.

PubMed

Pugachev, Konstantin V; Guirakhoo, Farshad; Monath, Thomas P

2005-10-01

Here we review recent epidemiological trends in flavivirus diseases, findings related to existing vaccines, and new directions in flavivirus vaccine research. We emphasize the need for stepped-up efforts to stop further spread and intensification of these infections worldwide. Although the incidence and geographic distribution of flavivirus diseases have increased in recent years, human vaccines are available only for yellow fever, Japanese encephalitis, tick-borne encephalitis and Kyasanur forest disease. Factors contributing to resurgence include insufficient supplies of available vaccines, incomplete vaccination coverage and relaxation in vector control. Research has been underway for 60 years to develop effective vaccines against dengue, and recent progress is encouraging. The development of vaccines against West Nile, virus recently introduced to North America, has been initiated. In addition, there is considerable interest in improving existing vaccines with respect to increasing safety (e.g. eliminating the newly recognized syndrome of yellow fever vaccine-associated viscerotropic adverse disease), and to reducing the cost and number of doses required for effective immunization. Traditional approaches to flavivirus vaccines are still employed, while recent advancements in biotechnology produced new approaches to vaccine design, such as recombinant live virus, subunit and DNA vaccines. Live chimeric vaccines against dengue, Japanese encephalitis and West Nile based on yellow fever 17D virus (ChimeriVax) are in phase I/II trials, with encouraging results. Other chimeric dengue, tick-borne encephalitis and West Nile virus candidates were developed based on attenuated dengue backbones. To further reduce the impact of flavivirus diseases, vaccination policies and vector control programs in affected countries require revision.

Antiviral macrophage responses in flavivirus encephalitis

PubMed Central

Ashhurst, Thomas Myles; van Vreden, Caryn; Munoz-Erazo, Luis; Niewold, Paula; Watabe, Kanami; Terry, Rachael L.; Deffrasnes, Celine; Getts, Daniel R.; King, Nicholas Jonathan Cole

2013-01-01

Mosquito-borne flaviviruses are a major current and emerging threat, affecting millions of people worldwide. Global climate change, combined with increasing proximity of humans to animals and mosquito vectors by expansion into natural habitats, coupled with the increase in international travel, have resulted in significant spread and concomitant increase in the incidence of infection and severe disease. Although neuroinvasive disease has been well described for some viral infections such as Japanese Encephalitis virus (JEV) and West Nile virus (WNV), others such as dengue virus (DENV) have recently displayed an emerging pattern of neuroinvasive disease, distinct from the previously observed, systemically-induced encephalomyelopathy. In this setting, the immune response is a crucial component of host defence, in preventing viral dissemination and invasion of the central nervous system (CNS). However, subversion of the anti-viral activities of macrophages by flaviviruses can facilitate viral replication and spread, enhancing the intensity of immune responses, leading to severe immune-mediated disease which may be further exacerbated during the subsequent infection with some flaviviruses. Furthermore, in the CNS myeloid cells may be responsible for inducing specific inflammatory changes, which can lead to significant pathological damage during encephalitis. The interaction of virus and cells of the myeloid lineage is complex, and this interaction is likely responsible at least in part, for crucial differences between viral clearance and pathology. Recent studies on the role of myeloid cells in innate immunity and viral control, and the mechanisms of evasion and subversion used by flaviviruses are rapidly advancing our understanding of the immunopathological mechanisms involved in flavivirus encephalitis and will lead to the development of therapeutic strategies previously not considered. PMID:24434318

Pigsties near dwellings as a potential risk factor for the prevalence of Japanese encephalitis virus in adult in Shanxi, China.

PubMed

Ren, Xiaojie; Fu, Shihong; Dai, Peifang; Wang, Huanyu; Li, Yuanyuan; Li, Xiaolong; Lei, Wenwen; Gao, Xiaoyan; He, Ying; Lv, Zhi; Cheng, Jingxia; Wang, Guiqin; Liang, Guodong

2017-06-08

The increasing trend of adult cases of Japanese encephalitis (JE) in China, particularly in northern China, has become an important public health issue. We conducted an epidemiological investigation in the south of Shanxi Province to examine the relationships between mosquitoes, Japanese encephalitis virus (JEV), and adult JE cases. Mosquito specimens were collected from the courtyards of farmers' households and pig farms in Shanxi Province. Mosquitoes were pooled, homogenized, and centrifuged. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect mosquito-borne arbovirus genes in homogenates. Specimens positive for these genes were inoculated into the baby hamster kidney cell line (BHK-21) to isolate virus. Minimum infection rate was calculated and phylogenetic analyses were performed. A total of 7 943 mosquitoes belonging to six species in four genera were collected; Culex tritaeniorhynchus accounted for 73.08% (5 805/7 943), C. pipiens pallens for 24.75% (1 966/7 943), and the remaining 3% (104/ 7943) consisted of Anopheles sinensis, Aedes vexans, Ae. dorsalis, and Armigeres subalbatus. Sixteen pools were positive for JEV based on RT-PCR using JEV pre-membrane gene nested primers. Phylogenetic analyses showed that all JEVs belonged to genotype I; two pools were positive using Getah Virus (GETV) gene primers. In addition, one JEV strain (SXYC1523) was isolated from C. pipiens pallens specimens. These results indicate that the minimum infection rate of JEV in mosquito specimens collected from the courtyards of farmers' households with pigsties was 7.39/1 000; the rate for pig farms was 2.68/1 000; and the rate for farmers' courtyards without pigsties was zero. The high-prevalence regions of adult JE investigated in this study are still the natural epidemic focus of JEV. Having pigsties near dwellings is a potential risk factor contributing to the prevalence of adult JE. To prevent the occurrence of local adult JE cases, a recommendation was raised that, besides continuing to implement the Expanded Program on Immunization for children, the government should urge local farmers to cease raising pigs in their own courtyards to reduce the probability of infection with JEV.

Regulation of Apoptosis during Flavivirus Infection.

PubMed

Okamoto, Toru; Suzuki, Tatsuya; Kusakabe, Shinji; Tokunaga, Makoto; Hirano, Junki; Miyata, Yuka; Matsuura, Yoshiharu

2017-08-28

Apoptosis is a type of programmed cell death that regulates cellular homeostasis by removing damaged or unnecessary cells. Its importance in host defenses is highlighted by the observation that many viruses evade, obstruct, or subvert apoptosis, thereby blunting the host immune response. Infection with Flaviviruses such as Japanese encephalitis virus (JEV), Dengue virus (DENV) and West Nile virus (WNV) has been shown to activate several signaling pathways such as endoplasmic reticulum (ER)-stress and AKT/PI3K pathway, resulting in activation or suppression of apoptosis in virus-infected cells. On the other hands, expression of some viral proteins induces or protects apoptosis. There is a discrepancy between induction and suppression of apoptosis during flavivirus infection because the experimental situation may be different, and strong links between apoptosis and other types of cell death such as necrosis may make it more difficult. In this paper, we review the effects of apoptosis on viral propagation and pathogenesis during infection with flaviviruses.

Genotype I of Japanese Encephalitis Virus Virus-like Particles Elicit Sterilizing Immunity against Genotype I and III Viral Challenge in Swine.

PubMed

Fan, Yi-Chin; Chen, Jo-Mei; Lin, Jen-Wei; Chen, Yi-Ying; Wu, Guan-Hong; Su, Kuan-Hsuan; Chiou, Ming-Tang; Wu, Shang-Rung; Yin, Ji-Hang; Liao, Jiunn-Wang; Chang, Gwong-Jen J; Chiou, Shyan-Song

2018-05-10

Swine are a critical amplifying host involved in human Japanese encephalitis (JE) outbreaks. Cross-genotypic immunogenicity and sterile protection are important for the current genotype III (GIII) virus-derived vaccines in swine, especially now that emerging genotype I (GI) JE virus (JEV) has replaced GIII virus as the dominant strain. Herein, we aimed to develop a system to generate GI JEV virus-like particles (VLPs) and evaluate the immunogenicity and protection of the GI vaccine candidate in mice and specific pathogen-free swine. A CHO-heparan sulfate-deficient (CHO-HS(-)) cell clone, named 51-10 clone, stably expressing GI-JEV VLP was selected and continually secreted GI VLPs without signs of cell fusion. 51-10 VLPs formed a homogeneously empty-particle morphology and exhibited similar antigenic activity as GI virus. GI VLP-immunized mice showed balanced cross-neutralizing antibody titers against GI to GIV viruses (50% focus-reduction micro-neutralization assay titers 71 to 240) as well as potent protection against GI or GIII virus infection. GI VLP-immunized swine challenged with GI or GIII viruses showed no fever, viremia, or viral RNA in tonsils, lymph nodes, and brains as compared with phosphate buffered saline-immunized swine. We thus conclude GI VLPs can provide sterile protection against GI and GIII viruses in swine.

Role of host cell factors in flavivirus infection: Implications for pathogenesis and development of antiviral drugs.

PubMed

Pastorino, Boris; Nougairède, Antoine; Wurtz, Nathalie; Gould, Ernest; de Lamballerie, Xavier

2010-09-01

The genus Flavivirus contains approximately 70 arthropod-borne enveloped RNA viruses many of which cause severe human and in some cases, animal disease. They include dengue virus, yellow fever virus, West Nile virus, Japanese encephalitis virus, and tick-borne encephalitis virus. Hundreds of thousands of deaths due to flavivirus infections occur each year, many of which are unpreventable due to lack of availability of appropriate vaccines and/or antiviral drugs. Flaviviruses exploit the cytoplasmic cellular machinery to facilitate propagation of infectious progeny virions. They engage in dynamic and antagonistic interactions with host cell membranes and biochemical processes. Following infection, the cells initiate various antiviral strategies to counteract viral invasion. In its defense, the virus has alternative strategies to suppress these host responses to infection. The fine balance between these interactions determines the outcome of the viral infection and disease progression. Published studies have revealed specific effects of flaviviruses on cellular processes, but the underlying mechanisms that determine the specific cytopathogenetic changes induced by different flaviviruses have not, as yet, been elucidated. Independently of the suppression of the type I IFN response which has been described in detail elsewhere, this review focuses on recent discoveries relating to alterations of host metabolism following viral infection. Such studies may contribute to new approaches to antiviral drug development. The role of host cellular factors will be examined in the context of protection and/or pathogenesis resulting from flavivirus infection, with particular emphasis on West Nile virus and dengue virus. 2010 Elsevier B.V. All rights reserved.

Dynamic changes in global microRNAome and transcriptome reveal complex miRNA-mRNA regulated host response to Japanese Encephalitis Virus in microglial cells

PubMed Central

Kumari, Bharti; Jain, Pratistha; Das, Shaoli; Ghosal, Suman; Hazra, Bibhabasu; Trivedi, Ashish Chandra; Basu, Anirban; Chakrabarti, Jayprokas; Vrati, Sudhanshu; Banerjee, Arup

2016-01-01

Microglia cells in the brain play essential role during Japanese Encephalitis Virus (JEV) infection and may lead to change in microRNA (miRNA) and mRNA profile. These changes may together control disease outcome. Using Affymetrix microarray platform, we profiled cellular miRNA and mRNA expression at multiple time points during viral infection in human microglial (CHME3) cells. In silico analysis of microarray data revealed a phased pattern of miRNAs expression, associated with JEV replication and provided unique signatures of infection. Target prediction and pathway enrichment analysis identified anti correlation between differentially expressed miRNA and the gene expression at multiple time point which ultimately affected diverse signaling pathways including Notch signaling pathways in microglia. Activation of Notch pathway during JEV infection was demonstrated in vitro and in vivo. The expression of a subset of miRNAs that target multiple genes in Notch signaling pathways were suppressed and their overexpression could affect JEV induced immune response. Further analysis provided evidence for the possible presence of cellular competing endogenous RNA (ceRNA) associated with innate immune response. Collectively, our data provide a uniquely comprehensive view of the changes in the host miRNAs induced by JEV during cellular infection and identify Notch pathway in modulating microglia mediated inflammation. PMID:26838068

Dynamic changes in global microRNAome and transcriptome reveal complex miRNA-mRNA regulated host response to Japanese Encephalitis Virus in microglial cells.

PubMed

Kumari, Bharti; Jain, Pratistha; Das, Shaoli; Ghosal, Suman; Hazra, Bibhabasu; Trivedi, Ashish Chandra; Basu, Anirban; Chakrabarti, Jayprokas; Vrati, Sudhanshu; Banerjee, Arup

2016-02-03

Microglia cells in the brain play essential role during Japanese Encephalitis Virus (JEV) infection and may lead to change in microRNA (miRNA) and mRNA profile. These changes may together control disease outcome. Using Affymetrix microarray platform, we profiled cellular miRNA and mRNA expression at multiple time points during viral infection in human microglial (CHME3) cells. In silico analysis of microarray data revealed a phased pattern of miRNAs expression, associated with JEV replication and provided unique signatures of infection. Target prediction and pathway enrichment analysis identified anti correlation between differentially expressed miRNA and the gene expression at multiple time point which ultimately affected diverse signaling pathways including Notch signaling pathways in microglia. Activation of Notch pathway during JEV infection was demonstrated in vitro and in vivo. The expression of a subset of miRNAs that target multiple genes in Notch signaling pathways were suppressed and their overexpression could affect JEV induced immune response. Further analysis provided evidence for the possible presence of cellular competing endogenous RNA (ceRNA) associated with innate immune response. Collectively, our data provide a uniquely comprehensive view of the changes in the host miRNAs induced by JEV during cellular infection and identify Notch pathway in modulating microglia mediated inflammation.

miR-146a negatively regulates the induction of proinflammatory cytokines in response to Japanese encephalitis virus infection in microglial cells.

PubMed

Deng, Minnan; Du, Ganqin; Zhao, Jiegang; Du, Xiaowei

2017-06-01

Increasing evidence confirms the involvement of virus infection and miRNA, such as miR-146a, in neuroinflammation-associated epilepsy. In the present study, we investigated the upregulation of miR-146a with RT-qPCR and in situ hybridization methods in a mice infection model of Japanese encephalitis virus (JEV) and in vitro. Subsequently we investigated the involvement of miR-146a in modulating JEV-induced neuroinflammation. It was demonstrated that JEV infection promoted miR-146a production in BALB/c mice brain and in cultured mouse microglial C8-B4 cells, along with pro-inflammatory cytokines, such as IL-1β, IL-6, TNF-α, IFN-β and IFN-α. We also found that miR-146a exerted negative regulatory effects upon IL-1β, IL-6, TNF-α, IFN-β and IFN-α in C8-B4 cells. Accordingly, miR-146a downregulation with a miR-146a inhibitor promoted the upregulation of IL-1β, IL-6, TNF-α, IFN-β and IFN-α, whereas miR-146a upregulation with miR-146a mimics reduced the upregulation of these cytokines. Moreover, miR-146a exerted no regulation upon JEV growth in C8-B4 cells. In conclusion, JEV infection upregulated miR-146a and pro-inflammatory cytokine production, in mice brain and in cultured C8-B4 cells. Furthermore, miR-146a negatively regulated the production of JEV-induced pro-inflammatory cytokines, in virus growth independent fashion, identifying miR-146a as a negative feedback regulator in JEV-induced neuroinflammation, and possibly in epilepsy.

Infectious Causes and Infectious Mimics of Acute Encephalitis: a Prospective Study from Thailand

PubMed Central

Skulsujirapa, Benjawan; Wacharapluesadee, Supaporn; Petcharat, Sininat; Hemachudha, Thiravat; Wasontiwong, Abhinbhen Saraya; Putcharoen, Opass

2017-01-01

Abstract Background Previous reports of infectious encephalitis in Thailand showed viruses as major pathogens similar to worldwide data. Major viruses in studies varied among Japanese encephalitis, Enteroviruses and Herpesviruses. Infectious etiologies vary by regions, seasons and preventive strategies done. Dynamic change of pathogen is believed to occur continually. Local data in each region is important to develop an algorithm of investigations for the cost-effectiveness. Methods This is a prospective study of patients with encephalitis between January 2014 to March 2017 at a tertiary hospital in Bangkok. Microbiological and serological studies were done according to an algorithm based on initial cerebrospinal fluid analysis. Initial tests were for bacteria, fungus, mycobacterium and commonly prevalent viruses. Further tests for infectious etiology were done by stepwise approach if initial tests yielded negative. Results Fifty-two patients were enrolled. Twenty-seven (51.9%) patients had no etiology identified. Three patients (5.8%) had bacterial etiology, 10 (19.2%) had viral etiology, and 12 (23%) had immune-mediated encephalitis. Among viral etiologies, VZV was identified in 4 cases, HSV in 3 cases, CMV in 2 cases and measles in 1 case. Baseline characteristic of HIV infection or skin rash was associated with viral infection (p 0.031, p 0.006). Patients with VZV encephalitis might not have active skin lesion. The presence of prodrome, duration of prodrome, neurological onset to peak and physical examination of focal neurodeficit, meningeal irritation signs, and reflex were similar across all etiologies. White blood cell [mean 7.0 (range 0–30) cells/µL] and protein [mean 32.5 (range 11–70.4) mg/dL] from the cerebrospinal fluid of noninfectious etiologies tended to be lower than the levels of infectious causes (p 0.009, p 0.020). All patients survived at 7 days after admission. Conclusion A quarter of patients presenting with acute encephalitis in this study had autoimmune and paraneoplastic encephalitis. Infections caused by herpesviruses was the most prevalent viral etiology. Autoimmune and paraneoplastic encephalitis should be kept in the differential diagnosis in patients with acute encephalitis. Disclosures S. Wacharapluesadee, USAID: Investigator, Research grant. O. Putcharoen, USAID: Grant Investigator, Research grant.

Cross-protection between West Nile and Japanese encephalitis viruses in red-winged blackbirds (Agelaius phoeniceus).

PubMed

Nemeth, Nicole M; Bosco-Lauth, Angela M; Bowen, Richard A

2009-09-01

Similar to West Nile virus (WNV), Japanese encephalitis virus (JEV) has a history of intercontinental spread, and birds are important for the maintenance and transmission of both of these closely related viruses. We examined viremic and serologic responses of blackbirds (Agelaius phoeniceus), with and without immunity to WNV, following experimental inoculation with two strains of JEV. Japanese encephalitis (JE) viremia was detected in only one of 16 (6.3%) WNV-immune birds, while all 16 nonimmune birds had detectable JE viremia. Two weeks after JEV inoculation, all birds without pre-existing WNV immunity had clearly distinguishable anti-JEV antibodies, while in all birds with pre-existing WNV immunity, antibodies to WNV and JEV were either indistinguishable or the anti-WNV antibody titers were significantly higher. As WNV is endemic throughout much of North America, WNV immunity among birds may dampen transmission while complicating the serologic diagnosis of JEV, should this pathogen be introduced to North America.

A Serological Protein Microarray for Detection of Multiple Cross-Reactive Flavivirus Infections in Horses for Veterinary and Public Health Surveillance.

PubMed

Cleton, N B; van Maanen, K; Bergervoet, S A; Bon, N; Beck, C; Godeke, G-J; Lecollinet, S; Bowen, R; Lelli, D; Nowotny, N; Koopmans, M P G; Reusken, C B E M

2017-12-01

The genus Flavivirus in the family Flaviviridae includes some of the most important examples of emerging zoonotic arboviruses that are rapidly spreading across the globe. Japanese encephalitis virus (JEV), West Nile virus (WNV), St. Louis encephalitis virus (SLEV) and Usutu virus (USUV) are mosquito-borne members of the JEV serological group. Although most infections in humans are asymptomatic or present with mild flu-like symptoms, clinical manifestations of JEV, WNV, SLEV, USUV and tick-borne encephalitis virus (TBEV) can include severe neurological disease and death. In horses, infection with WNV and JEV can lead to severe neurological disease and death, while USUV, SLEV and TBEV infections are mainly asymptomatic, however, and induce antibody responses. Horses often serve as sentinels to monitor active virus circulation in serological surveillance programmes specifically for WNV, USUV and JEV. Here, we developed and validated a NS1-antigen protein microarray for the serological differential diagnosis of flavivirus infections in horses using sera of experimentally and naturally infected symptomatic as well as asymptomatic horses. Using samples from experimentally infected horses, an IgG and IgM specificity of 100% and a sensitivity of 95% for WNV and 100% for JEV was achieved with a cut-off titre of 1 : 20 based on ROC calculation. In field settings, the microarray identified 93-100% of IgG-positive horses with recent WNV infections and 87% of TBEV IgG-positive horses. WNV IgM sensitivity was 80%. Differentiation between closely related flaviviruses by the NS1-antigen protein microarray is possible, even though we identified some instances of cross-reactivity among antibodies. However, the assay is not able to differentiate between naturally infected horses and animals vaccinated with an inactivated WNV whole-virus vaccine. We showed that the NS1-microarray can potentially be used for diagnosing and distinguishing flavivirus infections in horses and for public health purposes within a surveillance setting. This allows for fast, cheap, syndrome-based laboratory testing for multiple viruses simultaneously for veterinary and public health purposes. © 2016 Blackwell Verlag GmbH.

A Single Amino Acid Substitution in the NS2A Protein of Japanese Encephalitis Virus Affects Virus Propagation In Vitro but Not In Vivo.

PubMed

Takamatsu, Yuki; Morita, Kouichi; Hayasaka, Daisuke

2015-06-01

We identified a unique amino acid of NS2A113, phenylalanine, that affects the efficient propagation of two Japanese encephalitis virus strains, JaTH160 and JaOArS982, in neuroblastoma Neuro-2a cells but not in cell lines of extraneural origin. This amino acid did not affect viral loads in the brain or survival curves in mice. These findings suggest that virus propagation in vitro may not reflect the level of virus neuroinvasiveness in vivo. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Protein Interactions during the Flavivirus and Hepacivirus Life Cycle*

PubMed Central

Bruening, Janina; Weigel, Bettina; Pietschmann, Thomas

2017-01-01

Protein–protein interactions govern biological functions in cells, in the extracellular milieu, and at the border between cells and extracellular space. Viruses are small intracellular parasites and thus rely on protein interactions to produce progeny inside host cells and to spread from cell to cell. Usage of host proteins by viruses can have severe consequences e.g. apoptosis, metabolic disequilibria, or altered cell proliferation and mobility. Understanding protein interactions during virus infection can thus educate us on viral infection and pathogenesis mechanisms. Moreover, it has led to important clinical translations, including the development of new therapeutic and vaccination strategies. Here, we will discuss protein interactions of members of the Flaviviridae family, which are small enveloped RNA viruses. Dengue virus, Zika virus and hepatitis C virus belong to the most prominent human pathogenic Flaviviridae. With a genome of roughly ten kilobases encoding only ten viral proteins, Flaviviridae display intricate mechanisms to engage the host cell machinery for their purpose. In this review, we will highlight how dengue virus, hepatitis C virus, Japanese encephalitis virus, tick-borne encephalitis virus, West Nile virus, yellow fever virus, and Zika virus proteins engage host proteins and how this knowledge helps elucidate Flaviviridae infection. We will specifically address the protein composition of the virus particle as well as the protein interactions during virus entry, replication, particle assembly, and release from the host cell. Finally, we will give a perspective on future challenges in Flaviviridae interaction proteomics and why we believe these challenges should be met. PMID:28077444

The Antigenic Structure of Zika Virus and Its Relation to Other Flaviviruses: Implications for Infection and Immunoprophylaxis.

PubMed

Heinz, Franz X; Stiasny, Karin

2017-03-01

Zika virus was discovered ∼70 years ago in Uganda and maintained a low profile as a human disease agent in Africa and Asia. Only recently has it caused explosive outbreaks in previously unaffected regions, first in Oceania and then in the Americas since 2015. Of special concern is the newly identified link between congenital malformations (especially microcephaly) and Zika virus infections during pregnancy. At present, it is unclear whether Zika virus changed its pathogenicity or whether the huge number of infections allowed the recognition of a previously cryptic pathogenic property. The purpose of this review is to discuss recent data on the molecular antigenic structure of Zika virus in the context of antibody-mediated neutralization and antibody-dependent enhancement (ADE) of infection, a phenomenon that has been implicated in the development of severe disease caused by the related dengue viruses. Emphasis is given to epitopes of antibodies that potently neutralize Zika virus and also to epitopes that provide antigenic links to other important human-pathogenic flaviviruses such as dengue, yellow fever, West Nile, Japanese encephalitis, and tick-borne encephalitis viruses. The antigenic cross talk between Zika and dengue viruses appears to be of special importance, since they cocirculate in many regions of endemicity and sequential infections are likely to occur frequently. New insights into the molecular antigenic structure of Zika virus and flaviviruses in general have provided the foundation for great progress made in developing Zika virus vaccines and antibodies for passive immunization. Copyright © 2017 American Society for Microbiology.

The Antigenic Structure of Zika Virus and Its Relation to Other Flaviviruses: Implications for Infection and Immunoprophylaxis

PubMed Central

Stiasny, Karin

2017-01-01

SUMMARY Zika virus was discovered ∼70 years ago in Uganda and maintained a low profile as a human disease agent in Africa and Asia. Only recently has it caused explosive outbreaks in previously unaffected regions, first in Oceania and then in the Americas since 2015. Of special concern is the newly identified link between congenital malformations (especially microcephaly) and Zika virus infections during pregnancy. At present, it is unclear whether Zika virus changed its pathogenicity or whether the huge number of infections allowed the recognition of a previously cryptic pathogenic property. The purpose of this review is to discuss recent data on the molecular antigenic structure of Zika virus in the context of antibody-mediated neutralization and antibody-dependent enhancement (ADE) of infection, a phenomenon that has been implicated in the development of severe disease caused by the related dengue viruses. Emphasis is given to epitopes of antibodies that potently neutralize Zika virus and also to epitopes that provide antigenic links to other important human-pathogenic flaviviruses such as dengue, yellow fever, West Nile, Japanese encephalitis, and tick-borne encephalitis viruses. The antigenic cross talk between Zika and dengue viruses appears to be of special importance, since they cocirculate in many regions of endemicity and sequential infections are likely to occur frequently. New insights into the molecular antigenic structure of Zika virus and flaviviruses in general have provided the foundation for great progress made in developing Zika virus vaccines and antibodies for passive immunization. PMID:28179396

Functional assignment to JEV proteins using SVM.

PubMed

Sahoo, Ganesh Chandra; Dikhit, Manas Ranjan; Das, Pradeep

2008-01-01

Identification of different protein functions facilitates a mechanistic understanding of Japanese encephalitis virus (JEV) infection and opens novel means for drug development. Support vector machines (SVM), useful for predicting the functional class of distantly related proteins, is employed to ascribe a possible functional class to Japanese encephalitis virus protein. Our study from SVMProt and available JE virus sequences suggests that structural and nonstructural proteins of JEV genome possibly belong to diverse protein functions, are expected to occur in the life cycle of JE virus. Protein functions common to both structural and non-structural proteins are iron-binding, metal-binding, lipid-binding, copper-binding, transmembrane, outer membrane, channels/Pores - Pore-forming toxins (proteins and peptides) group of proteins. Non-structural proteins perform functions like actin binding, zinc-binding, calcium-binding, hydrolases, Carbon-Oxygen Lyases, P-type ATPase, proteins belonging to major facilitator family (MFS), secreting main terminal branch (MTB) family, phosphotransfer-driven group translocators and ATP-binding cassette (ABC) family group of proteins. Whereas structural proteins besides belonging to same structural group of proteins (capsid, structural, envelope), they also perform functions like nuclear receptor, antibiotic resistance, RNA-binding, DNA-binding, magnesium-binding, isomerase (intra-molecular), oxidoreductase and participate in type II (general) secretory pathway (IISP).

Functional assignment to JEV proteins using SVM

PubMed Central

Sahoo, Ganesh Chandra; Dikhit, Manas Ranjan; Das, Pradeep

2008-01-01

Identification of different protein functions facilitates a mechanistic understanding of Japanese encephalitis virus (JEV) infection and opens novel means for drug development. Support vector machines (SVM), useful for predicting the functional class of distantly related proteins, is employed to ascribe a possible functional class to Japanese encephalitis virus protein. Our study from SVMProt and available JE virus sequences suggests that structural and nonstructural proteins of JEV genome possibly belong to diverse protein functions, are expected to occur in the life cycle of JE virus. Protein functions common to both structural and non-structural proteins are iron-binding, metal-binding, lipid-binding, copper-binding, transmembrane, outer membrane, channels/Pores - Pore-forming toxins (proteins and peptides) group of proteins. Non-structural proteins perform functions like actin binding, zinc-binding, calcium-binding, hydrolases, Carbon-Oxygen Lyases, P-type ATPase, proteins belonging to major facilitator family (MFS), secreting main terminal branch (MTB) family, phosphotransfer-driven group translocators and ATP-binding cassette (ABC) family group of proteins. Whereas structural proteins besides belonging to same structural group of proteins (capsid, structural, envelope), they also perform functions like nuclear receptor, antibiotic resistance, RNA-binding, DNA-binding, magnesium-binding, isomerase (intra-molecular), oxidoreductase and participate in type II (general) secretory pathway (IISP). PMID:19052658

Journal of Special Operations Medicine. Volume 11, Edition 1, Winter 2011

DTIC Science & Technology

2011-01-01

encephalitis, Japanese encephalitis (in Asia) or encephalitis from other herpes viruses. Meningitis, especially if caused by tubercu- losis, may have a...recovering from economic depression. He avoided pre-war hype. Following the attack of Japanese forces against U.S. forces at Pearl Harbor, he...radio, and in literature and cinema . The focal point of understanding presented by the au- thor offers contemporary readers insight into wartime

Cross-neutralisation of viruses of the tick-borne encephalitis complex following tick-borne encephalitis vaccination and/or infection.

PubMed

McAuley, Alexander J; Sawatsky, Bevan; Ksiazek, Thomas; Torres, Maricela; Korva, Miša; Lotrič-Furlan, Stanka; Avšič-Županc, Tatjana; von Messling, Veronika; Holbrook, Michael R; Freiberg, Alexander N; Beasley, David W C; Bente, Dennis A

2017-01-01

The tick-borne encephalitis complex contains a number of flaviviruses that share close genetic homology, and are responsible for significant human morbidity and mortality with widespread geographical range. Although many members of this complex have been recognised for decades, licenced human vaccines with broad availability are only available for tick-borne encephalitis virus. While tick-borne encephalitis virus vaccines have been demonstrated to induce significant protective immunity, as determined by virus-neutralisation titres, vaccine breakthrough (clinical infection following complete vaccination), has been described. The aim of this study was to confirm the cross-neutralisation of tick-borne flaviviruses using mouse immune ascitic fluids, and to determine the magnitude of cross-neutralising antibody titres in sera from donors following tick-borne encephalitis vaccination, infection, and vaccine breakthrough. The results demonstrate that there is significant cross-neutralisation of representative members of the tick-borne encephalitis complex following vaccination and/or infection, and that the magnitude of immune responses varies based upon the exposure type. Donor sera successfully neutralised most of the viruses tested, with 85% of vaccinees neutralising Kyasanur forest disease virus and 73% of vaccinees neutralising Alkhumra virus. By contrast, only 63% of vaccinees neutralised Powassan virus, with none of these neutralisation titres exceeding 1:60. Taken together, the data suggest that tick-borne encephalitis virus vaccination may protect against most of the members of the tick-borne encephalitis complex including Kyasanur forest disease virus and Alkhumra virus, but that the neutralisation of Powassan virus following tick-borne encephalitis vaccination is minimal.

Herpes simplex encephalitis with thalamic, brainstem and cerebellar involvement.

PubMed

Garg, Meenal; Kulkarni, Shilpa; Udwadia Hegde, Anaita

2018-04-01

Herpes simplex virus encephalitis is a common and treatable cause of acute encephalitis in all age groups. Certain radiological features such as temporal parenchymal involvement facilitate the diagnosis. The use of herpes simplex virus polymerase chain reaction has expanded the clinical and imaging spectrum. We report the case of a young patient who presented with a movement disorder and predominant involvement of thalami, brainstem and cerebellum on magnetic resonance imaging, and was diagnosed with herpes simplex virus encephalitis. Differentiation from Japanese encephalitis may be difficult in these patients, especially in endemic areas, and may necessitate the use of relevant investigations in all patients.

9 CFR 121.3 - VS select agents and toxins.

Code of Federal Regulations, 2011 CFR

2011-01-01

... AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS POSSESSION, USE, AND...-mouth disease virus; Goat pox virus; Japanese encephalitis virus; Lumpy skin disease virus; Malignant...

9 CFR 121.3 - VS select agents and toxins.

Code of Federal Regulations, 2012 CFR

2012-01-01

... AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS POSSESSION, USE, AND...-mouth disease virus; Goat pox virus; Japanese encephalitis virus; Lumpy skin disease virus; Malignant...

Molecular detection and genotyping of Japanese Encephalitis Virus in mosquitoes during a 2010 outbreak in the Republic of Korea

USGS Publications Warehouse

Seo, Hyun-Ji; Kim, Heung Chul; Klein, Terry A.; Ramey, Andrew M.; Lee, Ji-Hyee; Kyung, Soon-Goo; Park, Jee-Yong; Cho, In-Soo; Yeh, Jung-Yong

2013-01-01

Japanese encephalitis virus (JEV), a mosquito-borne zoonotic pathogen, is one of the major causes of viral encephalitis. To reduce the impact of Japanese encephalitis among children in the Republic of Korea (ROK), the government established a mandatory vaccination program in 1967. Through the efforts of this program only 0-7 (mean 2.1) cases of Japanese encephalitis were reported annually in the ROK during the period of 1984-2009. However, in 2010 there was an outbreak of 26 confirmed cases of Japanese encephalitis, including 7 deaths. This represented a >12-fold increase in the number of confirmed cases of Japanese encephalitis in the ROK as compared to the mean number reported over the last 26 years and a 3.7-fold increase over the highest annual number of cases during this same period (7 cases). Surveillance of adult mosquitoes was conducted during the 2010 outbreak of Japanese encephalitis in the ROK. A total of 6,328 culicine mosquitoes belonging to 12 species from 5 genera were collected at 6 survey sites from June through October 2010 and assayed by reverse-transcription polymerase chain reaction (RT-PCR) for the presence of JEV. A total of 34/371 pooled samples tested positive for JEV (29/121 Culex tritaeniorhynchus, 4/64 Cx. pipiens, and 1/26 Cx. bitaeniorhynchus) as confirmed by sequencing of the pre-membrane and envelope protein coding genes. The maximum likelihood estimates of JEV positive individuals per 1,000 culicine vectors for Cx. tritaeniorhynchus, Cx. pipiens, and Cx. bitaeniorhynchus were 11.8, 5.6, and 2.8, respectively. Sequences of the JEV pre-membrane and envelope protein coding genes amplified from the culicine mosquitoes by RT-PCR were compared with those of JEV genotypes I-V. Phylogenetic analyses support the detection of a single genotype (I) among samples collected from the ROK in 2010.

Arboviruses associated with human disease in Australia.

PubMed

Russell, R C; Dwyer, D E

2000-11-01

Mosquito-borne arboviruses are an important public health issue in Australia. The alphaviruses Ross River and Barmah Forest virus are widespread and active annually, and cause debilitating polyarthritis. The flaviviruses Murray Valley encephalitis, Kunjin and Japanese encephalitis virus are restricted in distribution and activity but may cause life-threatening illness, and dengue viruses are active in some areas.

World Reference Center for Arboviruses

DTIC Science & Technology

1991-05-08

Japanese encephalitis virus and acted as sentinels. By molecular hniques it was shown that the dengue-2 viruses in Venezuela and Brazil are very...12 A. Molecular epidemiology of dengue viruses ................... 12 B. Vaccinia virus recombinants expressing Japanese...of Kagoshima virus (strain KC-05Y84) to the Palyam group. Plaque reduction neutralization tests were done with eight viruses of the Palyam serogroup

Adaptor protein complexes-1 and 3 are involved at distinct stages of flavivirus life-cycle

PubMed Central

Agrawal, Tanvi; Schu, Peter; Medigeshi, Guruprasad R.

2013-01-01

Intracellular protein trafficking pathways are hijacked by viruses at various stages of viral life-cycle. Heterotetrameric adaptor protein complexes (APs) mediate vesicular trafficking at distinct intracellular sites and are essential for maintaining the organellar homeostasis. In the present study, we studied the effect of AP-1 and AP-3 deficiency on flavivirus infection in cells functionally lacking these proteins. We show that AP-1 and AP-3 participate in flavivirus life-cycle at distinct stages. AP-3-deficient cells showed delay in initiation of Japanese encephalitis virus and dengue virus RNA replication, which resulted in reduction of infectious virus production. AP-3 was found to colocalize with RNA replication compartments in infected wild-type cells. AP-1 deficiency affected later stages of dengue virus infection where increased intracellular accumulation of infectious virus was observed. Therefore, our results propose a novel role for AP-1 and AP-3 at distinct stages of infection of some of the RNA viruses. PMID:23657274

Adaptor protein complexes-1 and 3 are involved at distinct stages of flavivirus life-cycle.

PubMed

Agrawal, Tanvi; Schu, Peter; Medigeshi, Guruprasad R

2013-01-01

Intracellular protein trafficking pathways are hijacked by viruses at various stages of viral life-cycle. Heterotetrameric adaptor protein complexes (APs) mediate vesicular trafficking at distinct intracellular sites and are essential for maintaining the organellar homeostasis. In the present study, we studied the effect of AP-1 and AP-3 deficiency on flavivirus infection in cells functionally lacking these proteins. We show that AP-1 and AP-3 participate in flavivirus life-cycle at distinct stages. AP-3-deficient cells showed delay in initiation of Japanese encephalitis virus and dengue virus RNA replication, which resulted in reduction of infectious virus production. AP-3 was found to colocalize with RNA replication compartments in infected wild-type cells. AP-1 deficiency affected later stages of dengue virus infection where increased intracellular accumulation of infectious virus was observed. Therefore, our results propose a novel role for AP-1 and AP-3 at distinct stages of infection of some of the RNA viruses.

Insights into host-finding by Culex mosquitoes: New tools for surveillance?

USDA-ARS?s Scientific Manuscript database

Culex mosquitoes are important vectors of pathogens and parasites causing diseases such as West Nile virus, St. Louis encephalitis, Japanese encephalitis, Venezuelan equine encephalitis and bancroftian filariasis. Surveillance of these species is based on traps using conventional mosquito attractan...

A High-Performance Multiplex Immunoassay for Serodiagnosis of Flavivirus-Associated Neurological Diseases in Horses

PubMed Central

Beck, Cécile; Desprès, Philippe; Paulous, Sylvie; Vanhomwegen, Jessica; Lowenski, Steeve; Nowotny, Norbert; Durand, Benoit; Garnier, Annabelle; Blaise-Boisseau, Sandra; Guitton, Edouard; Yamanaka, Takashi; Zientara, Stéphan; Lecollinet, Sylvie

2015-01-01

West Nile virus (WNV), Japanese encephalitis virus (JEV), and tick-borne encephalitis virus (TBEV) are flaviviruses responsible for severe neuroinvasive infections in humans and horses. The confirmation of flavivirus infections is mostly based on rapid serological tests such as enzyme-linked immunosorbent assays (ELISAs). These tests suffer from poor specificity, mainly due to antigenic cross-reactivity among flavivirus members. Robust diagnosis therefore needs to be validated through virus neutralisation tests (VNTs) which are time-consuming and require BSL3 facilities. The flavivirus envelope (E) glycoprotein ectodomain is composed of three domains (D) named DI, DII, and DIII, with EDIII containing virus-specific epitopes. In order to improve the serological differentiation of flavivirus infections, the recombinant soluble ectodomain of WNV E (WNV.sE) and EDIIIs (rEDIIIs) of WNV, JEV, and TBEV were synthesised using the Drosophila S2 expression system. Purified antigens were covalently bonded to fluorescent beads. The microspheres coupled to WNV.sE or rEDIIIs were assayed with about 300 equine immune sera from natural and experimental flavivirus infections and 172 nonimmune equine sera as negative controls. rEDIII-coupled microspheres captured specific antibodies against WNV, TBEV, or JEV in positive horse sera. This innovative multiplex immunoassay is a powerful alternative to ELISAs and VNTs for veterinary diagnosis of flavivirus-related diseases. PMID:26457301

Specificities of Human CD4+ T Cell Responses to an Inactivated Flavivirus Vaccine and Infection: Correlation with Structure and Epitope Prediction

PubMed Central

Schwaiger, Julia; Aberle, Judith H.; Stiasny, Karin; Knapp, Bernhard; Schreiner, Wolfgang; Fae, Ingrid; Fischer, Gottfried; Scheinost, Ondrej; Chmelik, Vaclav

2014-01-01

ABSTRACT Tick-borne encephalitis (TBE) virus is endemic in large parts of Europe and Central and Eastern Asia and causes more than 10,000 annual cases of neurological disease in humans. It is closely related to the mosquito-borne yellow fever, dengue, Japanese encephalitis, and West Nile viruses, and vaccination with an inactivated whole-virus vaccine can effectively prevent clinical disease. Neutralizing antibodies are directed to the viral envelope protein (E) and an accepted correlate of immunity. However, data on the specificities of CD4+ T cells that recognize epitopes in the viral structural proteins and thus can provide direct help to the B cells producing E-specific antibodies are lacking. We therefore conducted a study on the CD4+ T cell response against the virion proteins in vaccinated people in comparison to TBE patients. The data obtained with overlapping peptides in interleukin-2 (IL-2) enzyme-linked immunosorbent spot (ELISpot) assays were analyzed in relation to the three-dimensional structures of the capsid (C) and E proteins as well as to epitope predictions based on major histocompatibility complex (MHC) class II peptide affinities. In the C protein, peptides corresponding to two out of four alpha helices dominated the response in both vaccinees and patients, whereas in the E protein concordance of immunodominance was restricted to peptides of a single domain (domain III). Epitope predictions were much better for C than for E and were especially erroneous for the transmembrane regions. Our data provide evidence for a strong impact of protein structural features that influence peptide processing, contributing to the discrepancies observed between experimentally determined and computer-predicted CD4+ T cell epitopes. IMPORTANCE Tick-borne encephalitis virus is endemic in large parts of Europe and Asia and causes more than 10,000 annual cases of neurological disease in humans. It is closely related to yellow fever, dengue, Japanese encephalitis, and West Nile viruses, and vaccination with an inactivated vaccine can effectively prevent disease. Both vaccination and natural infection induce the formation of antibodies to a viral surface protein that neutralize the infectivity of the virus and mediate protection. B lymphocytes synthesizing these antibodies require help from other lymphocytes (helper T cells) which recognize small peptides derived from proteins contained in the viral particle. Which of these peptides dominate immune responses to vaccination and infection, however, was unknown. In our study we demonstrate which parts of the proteins contribute most strongly to the helper T cell response, highlight specific weaknesses of currently available approaches for their prediction, and demonstrate similarities and differences between vaccination and infection. PMID:24789782

Outbreak of Powassan encephalitis--Maine and Vermont, 1999-2001.

PubMed

2001-09-07

Powassan (POW) virus, a North American tickborne flavivirus related to the Eastern Hemisphere's tickborne encephalitis viruses, was first isolated from a patient with encephalitis in 1958. During 1958-1998, 27 human POW encephalitis cases were reported from Canada and the northeastern United States. During September 1999-July 2001, four Maine and Vermont residents with encephalitis were found to be infected with POW virus. These persons were tested for other arbovirus infections found in the northeast after testing for West Nile virus (WNV) infection was negative. This report describes these four cases, summarizes the results of ecologic investigations, and discusses a potential association between ticks that infest medium-sized mammals and the risk for human exposure to POW virus. The findings underscore the need for personal protective measures to prevent tick bites and continued encephalitis surveillance.

Diagnosis of Zika Virus Infection by Peptide Array and Enzyme-Linked Immunosorbent Assay

PubMed Central

Caciula, Adrian; Price, Adam; Thakkar, Riddhi; Ng, James; Chauhan, Lokendra V.; Jain, Komal; Che, Xiaoyu; Espinosa, Diego A.; Montoya Cruz, Magelda; Balmaseda, Angel; Sullivan, Eric H.; Patel, Jigar J.; Jarman, Richard G.; Rakeman, Jennifer L.; Egan, Christina T.; Reusken, Chantal B. E. M.; Koopmans, Marion P. G.; Harris, Eva; Tokarz, Rafal; Briese, Thomas

2018-01-01

ABSTRACT Zika virus (ZIKV) is implicated in fetal stillbirth, microcephaly, intracranial calcifications, and ocular anomalies following vertical transmission from infected mothers. In adults, infection may trigger autoimmune inflammatory polyneuropathy. Transmission most commonly follows the bite of infected Aedes mosquitoes but may also occur through sexual intercourse or receipt of blood products. Definitive diagnosis through detection of viral RNA is possible in serum or plasma within 10 days of disease onset, in whole blood within 3 weeks of onset, and in semen for up to 3 months. Serological diagnosis is nonetheless critical because few patients have access to molecular diagnostics during the acute phase of infection and infection may be associated with only mild or inapparent disease that does not prompt molecular testing. Serological diagnosis is confounded by cross-reactivity of immune sera with other flaviviruses endemic in the areas where ZIKV has recently emerged. Accordingly, we built a high-density microarray comprising nonredundant 12-mer peptides that tile, with one-residue overlap, the proteomes of Zika, dengue, yellow fever, West Nile, Ilheus, Oropouche, and chikungunya viruses. Serological analysis enabled discovery of a ZIKV NS2B 20-residue peptide that had high sensitivity (96.0%) and specificity (95.9%) versus natural infection with or vaccination against dengue, chikungunya, yellow fever, West Nile, tick-borne encephalitis, or Japanese encephalitis virus in a microarray assay and an enzyme-linked immunosorbent assay (ELISA) of early-convalescent-phase sera (2 to 3 weeks after onset of symptomatic infection). PMID:29511073

Neuro-Immune Mechanisms in Response to Venezuelan Equine Encephalitis Virus Infection

DTIC Science & Technology

2000-01-01

iii ABSTRACT NEURO-IMMUNE MECHANISMS IN RESPONSE TO VENEZUELAN EQUINE ENCEPHALITIS VIRUS INFECTION Major Bruce A. Schoneboom directed by Franziska B...Grieder, DVM, Ph.D., Assistant Professor of Microbiology and Immunology, Molecular and Cellular Biology, and Neuroscience Venezuelan equine ...3. DATES COVERED - 4. TITLE AND SUBTITLE NEURO-IMMUNE MECHANISMS IN RESPONSE TO VENEZUELAN EQUINE ENCEPHALITIS VIRUS INFECTION 5a. CONTRACT

Protein Interactions during the Flavivirus and Hepacivirus Life Cycle.

PubMed

Gerold, Gisa; Bruening, Janina; Weigel, Bettina; Pietschmann, Thomas

2017-04-01

Protein-protein interactions govern biological functions in cells, in the extracellular milieu, and at the border between cells and extracellular space. Viruses are small intracellular parasites and thus rely on protein interactions to produce progeny inside host cells and to spread from cell to cell. Usage of host proteins by viruses can have severe consequences e.g. apoptosis, metabolic disequilibria, or altered cell proliferation and mobility. Understanding protein interactions during virus infection can thus educate us on viral infection and pathogenesis mechanisms. Moreover, it has led to important clinical translations, including the development of new therapeutic and vaccination strategies. Here, we will discuss protein interactions of members of the Flaviviridae family, which are small enveloped RNA viruses. Dengue virus, Zika virus and hepatitis C virus belong to the most prominent human pathogenic Flaviviridae With a genome of roughly ten kilobases encoding only ten viral proteins, Flaviviridae display intricate mechanisms to engage the host cell machinery for their purpose. In this review, we will highlight how dengue virus, hepatitis C virus, Japanese encephalitis virus, tick-borne encephalitis virus, West Nile virus, yellow fever virus, and Zika virus proteins engage host proteins and how this knowledge helps elucidate Flaviviridae infection. We will specifically address the protein composition of the virus particle as well as the protein interactions during virus entry, replication, particle assembly, and release from the host cell. Finally, we will give a perspective on future challenges in Flaviviridae interaction proteomics and why we believe these challenges should be met. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Regulation of Apoptosis during Flavivirus Infection

PubMed Central

Okamoto, Toru; Suzuki, Tatsuya; Kusakabe, Shinji; Tokunaga, Makoto; Hirano, Junki; Miyata, Yuka; Matsuura, Yoshiharu

2017-01-01

Apoptosis is a type of programmed cell death that regulates cellular homeostasis by removing damaged or unnecessary cells. Its importance in host defenses is highlighted by the observation that many viruses evade, obstruct, or subvert apoptosis, thereby blunting the host immune response. Infection with Flaviviruses such as Japanese encephalitis virus (JEV), Dengue virus (DENV) and West Nile virus (WNV) has been shown to activate several signaling pathways such as endoplasmic reticulum (ER)-stress and AKT/PI3K pathway, resulting in activation or suppression of apoptosis in virus-infected cells. On the other hands, expression of some viral proteins induces or protects apoptosis. There is a discrepancy between induction and suppression of apoptosis during flavivirus infection because the experimental situation may be different, and strong links between apoptosis and other types of cell death such as necrosis may make it more difficult. In this paper, we review the effects of apoptosis on viral propagation and pathogenesis during infection with flaviviruses. PMID:28846635

Protective immunity to Japanese encephalitis virus associated with anti-NS1 antibodies in a mouse model.

PubMed

Li, Yize; Counor, Dorian; Lu, Peng; Duong, Veasna; Yu, Yongxin; Deubel, Vincent

2012-07-24

Japanese encephalitis virus (JEV) is a major mosquito-borne pathogen that causes viral encephalitis throughout Asia. Vaccination with an inactive JEV particle or attenuated virus is an efficient preventative measure for controlling infection. Flavivirus NS1 protein is a glycoprotein secreted during viral replication that plays multiple roles in the viral life cycle and pathogenesis. Utilizing JEV NS1 as an antigen in viral vectors induces a limited protective immune response against infection. Previous studies using E. coli-expressed JEV NS1 to immunize mice induced protection against lethal challenge; however, the protection mechanism through cellular and humoral immune responses was not described. JEV NS1 was expressed in and purified from Drosophila S2 cells in a native glycosylated multimeric form, which induced T-cell and antibody responses in immunized C3H/HeN mice. Mice vaccinated with 1 μg NS1 with or without water-in-oil adjuvant were partially protected against viral challenge and higher protection was observed in mice with higher antibody titers. IgG1 was preferentially elicited by an adjuvanted NS1 protein, whereas a larger load of IFN-γ was produced in splenocytes from mice immunized with aqueous NS1. Mice that passively received anti-NS1 mouse polyclonal immune sera were protected, and this phenomenon was dose-dependent, whereas protection was low or delayed after the passive transfer of anti-NS1 MAbs. The purified NS1 subunit induced protective immunity in relation with anti-NS1 IgG1 antibodies. NS1 protein efficiently stimulated Th1-cell proliferation and IFN-γ production. Protection against lethal challenge was elicited by passive transfer of anti-NS1 antisera, suggesting that anti-NS1 antibodies play a substantial role in anti-viral immunity.

ST. LOUIS ENCEPHALITIS

PubMed Central

Smith, Margaret G.; Blattner, Russell J.; Heys, Florence M.

1947-01-01

Transmission of the virus of St. Louis encephalitis to normal chickens by the bite of infected mites (Dermanyssus gallinae) has been demonstrated. Both experimentally infected and naturally infected mites were shown to be capable of transferring the virus of St. Louis encephalitis to chickens by bite. Virus is present in the blood of such chickens in small amounts, so that demonstration of viremia was possible only by utilizing chorioallantoic passage in hens' eggs. However, there is sufficient virus present in the blood for uninfected chicken mites to acquire the virus by feeding on chickens in which viremia has resulted from previous bite of infected mites. Thus it has been shown that the arachnid vector Dermanyssus gallinae is capable of transmitting the virus of St. Louis encephalitis to normal chickens by bite and that such chickens can serve as a source of virus for uninfected mites. PMID:19871673

A rapid and quantitative assay for measuring antibody-mediated neutralization of West Nile virus infection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pierson, Theodore C.; Sanchez, Melissa D.; Puffer, Bridget A.

2006-03-01

West Nile virus (WNV) is a neurotropic flavivirus within the Japanese encephalitis antigenic complex that is responsible for causing West Nile encephalitis in humans. The surface of WNV virions is covered by a highly ordered icosahedral array of envelope proteins that is responsible for mediating attachment and fusion with target cells. These envelope proteins are also primary targets for the generation of neutralizing antibodies in vivo. In this study, we describe a novel approach for measuring antibody-mediated neutralization of WNV infection using virus-like particles that measure infection as a function of reporter gene expression. These reporter virus particles (RVPs) aremore » produced by complementation of a sub-genomic replicon with WNV structural proteins provided in trans using conventional DNA expression vectors. The precision and accuracy of this approach stem from an ability to measure the outcome of the interaction between antibody and viral antigens under conditions that satisfy the assumptions of the law of mass action as applied to virus neutralization. In addition to its quantitative strengths, this approach allows the production of WNV RVPs bearing the prM-E proteins of different WNV strains and mutants, offering considerable flexibility for the study of the humoral immune response to WNV in vitro. WNV RVPs are capable of only a single round of infection, can be used under BSL-2 conditions, and offer a rapid and quantitative approach for detecting virus entry and its inhibition by neutralizing antibody.« less

Prevalence of antibodies to Japanese encephalitis virus among pigs in Bali and East Java, Indonesia, 2008.

PubMed

Yamanaka, Atsushi; Mulyatno, Kris Cahyo; Susilowati, Helen; Hendrianto, Eryk; Utsumi, Takako; Amin, Mochamad; Lusida, Maria Inge; Soegijanto, Soegeng; Konishi, Eiji

2010-01-01

Japanese encephalitis virus (JEV) is a fatal disease in Asia. Pigs are considered to be the effective amplifying host for JEV in the peridomestic environment. Bali Island and Java Island in Indonesia provide a model to assess the effect of pigs on JEV transmission, since the pig density is nearly 100-fold higher in Bali than Java, while the geographic and climatologic environments are equivalent in these areas. We surveyed antibodies to JEV among 123 pigs in Mengwi (Bali) and 96 pigs in Tulungagung (East Java) in 2008 by the hemagglutination-inhibition (HAI) test. Overall prevalences were 49% in Bali and 6% in Java, with a significant difference between them (P < 0.001). Monthly infection rates estimated from age-dependent antibody prevalences were 11% in Bali and 2% in Java. In addition, 2-mercaptoethanol-sensitive antibodies were found only from Bali samples. Further, the average HAI antibody titer obtained from positive samples was significantly higher in Bali (1:52) than Java (1:10; P < 0.001). These results indicated that JEV transmission in nature is more active in Bali than East Java.

Estimating the Burden of Japanese Encephalitis Virus and Other Encephalitides in Countries of the Mekong Region

PubMed Central

Tarantola, Arnaud; Goutard, Flavie; Newton, Paul; de Lamballerie, Xavier; Lortholary, Olivier; Cappelle, Julien; Buchy, Philippe

2014-01-01

Diverse aetiologies of viral and bacterial encephalitis are widely recognized as significant yet neglected public health issues in the Mekong region. A robust analysis of the corresponding health burden is lacking. We retrieved 75 articles on encephalitis in the region published in English or in French from 1965 through 2011. Review of available data demonstrated that they are sparse and often derived from hospital-based studies with significant recruitment bias. Almost half (35 of 75) of articles were on Japanese encephalitis virus (JEV) alone or associated with dengue. In the Western Pacific region the WHO reported 30,000–50,000 annual JEV cases (15,000 deaths) between 1966 and 1996 and 4,633 cases (200 deaths) in 2008, a decline likely related to the introduction of JEV vaccination in China, Vietnam, or Thailand since the 1980s. Data on dengue, scrub typhus and rabies encephalitis, among other aetiologies, are also reviewed and discussed. Countries of the Mekong region are undergoing profound demographic, economic and ecological change. As the epidemiological aspects of Japanese encephalitis (JE) are transformed by vaccination in some countries, highly integrated expert collaborative research and objective data are needed to identify and prioritize the human health, animal health and economic burden due to JE and other pathogens associated with encephalitides. PMID:24498443

Fatal Tick-Borne Encephalitis Virus Infections Caused by Siberian and European Subtypes, Finland, 2015.

PubMed

Kuivanen, Suvi; Smura, Teemu; Rantanen, Kirsi; Kämppi, Leena; Kantonen, Jonas; Kero, Mia; Jääskeläinen, Anu; Jääskeläinen, Anne J; Sane, Jussi; Myllykangas, Liisa; Paetau, Anders; Vapalahti, Olli

2018-05-01

In most locations except for Russia, tick-borne encephalitis is mainly caused by the European virus subtype. In 2015, fatal infections caused by European and Siberian tick-borne encephalitis virus subtypes in the same Ixodes ricinus tick focus in Finland raised concern over further spread of the Siberian subtype among widespread tick species.

Development and characterization of polyclonal peptide antibodies for the detection of Yellow fever virus proteins.

PubMed

Stock, N K; Escadafal, C; Achazi, K; Cissé, M; Niedrig, M

2015-09-15

There is still a considerable need for development of new tools and methods detecting specific viral proteins for the diagnosis and pathogenesis study of the Yellow fever virus (YFV). This study aimed to develop and characterize polyclonal peptide antisera for detection of YFV-C and -NS1 proteins. The antisera were used further to investigate NS1 protein expression during YFV infection in mammalian cells. YFV target proteins were detected by all antisera in western blot and immunofluorescence assays. No cross-reactivity was observed with Dengue virus, West Nile virus, Tick-borne encephalitis virus and Japanese encephalitis virus. Nuclear localization of the YFV-C protein was demonstrated for the first time. Experiments investigating NS1 expression suggested a potential use of the YFV-NS1 antisera for development of diagnostic approaches targeting the secreted form of the NS1 protein. The antisera described in this study offer new possibilities for use in YFV research and for the development of novel diagnostic tests. Copyright © 2015 Elsevier B.V. All rights reserved.

Functionality of Dengue Virus Specific Memory T Cell Responses in Individuals Who Were Hospitalized or Who Had Mild or Subclinical Dengue Infection

PubMed Central

Jeewandara, Chandima; Adikari, Thiruni N.; Gomes, Laksiri; Fernando, Samitha; Fernando, R. H.; Perera, M. K. T.; Ariyaratne, Dinuka; Kamaladasa, Achala; Salimi, Maryam; Prathapan, Shamini

2015-01-01

Background Although antibody responses to dengue virus (DENV) in naturally infected individuals have been extensively studied, the functionality of DENV specific memory T cell responses in relation to clinical disease severity is incompletely understood. Methodology/Principal findings Using ex vivo IFNγ ELISpot assays, and by determining cytokines produced in ELISpot supernatants, we investigated the functionality of DENV-specific memory T cell responses in a large cohort of individuals from Sri Lanka (n=338), who were naturally infected and were either hospitalized due to dengue or had mild or sub clinical dengue infection. We found that T cells of individuals with both past mild or sub clinical dengue infection and who were hospitalized produced multiple cytokines when stimulated with DENV-NS3 peptides. However, while DENV-NS3 specific T cells of those with mild/sub clinical dengue infection were more likely to produce only granzyme B (p=0.02), those who were hospitalized were more likely to produce both TNFα and IFNγ (p=0.03) or TNFα alone. We have also investigated the usefulness of a novel T cell based assay, which can be used to determine the past infecting DENV serotype. 92.4% of DENV seropositive individuals responded to at least one DENV serotype of this assay and none of the seronegatives responded. Individuals who were seronegative, but had received the Japanese encephalitis vaccine too made no responses, suggesting that the peptides used in this assay did not cross react with the Japanese encephalitis virus. Conclusions/significance The types of cytokines produced by DENV-specific memory T cells appear to influence the outcome of clinical disease severity. The novel T cell based assay, is likely to be useful in determining the past infecting DENV serotype in immune-epidemiological studies and also in dengue vaccine trials. PMID:25875020

Zoonotic encephalitides caused by arboviruses: transmission and epidemiology of alphaviruses and flaviviruses

PubMed Central

Balasuriya, Udeni B. R.; Lee, Chong-kyo

2014-01-01

In this review, we mainly focus on zoonotic encephalitides caused by arthropod-borne viruses (arboviruses) of the families Flaviviridae (genus Flavivirus) and Togaviridae (genus Alphavirus) that are important in both humans and domestic animals. Specifically, we will focus on alphaviruses (Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus) and flaviviruses (Japanese encephalitis virus and West Nile virus). Most of these viruses were originally found in tropical regions such as Africa and South America or in some regions in Asia. However, they have dispersed widely and currently cause diseases around the world. Global warming, increasing urbanization and population size in tropical regions, faster transportation and rapid spread of arthropod vectors contribute in continuous spreading of arboviruses into new geographic areas causing reemerging or resurging diseases. Most of the reemerging arboviruses also have emerged as zoonotic disease agents and created major public health issues and disease epidemics. PMID:24427764

Zoonotic encephalitides caused by arboviruses: transmission and epidemiology of alphaviruses and flaviviruses.

PubMed

Go, Yun Young; Balasuriya, Udeni B R; Lee, Chong-Kyo

2014-01-01

In this review, we mainly focus on zoonotic encephalitides caused by arthropod-borne viruses (arboviruses) of the families Flaviviridae (genus Flavivirus) and Togaviridae (genus Alphavirus) that are important in both humans and domestic animals. Specifically, we will focus on alphaviruses (Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus) and flaviviruses (Japanese encephalitis virus and West Nile virus). Most of these viruses were originally found in tropical regions such as Africa and South America or in some regions in Asia. However, they have dispersed widely and currently cause diseases around the world. Global warming, increasing urbanization and population size in tropical regions, faster transportation and rapid spread of arthropod vectors contribute in continuous spreading of arboviruses into new geographic areas causing reemerging or resurging diseases. Most of the reemerging arboviruses also have emerged as zoonotic disease agents and created major public health issues and disease epidemics.

Epidemiology of Japanese encephalitis: past, present, and future prospects

PubMed Central

Wang, Huanyu; Liang, Guodong

2015-01-01

Japanese encephalitis (JE) is one of severe viral encephalitis that affects individuals in Asia, western Pacific countries, and northern Australia. Although 67,900 JE cases have been estimated among 24 JE epidemic countries annually, only 10,426 have been reported in 2011. With the establishment of JE surveillance and vaccine use in some countries, the JE incidence rate has decreased; however, serious outbreaks still occur. Understanding JE epidemics and identifying the circulating JE virus genotypes will improve JE prevention and control. This review summarizes the current epidemiology data in these countries. PMID:25848290

Chimeric classical swine fever (CSF)-Japanese encephalitis (JE) viral particles as a non-transmissible bivalent marker vaccine candidate against CSF and JE infections

USDA-ARS?s Scientific Manuscript database

A trans-complemented CSF- JE chimeric viral replicon was constructed using an infectious cDNA clone of the CSF virus (CSFV) Alfort/187 strain. The E2 gene of CSFV Alfort/187 strain was deleted and the resultant plasmid pA187delE2 was inserted by a fragment containing the region coding for a truncate...

Subclinical infection without encephalitis in mice following intranasal exposure to Nipah virus-Malaysia and Nipah virus-Bangladesh.

PubMed

Dups, Johanna; Middleton, Deborah; Long, Fenella; Arkinstall, Rachel; Marsh, Glenn A; Wang, Lin-Fa

2014-06-02

Nipah virus and Hendra virus are closely related and following natural or experimental exposure induce similar clinical disease. In humans, encephalitis is the most serious outcome of infection and, hitherto, research into the pathogenesis of henipavirus encephalitis has been limited by the lack of a suitable model. Recently we reported a wild-type mouse model of Hendra virus (HeV) encephalitis that should facilitate detailed investigations of its neuropathogenesis, including mechanisms of disease recrudescence. In this study we investigated the possibility of developing a similar model of Nipah virus encephalitis. Aged and young adult wild type mice did not develop clinical disease including encephalitis following intranasal exposure to either the Malaysia (NiV-MY) or Bangladesh (NiV-BD) strains of Nipah virus. However viral RNA was detected in lung tissue of mice at euthanasia (21 days following exposure) accompanied by a non-neutralizing antibody response. In a subsequent time course trial this viral RNA was shown to be reflective of an earlier self-limiting and subclinical lower respiratory tract infection through successful virus re-isolation and antigen detection in lung. There was no evidence for viremia or infection of other organs, including brain. Mice develop a subclinical self-limiting lower respiratory tract infection but not encephalitis following intranasal exposure to NiV-BD or NiV-MY. These results contrast with those reported for HeV under similar exposure conditions in mice, demonstrating a significant biological difference in host clinical response to exposure with these viruses. This finding provides a new platform from which to explore the viral and/or host factors that determine the neuroinvasive ability of henipaviruses.

Molecular targets for flavivirus drug discovery

PubMed Central

Sampath, Aruna; Padmanabhan, R.

2009-01-01

Flaviviruses are a major cause of infectious disease in humans. Dengue virus causes an estimated 50 million cases of febrile illness each year, including an increasing number of cases of hemorrhagic fever. West Nile virus, which recently spread from the Mediterranean basin to the Western Hemisphere, now causes thousands of sporadic cases of encephalitis annually. Despite the existence of licensed vaccines, yellow fever, Japanese encephalitis and tick-borne encephalitis also claim many thousands of victims each year across their vast endemic areas. Antiviral therapy could potentially reduce morbidity and mortality from flavivirus infections, but no effective drugs are currently available. This article introduces a collection of papers in Antiviral Research on molecular targets for flavivirus antiviral drug design and murine models of dengue virus disease that aims to encourage drug development efforts. After reviewing the flavivirus replication cycle, we discuss the envelope glycoprotein, NS3 protease, NS3 helicase, NS5 methyltransferase and NS5 RNA-dependent RNA polymerase as potential drug targets, with special attention being given to the viral protease. The other viral proteins are the subject of individual articles in the journal. Together, these papers highlight current status of drug discovery efforts for flavivirus diseases and suggest promising areas for further research. PMID:18796313

Defining Hsp70 Subnetworks in Dengue Virus Replication Reveals Key Vulnerability in Flavivirus Infection

PubMed Central

Taguwa, Shuhei; Maringer, Kevin; Li, Xiaokai; Bernal-Rubio, Dabeiba; Rauch, Jennifer N.; Gestwicki, Jason E.; Andino, Raul; Fernandez-Sesma, Ana; Frydman, Judith

2015-01-01

Summary Viral protein homeostasis depends entirely on the machinery of the infected cell. Accordingly, viruses can illuminate the interplay between cellular proteostasis components and their distinct substrates. Here we define how the Hsp70 chaperone network mediates the dengue virus life cycle. Cytosolic Hsp70 isoforms are required at distinct steps of the viral cycle, including entry, RNA replication and virion biogenesis. Hsp70 function at each step is specified by nine distinct DNAJ cofactors. Of these, DnaJB11 relocalizes to virus-induced replication complexes to promote RNA synthesis, while DnaJB6 associates with capsid protein and facilitates virion biogenesis. Importantly, an allosteric Hsp70 inhibitor, JG40, potently blocks infection of different dengue serotypes in human primary blood cells without eliciting viral resistance or exerting toxicity to the host cells. JG40 also blocks replication of other medically-important flaviviruses including yellow fever, West Nile and Japanese encephalitis viruses. Thus, targeting host Hsp70 subnetworks provides a path for broad-spectrum antivirals. PMID:26582131

CCL2, but not its receptor, is essential to restrict immune privileged central nervous system-invasion of Japanese encephalitis virus via regulating accumulation of CD11b(+) Ly-6C(hi) monocytes.

PubMed

Kim, Jin Hyoung; Patil, Ajit Mahadev; Choi, Jin Young; Kim, Seong Bum; Uyangaa, Erdenebileg; Hossain, Ferdaus Mohd Altaf; Park, Sang-Youel; Lee, John Hwa; Kim, Koanhoi; Eo, Seong Kug

2016-10-01

Japanese encephalitis virus (JEV) is a re-emerging zoonotic flavivirus that poses an increasing threat to global health and welfare due to rapid changes in climate and demography. Although the CCR2-CCL2 axis plays an important role in trafficking CD11b(+) Ly-6C(hi) monocytes to regulate immunopathological diseases, little is known about their role in monocyte trafficking during viral encephalitis caused by JEV infection. Here, we explored the role of CCR2 and its ligand CCL2 in JE caused by JEV infection using CCR2- and CCL2-ablated murine models. Somewhat surprisingly, the ablation of CCR2 and CCL2 resulted in starkly contrasting susceptibility to JE. CCR2 ablation induced enhanced resistance to JE, whereas CCL2 ablation highly increased susceptibility to JE. This contrasting regulation of JE progression by CCR2 and CCL2 was coupled to central nervous system (CNS) infiltration of Ly-6C(hi) monocytes and Ly-6G(hi) granulocytes. There was also enhanced expression of CC and CXC chemokines in the CNS of CCL2-ablated mice, which appeared to induce CNS infiltration of these cell populations. However, our data revealed that contrasting regulation of JE in CCR2- and CCL2-ablated mice was unlikely to be mediated by innate natural killer and adaptive T-cell responses. Furthermore, CCL2 produced by haematopoietic stem cell-derived leucocytes played a dominant role in CNS accumulation of Ly-6C(hi) monocytes in infected bone marrow chimeric models, thereby exacerbating JE progression. Collectively, our data indicate that CCL2 plays an essential role in conferring protection against JE caused by JEV infection. In addition, blockage of CCR2, but not CCL2, will aid in the development of strategies for prophylactics and therapeutics of JE. © 2016 John Wiley & Sons Ltd.

Tick-borne encephalitis.

PubMed

Gritsun, T S; Lashkevich, V A; Gould, E A

2003-01-01

Tick-borne encephalitis (TBE) is one of the most dangerous human infections occurring in Europe and many parts of Asia. The etiological agent Tick-borne encephalitis virus (TBEV), is a member of the virus genus Flavivirus, of the family Flaviviridae. TBEV is believed to cause at least 11,000 human cases of encephalitis in Russia and about 3000 cases in the rest of Europe annually. Related viruses within the same group, Louping ill virus (LIV), Langat virus (LGTV) and Powassan virus (POWV), also cause human encephalitis but rarely on an epidemic scale. Three other viruses within the same group, Omsk hemorrhagic fever virus (OHFV), Kyasanur Forest disease virus (KFDV) and Alkhurma virus (ALKV), are closely related to the TBEV complex viruses and tend to cause fatal hemorrhagic fevers rather than encephalitis. This review describes the clinical manifestations associated with TBEV infections, the main molecular-biological properties of these viruses, and the different factors that define the incidence and severity of disease. The role of ticks and their local hosts in the emergence of new virus variants with different pathogenic characteristics is also discussed. This review also contains a brief history of vaccination against TBE including trials with live attenuated vaccine and modern tendencies in developing of vaccine virus strains.

Viperin Restricts Zika Virus and Tick-Borne Encephalitis Virus Replication by Targeting NS3 for Proteasomal Degradation.

PubMed

Panayiotou, Christakis; Lindqvist, Richard; Kurhade, Chaitanya; Vonderstein, Kirstin; Pasto, Jenny; Edlund, Karin; Upadhyay, Arunkumar S; Överby, Anna K

2018-04-01

Flaviviruses are arthropod-borne viruses that constitute a major global health problem, with millions of human infections annually. Their pathogenesis ranges from mild illness to severe manifestations such as hemorrhagic fever and fatal encephalitis. Type I interferons (IFNs) are induced in response to viral infection and stimulate the expression of interferon-stimulated genes (ISGs), including that encoding viperin (virus-inhibitory protein, endoplasmic reticulum associated, IFN inducible), which shows antiviral activity against a broad spectrum of viruses, including several flaviviruses. Here we describe a novel antiviral mechanism employed by viperin against two prominent flaviviruses, tick-borne encephalitis virus (TBEV) and Zika virus (ZIKV). Viperin was found to interact and colocalize with the structural proteins premembrane (prM) and envelope (E) of TBEV, as well as with nonstructural (NS) proteins NS2A, NS2B, and NS3. Interestingly, viperin expression reduced the NS3 protein level, and the stability of the other interacting viral proteins, but only in the presence of NS3. We also found that although viperin interacted with NS3 of mosquito-borne flaviviruses (ZIKV, Japanese encephalitis virus, and yellow fever virus), only ZIKV was sensitive to the antiviral effect of viperin. This sensitivity correlated with viperin's ability to induce proteasome-dependent degradation of NS3. ZIKV and TBEV replication was rescued completely when NS3 was overexpressed, suggesting that the viral NS3 is the specific target of viperin. In summary, we present here a novel antiviral mechanism of viperin that is selective for specific viruses in the genus Flavivirus , affording the possible availability of new drug targets that can be used for therapeutic intervention. IMPORTANCE Flaviviruses are a group of enveloped RNA viruses that cause severe diseases in humans and animals worldwide, but no antiviral treatment is yet available. Viperin, a host protein produced in response to infection, effectively restricts the replication of several flaviviruses, but the exact molecular mechanisms have not been elucidated. Here we have identified a novel mechanism employed by viperin to inhibit the replication of two flaviviruses: tick-borne encephalitis virus (TBEV) and Zika virus (ZIKV). Viperin induced selective degradation via the proteasome of TBEV and ZIKV nonstructural 3 (NS3) protein, which is involved in several steps of the viral life cycle. Furthermore, viperin also reduced the stability of several other viral proteins in a NS3-dependent manner, suggesting a central role of NS3 in viperin's antiflavivirus activity. Taking the results together, our work shows important similarities and differences among the members of the genus Flavivirus and could lead to the possibility of therapeutic intervention. Copyright © 2018 American Society for Microbiology.

Emergence of zoonotic arboviruses by animal trade and migration

PubMed Central

2010-01-01

Arboviruses are transmitted in nature exclusively or to a major extend by arthropods. They belong to the most important viruses invading new areas in the world and their occurrence is strongly influenced by climatic changes due to the life cycle of the transmitting vectors. Several arboviruses have emerged in new regions of the world during the last years, like West Nile virus (WNV) in the Americas, Usutu virus (USUV) in Central Europe, or Rift Valley fever virus (RVFV) in the Arabian Peninsula. In most instances the ways of introduction of arboviruses into new regions are not known. Infections acquired during stays in the tropics and subtropics are diagnosed with increasing frequency in travellers returning from tropical countries, but interestingly no attention is paid on accompanying pet animals or the hematophagous ectoparasites that may still be attached to them. Here we outline the known ecology of the mosquito-borne equine encephalitis viruses (WEEV, EEEV, and VEEV), WNV, USUV, RVFV, and Japanese Encephalitis virus, as well as Tick-Borne Encephalitis virus and its North American counterpart Powassan virus, and will discuss the most likely mode that these viruses could expand their respective geographical range. All these viruses have a different epidemiology as different vector species, reservoir hosts and virus types have adapted to promiscuous and robust or rather very fine-balanced transmission cycles. Consequently, these viruses will behave differently with regard to the requirements needed to establish new endemic foci outside their original geographical ranges. Hence, emphasis is given on animal trade and suitable ecologic conditions, including competent vectors and vertebrate hosts. PMID:20377873

Fever of Unknown Origin in a Patient with Confirmed West Nile Virus Meningoencephalitis

PubMed Central

Sabre, Alexander; Farricielli, Laurie

2014-01-01

West Nile Virus (WNV), an RNA arbovirus and member of the Japanese encephalitis virus antigenic complex, causes a wide range of clinical symptoms, from asymptomatic to encephalitis and meningitis. Nearly all human infections of WNV are due to mosquito bites with birds being the primary amplifying hosts. Advanced age is the most important risk factor for neurological disease leading most often to poor prognosis in those afflicted. We report a case of WNV meningoencephalitis in a 93-year-old Caucasian male who presented with fever of unknown origin (FUO) and nuchal rigidity that rapidly decompensated within 24 h to a persistent altered mental state during inpatient stay. The patient's ELISA antibody titers confirmed pathogenesis of disease by WNV; he given supportive measures and advanced to an excellent recovery. In regard to the approach of FUO, it is important to remain impartial yet insightful to all elements when determining pathogenesis in atypical presentation. PMID:25580318

Acute encephalitis in the immunocompromised individual.

PubMed

Saylor, Deanna; Thakur, Kiran; Venkatesan, Arun

2015-08-01

This article describes recent advances in the diagnosis and management of encephalitis in immunocompromised individuals. Herpes simplex virus (HSV) and varicella zoster virus (VZV) are common causes of encephalitis in immunocompromised individuals, although clinical manifestations may be atypical, and thus challenging to recognize. Recently, an increased incidence of HSV and VZV central nervous system infections has been reported in association with novel immunosuppressive and immunomodulatory treatments. The free-living ameba Balamuthia mandrillaris causes granulomatous encephalitis predominantly in immunocompromised individuals and is associated with nearly uniform fatality. In the setting of organ transplantation, the recipient's immunocompromised state along with the potential for donor-transmitted infections can result in a unique epidemiology of encephalitis, including infection by human herpes virus-6 and BK virus. Recent studies utilizing next-generation sequencing techniques have identified several pathogens, including Leptospira santarosai and a neurotropic astrovirus, as causes of encephalitis in immunocompromised individuals. Diagnosis and management of encephalitis is challenging in immunocompromised individuals, in part because of atypical clinical presentations and the presence of uncommon or novel infectious agents. Unbiased techniques for pathogen discovery are likely to play an increasing role in the diagnosis of central nervous system infections in immunocompromised individuals.

Pathogenesis of Aerosolized Eastern Equine Encephalitis Virus Infection in Guinea Pigs

DTIC Science & Technology

2009-01-01

BioMed CentralVirology Journal ss Approved for public release. Distribution is unlimitedOpen AcceResearch Pathogenesis of aerosolized Eastern Equine ...NJ1959 or ArgM) of eastern equine encephalitis virus (EEEV) at two exclusive particle size distributions. Mice were more susceptible to either strain...fatal human infection and thus should serve as a suitable animal model for aerosol exposure to EEEV. Introduction Eastern equine encephalitis (EEE) virus

ST. LOUIS ENCEPHALITIS

PubMed Central

Smith, Margaret G.; Blattner, Russell J.; Heys, Florence M.

1946-01-01

A colony of chicken mites (Dermanyssus gallinae) was established from a single adult female mite and her offspring. This colony of mites was shown to be free of the virus of St. Louis encephalitis. Infection of mites from this homogeneous colony with the virus of St. Louis encephalitis was accomplished by feeding on chickens having viremia. The virus was recovered as readily from mites which had not been allowed to feed for 8 days as from mites freshly engorged, showing that the demonstration of virus in the mites does not depend on the presence of fresh infective chicken blood. Transovarian passage of the St. Louis virus into the second generation has been demonstrated in mites infected experimentally. The female mite infected as an adult can pass the St. Louis virus through eggs laid after additional feeding on normal blood. Persistence of the virus for a period of 6 months has been shown in a colony of mites infected experimentally in the laboratory. PMID:19871548

Japanese encephalitis: the vectors, ecology and potential for expansion.

PubMed

Pearce, James C; Learoyd, Tristan P; Langendorf, Benjamin J; Logan, James G

2018-05-01

Japanese encephalitis (JE) is a viral disease predominantly located in South East Asia and commonly associated with transmission between amplifying hosts, such as pigs, and the mosquito Culex tritaeniorhynchus, where human infection represents a dead end in the life cycle of the virus. The expansion of JE beyond an Asiatic confine is dependent on a multitude of complex factors that stem back to genetic subtype variation. A complex interplay of the genetic variation and vector competencies combine with variables such as geography, climate change and urbanization. Our understanding of JE is still at an early stage with long-term longitudinal vector surveillance necessary to better understand the dynamics of JE transmission and to characterize the role of potential secondary vectors such as Cx. pipiens and Cx. bitaeniorhynchus. The authors review the vectors indicated in transmission and the ecological, genetic and anthropological factors that affect the disease's range and epidemiology. Monitoring for the presence of JE virus in mosquitoes in general can be used to estimate levels of potential JE exposure, intensity of viral activity and genetic variation of JEV throughout surveyed areas. Increased surveillance and diagnosis of viral encephalitis caused by genotype 5 JE virus is required in particular, with the expansion in epidemiology and disease prevalence in new geographic areas an issue of great concern. Additional studies that measure the impact of vectors (e.g. bionomics and vector competence) in the transmission of JEV and that incorporate environmental factors (e.g. weekly rainfall) are needed to define the roles of Culex species in the viral pathogenesis during outbreak and non-outbreak years.

Prevalence of Neutralizing Antibodies to Japanese Encephalitis Virus among High-Risk Age Groups in South Korea, 2010

PubMed Central

Ju, Young Ran; Han, Myung Guk; Lee, Won-Ja; Jeong, Young Eui

2016-01-01

After an extensive vaccination policy, Japanese encephalitis (JE) was nearly eliminated since the mid-1980s in South Korea. Vaccination in children shifted the affected age of JE patients from children to adults. However, an abrupt increase in JE cases occurred in 2010, and this trend has continued. The present study aimed to investigate the prevalence of neutralizing antibodies to the JE virus (JEV) among high-risk age groups (≥40 years) in South Korea. A plaque reduction neutralization test was conducted to evaluate the prevalence of neutralizing antibodies to JEV in 945 subjects within four age groups (30–39, 40–49, 50–59, and 60–69 years) in 10 provinces. Of the 945 enrolled subjects, 927 (98.1%) exhibited antibodies against JEV. No significant differences were found in the prevalence of neutralizing antibodies according to sex, age, or occupation. However, there were significant differences in the plaque reduction rate according to age and occupation; oldest age group had a higher reduction rate, and subjects who were employed in agriculture or forestry also had a higher value than the other occupations. We also found that three provinces (Gangwon, Jeonnam, and Gyeongnam) had a relatively lower plaque reduction rate than the other locations. In addition, enzyme-linked immunosorbent assays were conducted to determine recent viral infections and 12 (2.2%) subjects were found to have been recently infected by the virus. In conclusion, the present study clearly indicated that the prevalence of neutralizing antibodies has been maintained at very high levels among adult age groups owing to vaccination or natural infections, or both. In the future, serosurveillance should be conducted periodically using more representative samples to better understand the population-level immunity to JE in South Korea. PMID:26807709

Overview of Japanese encephalitis disease and its prevention. Focus on IC51 vaccine (IXIARO®)

PubMed Central

AMICIZIA, D.; ZANGRILLO, F.; LAI, P.L.; IOVINE, M.; PANATTO, D.

2018-01-01

Summary Japanese encephalitis (JE) is a vector-borne disease caused by the Japanese encephalitis virus (JEV). JEV is transmitted by mosquitoes to a wide range of vertebrate hosts, including birds and mammals. Domestic animals, especially pigs, are generally implicated as reservoirs of the virus, while humans are not part of the natural transmission cycle and cannot pass the virus to other hosts. Although JEV infection is very common in endemic areas (many countries in Asia), less than 1% of people affected develop clinical disease, and severe disease affects about 1 case per 250 JEV infections. Although rare, severe disease can be devastating; among the 30,000-50,000 global cases per year, approximately 20-30% of patients die and 30-50% of survivors develop significant neurological sequelae. JE is a significant public health problem for residents in endemic areas and may constitute a substantial risk for travelers to these areas. The epidemiology of JE and its risk to travelers have changed, and continue to evolve. The rapid economic growth of Asian countries has led to a surge in both inbound and outbound travel, making Asia the second most-visited region in the world after Europe, with 279 million international travelers in 2015. The top destination is China, followed by Thailand, Hong Kong, Malaysia and Japan, and the number of travelers is forecast to reach 535 million by 2030 (+ 4.9% per year). Because of the lack of treatment and the infeasibility of eliminating the vector, vaccination is recognized as the most efficacious means of preventing JE. The IC51 vaccine (IXIARO®) is a purified, inactivated, whole virus vaccine against JE. It is safe, well tolerated, efficacious and can be administered to children, adults and the elderly. The vaccination schedule involves administering 2 doses four weeks apart. For adults, a rapid schedule (0-7 days) is available, which could greatly enhance the feasibility of its use. Healthcare workers should inform both short- and long-term travelers of the risk of JE in each period of the year and recommend vaccination. Indeed, it has been shown that short-term travelers are also at risk, not only in rural environments, but also in cities and coastal towns, especially in tourist localities where excursions to country areas are organized.

[Multiplex real-time PCR method for rapid detection of Marburg virus and Ebola virus].

PubMed

Yang, Yu; Bai, Lin; Hu, Kong-Xin; Yang, Zhi-Hong; Hu, Jian-Ping; Wang, Jing

2012-08-01

Marburg virus and Ebola virus are acute infections with high case fatality rates. A rapid, sensitive detection method was established to detect Marburg virus and Ebola virus by multiplex real-time fluorescence quantitative PCR. Designing primers and Taqman probes from highly conserved sequences of Marburg virus and Ebola virus through whole genome sequences alignment, Taqman probes labeled by FAM and Texas Red, the sensitivity of the multiplex real-time quantitative PCR assay was optimized by evaluating the different concentrations of primers and Probes. We have developed a real-time PCR method with the sensitivity of 30.5 copies/microl for Marburg virus positive plasmid and 28.6 copies/microl for Ebola virus positive plasmids, Japanese encephalitis virus, Yellow fever virus, Dengue virus were using to examine the specificity. The Multiplex real-time PCR assays provide a sensitive, reliable and efficient method to detect Marburg virus and Ebola virus simultaneously.

West Nile encephalitis outbreak in Kerala, India, 2011.

PubMed

Anukumar, B; Sapkal, Gajanan N; Tandale, Babasheb V; Balasubramanian, R; Gangale, Daya

2014-09-01

An outbreak of acute encephalitis syndrome (AES) was reported in Kerala in India in May 2011. The outbreak features were unusual in terms of seasonality, geographical distribution, age group, and clinical manifestations in comparison to the epidemiological features of Japanese Encephalitis. To detect the etiology of the acute encephalitis syndrome outbreak. Investigation of outbreak was undertaken by collection of brief clinical history and epidemiological details along with the specimens for viral diagnosis. The serum/CSF samples (patients=208) received from the sentinel hospitals were subjected to IgM capture ELISA and RT-PCR specific for Japanese encephalitis (JE) virus and West Nile virus (WNV). The JE/WN IgM positive samples were further tested by serum neutralization assay for the presence of JE and WNV specific neutralizing antibody. Most of the affected patients were aged above 15 years. No spatial clustering of the disease was noticed. Cases were observed in premonsoon and early monsoon season and in JE non-endemic area of Kerala. A total of 47 patient samples were positive for in-house JE IgM capture ELISA and WNV IgM capture ELISA. Serum neutralization assay result revealed that 32 of 42 (76.19%) sera were positive for WNV neutralization antibodies. WNV was isolated from a clinical specimen. Phylogenetic analysis of WNV envelope gene revealed 99% homology with Russian Lineage 1 WNV. West Nile virus (WNV) etiology was confirmed by virus isolation and detection of virus specific antibody from clinical specimen. Phylogenetic analysis grouped the current strain in lineage I West Nile virus. Copyright © 2014 Elsevier B.V. All rights reserved.

Phylogeographic analysis of Japanese encephalitis virus in India (1956-2012).

PubMed

Cherian, Sarah S; Walimbe, A M

2015-12-01

Japanese encephalitis virus (JEV) isolates from India phylogenetically belong to two genotypes, III and I. We used envelope gene sequences from GenBank, representing different states of India and other countries, to study the spatiotemporal transmission histories of these two JEV genotypes separately. Genotype III was found to have been successively introduced in the 1930s, 1950s and 1960s, followed by genotype I twice around 2003-2006. Changes in JEV disease patterns in India over the last five decades could thus be attributed to multiple introductions of JEV strains from neighboring Asian countries along with increased transmission potential due to altered ecological settings.

Enterovirus 71 encephalomyelitis and Japanese encephalitis can be distinguished by topographic distribution of inflammation and specific intraneuronal detection of viral antigen and RNA.

PubMed

Wong, K T; Ng, K Y; Ong, K C; Ng, W F; Shankar, S K; Mahadevan, A; Radotra, B; Su, I J; Lau, G; Ling, A E; Chan, K P; Macorelles, P; Vallet, S; Cardosa, M J; Desai, A; Ravi, V; Nagata, N; Shimizu, H; Takasaki, T

2012-08-01

To investigate if two important epidemic viral encephalitis in children, Enterovirus 71 (EV71) encephalomyelitis and Japanese encephalitis (JE) whose clinical and pathological features may be nonspecific and overlapping, could be distinguished. Tissue sections from the central nervous system of infected cases were examined by light microscopy, immunohistochemistry and in situ hybridization. All 13 cases of EV71 encephalomyelitis collected from Asia and France invariably showed stereotyped distribution of inflammation in the spinal cord, brainstem, hypothalamus, cerebellar dentate nucleus and, to a lesser extent, cerebral cortex and meninges. Anterior pons, corpus striatum, thalamus, temporal lobe, hippocampus and cerebellar cortex were always uninflamed. In contrast, the eight JE cases studied showed inflammation involving most neuronal areas of the central nervous system, including the areas that were uninflamed in EV71 encephalomyelitis. Lesions in both infections were nonspecific, consisting of perivascular and parenchymal infiltration by inflammatory cells, oedematous/necrolytic areas, microglial nodules and neuronophagia. Viral inclusions were absent. Immunohistochemistry and in situ hybridization assays were useful to identify the causative virus, localizing viral antigens and RNA, respectively, almost exclusively to neurones. The stereotyped distribution of inflammatory lesions in EV71 encephalomyelitis appears to be very useful to help distinguish it from JE. © 2011 The Authors. Neuropathology and Applied Neurobiology © 2011 British Neuropathological Society.

The Molecular Specificity of the Human Antibody Response to Dengue Virus Infections.

PubMed

Gallichotte, Emily N; Baric, Ralph S; de Silva, Aravinda M

2018-01-01

Dengue viruses (DENV) are mosquito-borne positive sense RNA viruses in the family Flaviviridae. The four serotypes of DENV (DENV1, DENV2, DENV3, DENV4) are widely distributed and it is estimated over a third of the world's population is at risk of infection [4]. While the majority of infections are asymptomatic, DENV infection can cause a spectrum of disease, from mild flu-like symptoms, to the more severe DENV hemorrhagic fever and shock syndrome [24]. Over the past 20 years, there have been intense efforts to develop a tetravalent live-attenuated DENV vaccine [36]. The process of vaccine development has been largely empirical, because effective live attenuated vaccines have been developed for other flaviviruses like yellow fever and Japanese encephalitis viruses. However, recent results from phase III live attenuated DENV vaccine efficacy trials are mixed with evidence for efficacy in some populations but not others [20]. In light of unexpected results from DENV vaccine trials, in this chapter we will review recent discoveries about the human antibody response to natural DENV infection and discuss the relevance of this work to understanding vaccine performance.

Production of Japanese encephalitis virus-like particles in insect cells.

PubMed

Yamaji, Hideki; Konishi, Eiji

2013-01-01

Virus-like particles (VLPs) are composed of one or several recombinant viral surface proteins that spontaneously assemble into particulate structures without the incorporation of virus DNA or RNA. The baculovirus-insect cell system has been used extensively for the production of recombinant virus proteins including VLPs. While the baculovirus-insect cell system directs the transient expression of recombinant proteins in a batch culture, stably transformed insect cells allow constitutive production. In our recent study, a secretory form of Japanese encephalitis (JE) VLPs was successfully produced by Trichoplusia ni BTI-TN-5B1-4 (High Five) cells engineered to coexpress the JE virus (JEV) premembrane (prM) and envelope (E) proteins. A higher yield of E protein was attained with recombinant High Five cells than with the baculovirus-insect cell system. This study demonstrated that recombinant insect cells offer a promising approach to the high-level production of VLPs for use as vaccines and diagnostic antigens.

Antibodies to H5 subtype avian influenza virus and Japanese encephalitis virus in northern pintails (Anas acuta) sampled in Japan

USGS Publications Warehouse

Ramey, Andy M.; Spackman, Erica; Yeh, Jung-Yong; Fujita, Go; Konishi, Kan; Reed, John A.; Wilcox, Benjamin R.; Brown, Justin D.; Stallknecht, David E.

2013-01-01

Blood samples from 105 northern pintails (Anas acuta) captured on Hokkaido, Japan were tested for antibodies to avian influenza virus (AIV), Japanese encephalitis virus (JEV), and West Nile virus (WNV) to assess possible involvement of this species in the spread of economically important and potentially zoonotic pathogens. Antibodies to AIV were detected in 64 of 105 samples (61%). Of the 64 positives, 95% and 81% inhibited agglutination of two different H5 AIV antigens (H5N1 and H5N9), respectively. Antibodies to JEV and WNV were detected in five (5%) and none of the samples, respectively. Results provide evidence for prior exposure of migrating northern pintails to H5 AIV which couldhave implications for viral shedding and disease occurrence. Results also provide evidence for limited involvement of this species in the transmission and spread of flaviviruses during spring migration.

Role of communally nesting ardeid birds in the epidemiology of West Nile virus revisited.

PubMed

Reisen, William K; Wheeler, Sarah; Armijos, M Veronica; Fang, Ying; Garcia, Sandra; Kelley, Kara; Wright, Stan

2009-06-01

Although herons and egrets in the family Ardeidae frequently have been associated with viruses in the Japanese encephalitis virus serocomplex, communal nesting colonies do not appear to be a focus of early season and rapid amplification of West Nile virus (WNV) in California. Evidence for repeated WNV infection was found by testing living and dead nestlings collected under trees with mixed species ardeid colonies nesting above in an oak grove near the University of California arboretum in Davis and in a Eucalyptus grove at a rural farmstead. However, mosquito infection rates at both nesting sites were low and positive pools did not occur earlier than at comparison sites within the City of Davis or at the Yolo Bypass wetlands managed for rice production and waterfowl habitat. Black-crowned night herons (Nycticorax nycticorax) were the most abundant and frequently infected ardeid species, indicating that WNV may be an important cause of mortality among nestlings of this species.

Production of single-round infectious chimeric flaviviruses with DNA-based Japanese encephalitis virus replicon.

PubMed

Suzuki, Ryosuke; Ishikawa, Tomohiro; Konishi, Eiji; Matsuda, Mami; Watashi, Koichi; Aizaki, Hideki; Takasaki, Tomohiko; Wakita, Takaji

2014-01-01

A method for rapid production of single-round infectious particles (SRIPs) of flavivirus would be useful for viral mutagenesis studies. Here, we established a DNA-based production system for SRIPs of flavivirus. We constructed a Japanese encephalitis virus (JEV) subgenomic replicon plasmid, which lacked the C-prM-E (capsid-pre-membrane-envelope) coding region, under the control of the cytomegalovirus promoter. When the JEV replicon plasmid was transiently co-transfected with a JEV C-prM-E expression plasmid into 293T cells, SRIPs were produced, indicating successful trans-complementation with JEV structural proteins. Equivalent production levels were observed when C and prM-E proteins were provided separately. Furthermore, dengue types 1-4, West Nile, yellow fever or tick-borne encephalitis virus prM-E proteins could be utilized for production of chimaeric flavivirus SRIPs, although the production was less efficient for dengue and yellow fever viruses. These results indicated that our plasmid-based system is suitable for investigating the life cycles of flaviviruses, diagnostic applications and development of safer vaccine candidates.

Etiology and prognosis of acute viral encephalitis and meningitis in Chinese children: a multicentre prospective study.

PubMed

Ai, Junhong; Xie, Zhengde; Liu, Gang; Chen, Zongbo; Yang, Yong; Li, Yuning; Chen, Jing; Zheng, Guo; Shen, Kunling

2017-07-14

In China, there were few studies about the pathogens of acute viral encephalitis and meningitis in children in recent years. The aims of this study were to characterize the etiology and prognosis of acute viral encephalitis and meningitis in Chinese children. This was a multicentre prospective study. Two hundred and sixty one viral encephalitis patients and 285 viral meningitis patients were enrolled. The mean age of viral encephalitis and meningitis were 5.88 ± 3.60 years and 6.39 ± 3.57 years, respectively. Real-time reverse transcription PCR and multiplex PCR were used to detect human enteroviruses and herpes viruses in cerebrospinal fluid (CSF) of patients with encephalitis or meningitis. The enzyme-linked immune absorbent assay (ELISA) was used for detecting IgM antibody against Japanese encephalitis virus (JEV) in CSF and against mumps virus, tick-borne encephalitis virus (TBEV), dengue virus and rubella virus in acute serum. The clinical and outcome data were collected during patients' hospitalization. The etiology of viral encephalitis was confirmed in 52.5% patients. The primary pathogen was human enteroviruses (27.7%) in viral encephalitis. The incidence of sequelae and the fatality rate of viral encephalitis with confirmed etiology were 7.5% and 0.8%, respectively. The etiology of viral meningitis was identified in 42.8% cases. The leading pathogen was also human enteroviruses (37.7%) in viral meningitis. The prognosis of viral meningitis was favorable with only 0.7% patients had neurological sequelae. Human enteroviruses were the leading cause both in acute viral encephalitis and viral meningitis in children. The incidence of sequelae and fatality rate of viral encephalitis with confirmed etiology were 7.5% and 0.8%, respectively. The prognosis of viral meningitis was favorable compared to viral encephalitis.

Medically important arboviruses of the United States and Canada.

PubMed Central

Calisher, C H

1994-01-01

Of more than 500 arboviruses recognized worldwide, 5 were first isolated in Canada and 58 were first isolated in the United States. Six of these viruses are human pathogens: western equine encephalitis (WEE) and eastern equine encephalitis (EEE) viruses (family Togaviridae, genus Alphavirus), St. Louis encephalitis (SLE) and Powassan (POW) viruses (Flaviviridae, Flavivirus), LaCrosse (LAC) virus (Bunyaviridae, Bunyavirus), and Colorado tick fever (CTF) virus (Reoviridae, Coltivirus). Their scientific histories, geographic distributions, virology, epidemiology, vectors, vertebrate hosts, transmission, pathogenesis, clinical and differential diagnoses, control, treatment, and laboratory diagnosis are reviewed. In addition, mention is made of the Venezuelan equine encephalitis (VEE) complex viruses (family Togaviridae, genus Alphavirus), which periodically cause human and equine disease in North America. WEE, EEE, and SLE viruses are transmitted by mosquitoes between birds; POW and CTF viruses, between wild mammals by ticks; LAC virus, between small mammals by mosquitoes; and VEE viruses, between small or large mammals by mosquitoes. Human infections are tangential to the natural cycle. Such infections range from rare to focal but are relatively frequent where they occur. Epidemics of WEE, EEE, VEE, and SLE viruses have been recorded at periodic intervals, but prevalence of infections with LAC and CTF viruses typically are constant, related to the degree of exposure to infected vectors. Infections with POW virus appear to be rare. Adequate diagnostic tools are available, but treatment is mainly supportive, and greater efforts at educating the public and the medical community are suggested if infections are to be prevented. PMID:8118792

Tick-Borne Encephalitis Virus Nonstructural Protein NS5 Induces RANTES Expression Dependent on the RNA-Dependent RNA Polymerase Activity.

PubMed

Zheng, Zifeng; Yang, Jieyu; Jiang, Xuan; Liu, Yalan; Zhang, Xiaowei; Li, Mei; Zhang, Mudan; Fu, Ming; Hu, Kai; Wang, Hanzhong; Luo, Min-Hua; Gong, Peng; Hu, Qinxue

2018-05-14

Tick-borne encephalitis virus (TBEV) is one of the flaviviruses that targets the CNS and causes encephalitis in humans. The mechanism of TBEV that causes CNS destruction remains unclear. It has been reported that RANTES-mediated migration of human blood monocytes and T lymphocytes is specifically induced in the brain of mice infected with TBEV, which causes ensuing neuroinflammation and may contribute to brain destruction. However, the viral components responsible for RANTES induction and the underlying mechanisms remain to be fully addressed. In this study, we demonstrate that the NS5, but not other viral proteins of TBEV, induces RANTES production in human glioblastoma cell lines and primary astrocytes. TBEV NS5 appears to activate the IFN regulatory factor 3 (IRF-3) signaling pathway in a manner dependent on RIG-I/MDA5, which leads to the nuclear translocation of IRF-3 to bind with RANTES promoter. Further studies reveal that the activity of RNA-dependent RNA polymerase (RdRP) but not the RNA cap methyltransferase is critical for TBEV NS5-induced RANTES expression, and this is likely due to RdRP-mediated synthesis of dsRNA. Additional data indicate that the residues at K359, D361, and D664 of TBEV NS5 are critical for RdRP activity and RANTES induction. Of note, NS5s from other flaviviruses, including Japanese encephalitis virus, West Nile virus, Zika virus, and dengue virus, can also induce RANTES expression, suggesting the significance of NS5-induced RANTES expression in flavivirus pathogenesis. Our findings provide a foundation for further understanding how flaviviruses cause neuroinflammation and a potential viral target for intervention. Copyright © 2018 by The American Association of Immunologists, Inc.

Coupling of replication and assembly in flaviviruses.

PubMed

Apte-Sengupta, Swapna; Sirohi, Devika; Kuhn, Richard J

2014-12-01

Flaviviruses affect hundreds of millions of people each year causing tremendous morbidity and mortality worldwide. This genus includes significant human pathogens such as dengue, West Nile, yellow fever, tick-borne encephalitis and Japanese encephalitis virus among many others. The disease caused by these viruses can range from febrile illness to hemorrhagic fever and encephalitis. A deeper understanding of the virus life cycle is required to foster development of antivirals and vaccines, which are an urgent need for many flaviviruses, especially dengue. The focus of this review is to summarize our current knowledge of flaviviral replication and assembly, the proteins and lipids involved therein, and how these processes are coordinated for efficient virus production. Copyright © 2014 Elsevier B.V. All rights reserved.

Molecular characterization of two Rocio flavivirus strains isolated during the encephalitis epidemic in São Paulo State, Brazil and the development of a one-step RT-PCR assay for diagnosis.

PubMed

Coimbra, Terezinha Lisieux Moraes; Santos, Raimundo N; Petrella, Selma; Nagasse-Sugahara, Teresa Keico; Castrignano, Silvana Beres; Santos, Cecília L Simões

2008-01-01

Rocio virus (ROCV) was responsible for an explosive encephalitis epidemic in the 1970s affecting about 1,000 residents of 20 coastland counties in São Paulo State, Brazil. ROCV was first isolated in 1975 from the cerebellum of a fatal human case of encephalitis. Clinical manifestations of the illness are similar to those described for St. Louis encephalitis. ROCV shows intense antigenic cross-reactivity with Japanese encephalitis complex (JEC) viruses, particularly with Ilheus (ILHV), St. Louis encephalitis, Murray Valley and West Nile viruses. In this study, we report a specific RT-PCR assay for ROCV diagnosis and the molecular characterization of the SPAn37630 and SPH37623 strains. Partial nucleotide sequences of NS5 and E genes determined from both strains were used in phylogenetic analysis. The results indicated that these strains are closely related to JEC viruses, but forming a distinct subclade together with ILHV, in accordance with results recently reported by Medeiros et al. (2007).

Experimental evidence that RNA recombination occurs in the Japanese encephalitis virus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chuang, C.-K.; Chen, W.-J., E-mail: wjchen@mail.cgu.edu.t; Department of Public Health and Parasitology, Chang Gung University, Kwei-San, Tao-Yuan 33332, Taiwan

2009-11-25

Due to the lack of a proofreading function and error-repairing ability of genomic RNA, accumulated mutations are known to be a force driving viral evolution in the genus Flavivirus, including the Japanese encephalitis (JE) virus. Based on sequencing data, RNA recombination was recently postulated to be another factor associated with genomic variations in these viruses. We herein provide experimental evidence to demonstrate the occurrence of RNA recombination in the JE virus using two local pure clones (T1P1-S1 and CJN-S1) respectively derived from the local strains, T1P1 and CJN. Based on results from a restriction fragment length polymorphism (RFLP) assay onmore » the C/preM junction comprising a fragment of 868 nucleotides (nt 10-877), the recombinant progeny virus was primarily formed in BHK-21 cells that had been co-infected with the two clones used in this study. Nine of 20 recombinant forms of the JE virus had a crossover in the nt 123-323 region. Sequencing data derived from these recombinants revealed that no nucleotide deletion or insertion occurred in this region favoring crossovers, indicating that precisely, not aberrantly, homologous recombination was involved. With site-directed mutagenesis, three stem-loop secondary structures were destabilized and re-stabilized in sequence, leading to changes in the frequency of recombination. This suggests that the conformation, not the free energy, of the secondary structure is important in modulating RNA recombination of the virus. It was concluded that because RNA recombination generates genetic diversity in the JE virus, this must be considered particularly in studies of viral evolution, epidemiology, and possible vaccine safety.« less

Seasonal Patterns of Japanese Encephalitis and Associated Meteorological Factors in Taiwan.

PubMed

Lin, Che-Liang; Chang, Hsiao-Ling; Lin, Chuan-Yao; Chen, Kow-Tong

2017-10-29

The persistent transmission of Japanese encephalitis virus (JEV) in Taiwan necessitates exploring the risk factors of occurrence of Japanese encephalitis (JE). The purpose of this study was to assess the relationship between meteorological factors and the incidence of JE in Taiwan. We collected data for cases of JE reported to the Taiwan Centers for Disease Control (Taiwan CDC) from 2000 to 2014. Meteorological data were obtained from the Taiwan Central Weather Bureau. The relationships between weather variability and the incidence of JE in Taiwan were determined via Poisson regression analysis and a case-crossover methodology. During the 15-year study period, a total of 379 cases of JE were reported. The incidence of JE showed significant seasonality, with the majority of cases occurring in summertime (for oscillation, p < 0.001). The number of JE cases started to increase at temperatures of 22 °C (r² = 0.88, p < 0.001). Similarly, the number of JE cases began to increase at a relative humidity of 70-74% (r² = 0.75, p < 0.005). The number of JE cases was positively associated with mean temperature and relative humidity in the period preceding the infection. In conclusion, the occurrence of JE is significantly associated with increasing temperature and relative humidity in Taiwan. Therefore, these factors could be regarded as warning signals indicating the need to implement preventive measures.

Mutation of I176R in the E coding region weakens Japanese encephalitis virus neurovirulence, but not its growth rate in BHK-21 cells.

PubMed

Zhou, Yuyong; Wu, Rui; Zhao, Qin; Chang, Yung-Fu; Wen, Xintian; Feng, Yao; Huang, Xiaobo; Wen, Yiping; Yan, Qigui; Huang, Yong; Ma, Xiaoping; Han, Xinfeng; Cao, Sanjie

2018-05-01

Previously, we isolated the Japanese encephalitis virus (JEV) strain SCYA201201. In this study, we passed the SCYA201201 strain in Syrian baby hamster kidney (BHK-21) cells 120 times to obtain the SCYA201201-0901 strain, which exhibited an attenuated phenotype in mice. Comparison of SCYA201201-0901 amino acid sequences with those of other JEV strains revealed a single mutation, I176R, in the E coding region. Using reverse genetic technology, we provide evidence that this single E-I176R mutation does not affect virus growth in BHK-21 cells but significantly decreases JEV neurovirulence in mice. This study provides critical information for understanding the molecular mechanism of JEV attenuation.

A Population-Based Acute Meningitis and Encephalitis Syndromes Surveillance in Guangxi, China, May 2007- June 2012

PubMed Central

Chongsuvivatwong, Virasakdi; Wu, Xinghua; Bi, Fuyin; Hadler, Stephen C.; Jiraphongsa, Chuleeporn; Sornsrivichai, Vorasith; Lin, Mei; Quan, Yi

2015-01-01

Objectives Acute meningitis and encephalitis (AME) are common diseases with the main pathogens being viruses and bacteria. As specific treatments are different, it is important to develop clinical prediction rules to distinguish aseptic from bacterial or fungal infection. In this study we evaluated the incidence rates, seasonal variety and the main etiologic agents of AME, and identified factors that could be used to predict the etiologic agents. Methods A population-based AME syndrome surveillance system was set up in Guigang City, Guangxi, involving 12 hospitals serving the study communities. All patients meeting the case definition were investigated. Blood and/or cerebrospinal fluid were tested for bacterial pathogens using culture or RT-PCR and serological tests for viruses using enzyme-linked immunosorbent assays. Laboratory testing variables were grouped using factor analysis. Multinomial logistic regression was used to predict the etiology of AME. Results From May 2007 to June 2012, the annual incidence rate of AME syndrome, and disease specifically caused by Japanese encephalitis (JE), other viruses, bacteria and fungi were 12.55, 0.58, 4.57, 0.45 and 0.14 per 100,000 population, respectively. The top three identified viral etiologic agents were enterovirus, mumps virus, and JE virus, and for bacteria/fungi were Streptococcus sp., Cryptococcus neoformans and Staphylococcus sp. The incidence of JE and other viruses affected younger populations and peaked from April to August. Alteration of consciousness and leukocytosis were more likely to be caused by JE, bacteria and fungi whereas CSF inflammation was associated with bacterial/fungal infection. Conclusions With limited predictive validity of symptoms and signs and routine laboratory tests, specific tests for JE virus, mumps virus and enteroviruses are required to evaluate the immunization impact and plan for further intervention. CSF bacterial culture cannot be omitted in guiding clinical decisions regarding patient treatment. PMID:26633824

Sertoli Cells Are Susceptible to ZIKV Infection in Mouse Testis.

PubMed

Sheng, Zi-Yang; Gao, Na; Wang, Zhao-Yang; Cui, Xiao-Yun; Zhou, De-Shan; Fan, Dong-Ying; Chen, Hui; Wang, Pei-Gang; An, Jing

2017-01-01

Flaviviruses including Dengue virus (DENV), Yellow fever virus (YFV), West Nile virus (WNV), and Japanese encephalitis virus (JEV) are global health problems that caused several serious diseases such as fever, hemorrhagic fever, and encephalitis in the past century. Recently, Zika virus (ZIKV) which spreads from Asia to American and causes millions of infections emerges as a new dangerous member of the genus of Flavivirus . Unlike other well-known flaviviruses, ZIKV can be transmitted sexually and infect testes in murine models. Its impacts on sperm functions, and the exact susceptible cells, however, are not entirely clear. To investigate these issues, we infected interferon α/β and γ receptors deficient AG6 mice with ZIKV and examined the outcomes of infection using an assortment of physiological, histopathological, immunological, and virological techniques. We found that infected mice displayed signs of reproductive system disorder, altered androgen levels in serum, and high viral load in semen and testes. Additionally, histopathological examinations revealed marked atrophy of seminiferous tubules and significant reduction in lumen size. Notably, these were accompanied by positive staining of ZIKV antigens on sertoli cells, detection of viral particles and vacuole changes within cytoplasm of sertoli cells. The susceptibility of sertoli cells to ZIKV was further validated in vitro study using cell lines. Importantly, the disruption of tight junctions within testis and altered sperm morphology were also observed in ZIKV infected mice. It is well-known that tight junctions formed by adjacent sertoli cells are major component of blood testis barrier, which plays important roles in maintenance of microenvironment for spermagenesis in testis. Taken together, these results demonstrate that sertoli cells are susceptible to ZIKV infection, which results in the disruption of tight junctions in testis and causes abnormal spermatogenesis in mice. These results also imply that long-term impact of ZIKV infection on human male reproductive system requires close monitoring.

Experimental encephalitis in monkeys caused by the Powassan virus.

PubMed

Frolova, M P; Isachkova, L M; Shestopalova, N M; Pogodina, V V

1985-01-01

We have carried out a comparative study of the experimental infection of monkeys with the P-40 strain of the Powassen virus, isolated in the Primor'e Territory of the USSR, and with the Canadian prototype LB strain. The Powassan virus was found to be pathogenic for Macaca rhesus. The clinical and pathomorphological picture of the experimental encephalitis was studied, and the full identity of the infection produced in the monkeys by the P-40 strain and the Canadian LB strain of the Powassan virus was demonstrated. On electron microscopic examination of the central nervous system the virus was detected in the neurons, glial cells, and intercellular spaces. The virions of the strains studied have identical morphological parameters, being 37-45 nm in diameter and of spherical shape. The data obtained indicated a marked neurotropism of the virus. They will contribute to the elucidation of the role of the virus in the infection pathology of humans, i.e., in the differentiation of encephalitis cases not associated etiologically with the virus of the spring-summer tickborne encephalitis.

Neuro-Immune Mechanisms in Response to Venezuelan equine encephalitis Virus Infection

DTIC Science & Technology

2000-05-01

horses . They were subsequently shown to be previously unrecognized viral agents of severe equine encephalitis (Smith et al., 1997). One member of...iii ABSTRACT NEURO-IMMUNE MECHANISMS IN RESPONSE TO VENEZUELAN EQUINE ENCEPHALITIS VIRUS INFECTION Major Bruce A. Schoneboom directed by Franziska B...Grieder, DVM, Ph.D., Assistant Professor of Microbiology and Immunology, Molecular and Cellular Biology, and Neuroscience Venezuelan equine

Vaccine adverse events reported in post-marketing study of the Kitasato Institute from 1994 to 2004.

PubMed

Nakayama, Tetsuo; Onoda, Kazumasa

2007-01-05

General physicians, pediatricians and parents realize that serious adverse events occur with an extremely rare incidence, but have no information on the incidences of vaccine-associated adverse events. A proper understanding of vaccine adverse events would be helpful in promoting an immunization strategy. Causal association can rarely be determined in adverse events through laboratory examinations. We examined the cases reported in the post-marketing surveillance of the Kitasato Institute, categorizing them into two groups: allergic reactions and severe systemic illnesses. Anaphylactic patients with gelatin allergy after immunization with live measles, rubella and mumps monovalent vaccines have been reported since 1993, but the number of reported cases with anaphylaxis dramatically decreased after 1999 when gelatin was removed from all brands of DPT. The incidence of anaphylactic reaction was estimated to be 0.63 per million for Japanese encephalitis virus (JEV) vaccine, 0.95 for DPT and 0.68 for Influenza vaccine, but the causative component has not yet been specified. Among 67.2 million immunization practices, 6 cases with encephalitis or encephalopathy, 7 with acute disseminated encephalomyelitis (ADEM), 10 with Guillain-Barré syndrome and 12 with idiopathic thrombocytopenic purpura (ITP) were reported. The wild-type measles virus genome was detected in a patient with encephalitis and in two of four bone marrow aspirates obtained from ITP after measles vaccination. Enterovirus infection was identified in two patients after mumps vaccination (one each with encephalitis and ADEM), one patient with encephalitis after immunization with JEV vaccine, and one with aseptic meningitis after immunization with influenza vaccine. The total estimated incidence of serious neurological illness after vaccination was 0.1-0.2 per million immunization practices. We found that enterovirus or wild-type measles virus infection was coincidentally associated with vaccination in several cases suspected of being vaccine adverse events.

Ablation of CD11c(hi) dendritic cells exacerbates Japanese encephalitis by regulating blood-brain barrier permeability and altering tight junction/adhesion molecules.

PubMed

Kim, Jin Hyoung; Hossain, Ferdaus Mohd Altaf; Patil, Ajit Mahadev; Choi, Jin Young; Kim, Seong Bum; Uyangaa, Erdenebelig; Park, Sang-Youel; Lee, John-Hwa; Kim, Bumseok; Kim, Koanhoi; Eo, Seong Kug

2016-10-01

Japanese encephalitis (JE), characterized by extensive neuroinflammation following infection with neurotropic JE virus (JEV), is becoming a leading cause of viral encephalitis due to rapid changes in climate and demography. The blood-brain barrier (BBB) plays an important role in restricting neuroinvasion of peripheral leukocytes and virus, thereby regulating the progression of viral encephalitis. In this study, we explored the role of CD11c(hi) dendritic cells (DCs) in regulating BBB integrity and JE progression using a conditional depletion model of CD11c(hi) DCs. Transient ablation of CD11c(hi) DCs resulted in markedly increased susceptibility to JE progression along with highly increased neuro-invasion of JEV. In addition, exacerbated JE progression in CD11c(hi) DC-ablated hosts was closely associated with increased expression of proinflammatory cytokines (IFN-β, IL-6, and TNF-α) and CC chemokines (CCL2, CCL3, CXCL2) in the brain. Moreover, our results revealed that the exacerbation of JE progression in CD11c(hi) DC-ablated hosts was correlated with enhanced BBB permeability and reduced expression of tight junction and adhesion molecules (claudin-5, ZO-1, occluding, JAMs). Ultimately, our data conclude that the ablation of CD11c(hi) DCs provided a subsidiary impact on BBB integrity and the expression of tight junction/adhesion molecules, thereby leading to exacerbated JE progression. These findings provide insight into the secondary role of CD11c(hi) DCs in JE progression through regulation of BBB integrity and the expression of tight junction/adhesion molecules. Copyright © 2016 Elsevier Ltd. All rights reserved.

Powassan virus encephalitis, Minnesota, USA.

PubMed

Birge, Justin; Sonnesyn, Steven

2012-10-01

Powassan virus (POWV) is a rare tick-borne agent of encephalitis in North America. Historically, confirmed cases occurred mainly in the northeastern United States. Since 2008, confirmed cases in Minnesota and Wisconsin have increased. We report a fatal case of POWV encephalitis in Minnesota. POWV infection should be suspected in tick-exposed patients with viral encephalitis.

Powassan Virus Encephalitis, Minnesota, USA

PubMed Central

Sonnesyn, Steven

2012-01-01

Powassan virus (POWV) is a rare tick-borne agent of encephalitis in North America. Historically, confirmed cases occurred mainly in the northeastern United States. Since 2008, confirmed cases in Minnesota and Wisconsin have increased. We report a fatal case of POWV encephalitis in Minnesota. POWV infection should be suspected in tick-exposed patients with viral encephalitis. PMID:23017222

Flavivirus NS1 protein in infected host sera enhances viral acquisition by mosquitoes.

PubMed

Liu, Jianying; Liu, Yang; Nie, Kaixiao; Du, Senyan; Qiu, Jingjun; Pang, Xiaojing; Wang, Penghua; Cheng, Gong

2016-06-20

The arbovirus life cycle involves viral transfer between a vertebrate host and an arthropod vector, and acquisition of virus from an infected mammalian host by a vector is an essential step in this process. Here, we report that flavivirus nonstructural protein-1 (NS1), which is abundantly secreted into the serum of an infected host, plays a critical role in flavivirus acquisition by mosquitoes. The presence of dengue virus (DENV) and Japanese encephalitis virus NS1s in the blood of infected interferon-α and γ receptor-deficient mice (AG6) facilitated virus acquisition by their native mosquito vectors because the protein enabled the virus to overcome the immune barrier of the mosquito midgut. Active immunization of AG6 mice with a modified DENV NS1 reduced DENV acquisition by mosquitoes and protected mice against a lethal DENV challenge, suggesting that immunization with NS1 could reduce the number of virus-carrying mosquitoes as well as the incidence of flaviviral diseases. Our study demonstrates that flaviviruses utilize NS1 proteins produced during their vertebrate phases to enhance their acquisition by vectors, which might be a result of flavivirus evolution to adapt to multiple host environments.

Flavivirus NS1 protein in infected host sera enhances viral acquisition by mosquitoes

PubMed Central

Liu, Jianying; Liu, Yang; Nie, Kaixiao; Du, Senyan; Qiu, Jingjun; Pang, Xiaojing; Wang, Penghua; Cheng, Gong

2016-01-01

Summary The arbovirus life cycle involves viral transfer between a vertebrate host and an arthropod vector, and acquisition of virus from an infected mammalian host by a vector is an essential step in this process. Here, we report that flavivirus nonstructural protein-1 (NS1), which is abundantly secreted into the serum of an infected host, plays a critical role in flavivirus acquisition by mosquitoes. The presence of dengue virus (DENV) and Japanese encephalitis virus (JEV) NS1s in the blood of infected interferon alpha and gamma receptor-deficient mice (AG6) facilitated virus acquisition by their native mosquito vectors because the protein enabled the virus to overcome the immune barrier of the mosquito midgut. Active immunization of AG6 mice with a modified DENV NS1 reduced DENV acquisition by mosquitoes and protected mice against a lethal DENV challenge, suggesting that immunization with NS1 could reduce the number of virus-carrying mosquitoes as well as the incidence of flaviviral diseases. Our study demonstrates that flaviviruses utilize NS1 proteins produced during their vertebrate phases to enhance their acquisition by vectors, which might be a result of flavivirus evolution to adapt to multiple host environments. PMID:27562253

Expectoration of Flaviviruses during sugar feeding by mosquitoes (Diptera: Culicidae).

PubMed

van den Hurk, Andrew F; Johnson, Petrina H; Hall-Mendelin, Sonja; Northill, Judy A; Simmons, Russell J; Jansen, Cassie C; Frances, Stephen P; Smith, Greg A; Ritchie, Scott A

2007-09-01

Biological transmission of arboviruses to a vertebrate host occurs when virions are expelled along with saliva during blood feeding by a hematophagous arthropod. We undertook experiments to determine whether mosquitoes expectorate flaviviruses in their saliva while sugar feeding. Batches of Culex annulirostris Skuse and Culex gelidus Theobald (Diptera: Culicidae) were orally infected with Japanese encephalitis (family Flaviviridae, genus Flavivirus, JEV), Kunjin (family Flaviviridae, genus Flavivirus, KUNV; a subtype of West Nile virus), and Murray Valley encephalitis (family Flaviviridae, genus Flavivirus, MVEV) viruses. After a 7-d extrinsic incubation, these mosquitoes were offered sucrose meals via cotton pledgets, which were removed daily and processed for viral RNA by using real-time TaqMan reverse transcriptase-polymerase chain reaction (RT-PCR) assays. JEV, MVEV, and KUNV RNA was detected in all pledgets removed from batches of Cx. gelidus on days 7-14 postexposure. In contrast, detection rates were variable for Cx. annulirostris, with KUNV detected in 0.3 M sucrose pledgets on all days postexposure, and JEV and MVEV detected on 57 and 50% of days postexposure, respectively. Higher concentrations of sucrose in the pledget did not increase virus detection rates. When individual JEV-infected Cx. gelidus were exposed to the sucrose pledget, 73% of mosquitoes expectorated virus with titers that were detectable by TaqMan RT-PCR. These results clearly show that flaviviruses are expectorated by infected mosquitoes during the process of sugar feeding on artificial pledgets. Potential applications of the method for arboviral bioassays and field surveillance are discussed.

A novel immunochromatographic test applied to a serological survey of Japanese encephalitis virus on pig farms in Korea.

PubMed

Cha, Go-Woon; Lee, Eun Ju; Lim, Eun-Joo; Sin, Kang Suk; Park, Woo Won; Jeon, Doo Young; Han, Myung Guk; Lee, Won-Ja; Choi, Woo-Young; Jeong, Young Eui

2015-01-01

Among vertebrate species, pigs are a major amplifying host of Japanese encephalitis virus (JEV) and measuring their seroconversion is a reliable indicator of virus activity. Traditionally, the hemagglutination inhibition test has been used for serological testing in pigs; however, it has several limitations and, thus, a more efficient and reliable replacement test is required. In this study, we developed a new immunochromatographic test for detecting antibodies to JEV in pig serum within 15 min. Specifically, the domain III region of the JEV envelope protein was successfully expressed in soluble form and used for developing the immunochromatographic test. The test was then applied to the surveillance of Japanese encephalitis (JE) in Korea. We found that our immunochromatographic test had good sensitivity (84.8%) and specificity (97.7%) when compared with an immunofluorescence assay used as a reference test. During the surveillance of JE in Korea in 2012, the new immunochromatographic test was used to test the sera of 1,926 slaughtered pigs from eight provinces, and 228 pigs (11.8%) were found to be JEV-positive. Based on these results, we also produced an activity map of JEV, which marked the locations of pig farms in Korea that tested positive for the virus. Thus, the immunochromatographic test reported here provides a convenient and effective tool for real-time monitoring of JEV activity in pigs.

A Novel Immunochromatographic Test Applied to a Serological Survey of Japanese Encephalitis Virus on Pig Farms in Korea

PubMed Central

Cha, Go-Woon; Lee, Eun Ju; Lim, Eun-Joo; Sin, Kang Suk; Park, Woo Won; Jeon, Doo Young; Han, Myung Guk; Lee, Won-Ja; Choi, Woo-Young; Jeong, Young Eui

2015-01-01

Among vertebrate species, pigs are a major amplifying host of Japanese encephalitis virus (JEV) and measuring their seroconversion is a reliable indicator of virus activity. Traditionally, the hemagglutination inhibition test has been used for serological testing in pigs; however, it has several limitations and, thus, a more efficient and reliable replacement test is required. In this study, we developed a new immunochromatographic test for detecting antibodies to JEV in pig serum within 15 min. Specifically, the domain III region of the JEV envelope protein was successfully expressed in soluble form and used for developing the immunochromatographic test. The test was then applied to the surveillance of Japanese encephalitis (JE) in Korea. We found that our immunochromatographic test had good sensitivity (84.8%) and specificity (97.7%) when compared with an immunofluorescence assay used as a reference test. During the surveillance of JE in Korea in 2012, the new immunochromatographic test was used to test the sera of 1,926 slaughtered pigs from eight provinces, and 228 pigs (11.8%) were found to be JEV-positive. Based on these results, we also produced an activity map of JEV, which marked the locations of pig farms in Korea that tested positive for the virus. Thus, the immunochromatographic test reported here provides a convenient and effective tool for real-time monitoring of JEV activity in pigs. PMID:25992769

Safety and immunogenicity of a live attenuated Japanese encephalitis chimeric virus vaccine (IMOJEV®) in children.

PubMed

Chokephaibulkit, K; Houillon, G; Feroldi, E; Bouckenooghe, A

2016-01-01

JE-CV (IMOJEV®, Sanofi Pasteur, France) is a live attenuated virus vaccine constructed by inserting coding sequences of the prM and E structural proteins of the Japanese encephalitis SA14-14-2 virus into the genome of yellow fever 17D virus. Primary immunization with JE-CV requires a single dose of the vaccine. This article reviews clinical trials of JE-CV in children aged up to 6 years conducted in countries across South-East Asia. Strong and persistent antibody responses were observed after single primary and booster doses, with 97% of children seroprotected up to five years after booster vaccination. Models of long-term antibody persistence predict a median duration of protection of approximately 30 years after a booster dose. The safety and reactogenicity profiles of JE-CV primary and booster doses are comparable to other widely used childhood vaccines.

[Usutu virus: a novel flavivirus in Croatia].

PubMed

Vilibić-Čavlek, Tatjana; Barbić Ljubo; Stevanović, Vladimir; Mlinarić-Galinović, Gordana

2015-01-01

Usutu virus (USUV) belongs to the family Flaviviridae, genus Flavivirus, Japanese encephalitis serocomplex. The virus was discovered in 1959 in South Africa and has emerged since 1996 causing epizootics with high avian mortality in Europe. The importance of USUV in humans is not fully understood. However, several human clinical cases of USUV infection described so far indicate the role of this virus as an antropozoonotic agent. In Croatia, serologic evidence of USUV was first documented in 2011 in two horses from Zagreb and Sisak-Moslavina County. In 2012, USUV neutralizing antibodies were found in one human sample from a resident of a Vukovar-Srijem County. Human clinical cases of USUV infection were detected for the first time during the West Nile virus outbreak from July to September 2013. Three patients with USUV neuroinvasive disease were detected in the City of Zagreb and Zagreb County. Our results indicate USUV circulation in Croatia. Further human cases could be expected in the next transmission seasons.

Defining Hsp70 Subnetworks in Dengue Virus Replication Reveals Key Vulnerability in Flavivirus Infection.

PubMed

Taguwa, Shuhei; Maringer, Kevin; Li, Xiaokai; Bernal-Rubio, Dabeiba; Rauch, Jennifer N; Gestwicki, Jason E; Andino, Raul; Fernandez-Sesma, Ana; Frydman, Judith

2015-11-19

Viral protein homeostasis depends entirely on the machinery of the infected cell. Accordingly, viruses can illuminate the interplay between cellular proteostasis components and their distinct substrates. Here, we define how the Hsp70 chaperone network mediates the dengue virus life cycle. Cytosolic Hsp70 isoforms are required at distinct steps of the viral cycle, including entry, RNA replication, and virion biogenesis. Hsp70 function at each step is specified by nine distinct DNAJ cofactors. Of these, DnaJB11 relocalizes to virus-induced replication complexes to promote RNA synthesis, while DnaJB6 associates with capsid protein and facilitates virion biogenesis. Importantly, an allosteric Hsp70 inhibitor, JG40, potently blocks infection of different dengue serotypes in human primary blood cells without eliciting viral resistance or exerting toxicity to the host cells. JG40 also blocks replication of other medically-important flaviviruses including yellow fever, West Nile and Japanese encephalitis viruses. Thus, targeting host Hsp70 subnetworks provides a path for broad-spectrum antivirals. Copyright © 2015 Elsevier Inc. All rights reserved.

Nipah encephalitis - an update.

PubMed

Sherrini, B A; Chong, T T

2014-08-01

Between September 1998 to May 1999, Malaysia and Singapore were hit by an outbreak of fatal encephalitis caused by a novel virus from the paramyxovirus family. This virus was subsequently named as Nipah virus, after the Sungei Nipah village in Negeri Sembilan, where the virus was first isolated. The means of transmission was thought to be from bats-topigs and subsequently pigs-to-human. Since 2001, almost yearly outbreak of Nipah encephalitis has been reported from Bangladesh and West Bengal, India. These outbreaks were characterized by direct bats-to-human, and human-to-human spread of infection. Nipah virus shares many similar characteristics to Hendra virus, first isolated in an outbreak of respiratory illness involving horses in Australia in 1994. Because of their homology, a new genus called Henipavirus (Hendra + Nipah) was introduced. Henipavirus infection is a human disease manifesting most often as acute encephalitis (which may be relapsing or late-onset) or pneumonia, with a high mortality rate. Pteropus bats act as reservoir for the virus, which subsequently lead to human spread. Transmission may be from consumption of food contaminated by bats secretion, contact with infected animals, or human-to-human spread. With wide geographical distribution of Pteropus bats, Henipavirus infection has become an important emerging human infection with worldwide implication.

Cloning and expression of an envelope gene of West Nile virus and evaluation of the protein for use in an IgM ELISA.

PubMed

Saxena, Divyasha; Parida, Manmohan; Rao, Putcha Venkata L; Kumar, Jyoti S

2013-04-01

West Nile virus (WNV) is a neurotropic flavivirus that has emerged globally as a significant cause of viral encephalitis. The early confirmatory diagnosis of WNV infections is important for timely clinical management and epidemiologic control in areas where multiple flaviviruses are endemic. The coexistence of WNV along with other members of flaviviruses like dengue and Japanese encephalitis in India has complicated the serodiagnosis due to cross-reactive antigens. In the present study, the development and evaluation of a highly sensitive and specific IgM enzyme-linked immunosorbent assay (ELISA) using the recombinant envelope protein (rWNV-Env) for rapid, early, and accurate diagnosis of WNV are reported. The gene coding for the envelope protein of WNV was cloned and expressed in pET 28a vector followed by purification of recombinant protein by affinity chromatography. An indirect IgM microplate ELISA using purified rWNV-Env protein was optimized having no cross reactivity with healthy human serum. Furthermore, the specificity of this assay was confirmed by cross checking with serum samples obtained from patients with dengue and Japanese encephalitis viruses. The comparative evaluation of this rWNV-Env protein-specific IgM ELISA with plaque reduction neutralization test assay using 105 acute phase of clinical samples revealed 95% concordance with sensitivity and specificity of 92% and 97%, respectively. The positive and negative predictive values of recombinant-based Env ELISA were 94% and 96%, respectively. The recombinant envelope protein-based WNV-specific ELISA reported in this study will be useful for rapid screening of large numbers of clinical samples in endemic areas during outbreaks. Copyright © 2013 Elsevier Inc. All rights reserved.

Zika virus: a new arboviral public health problem.

PubMed

Demir, Tulin; Kilic, Selcuk

2016-11-01

Zika virus (ZIKV) is a single-stranded RNA virus in the Flaviviridae family and transmitted to human through infected mosquitos (Aedes aegypti and Aedes albopictus). Virus is closely related with other flaviviruses; dengue virus, yellow fever virus, West Nile virus, and Japanese encephalitis virus phylogenetically. Due to the possible relationship between virus and clinical features including microcephaly, ventricule, and eye deformities, Guillain-Barre syndrome increases the interest on this virus gradually. Along with the vector-borne transmission, exposure via blood transfusion and sexual contact are further concerns. Since December 2015, CDC reported 440.000-1.300.000 possible cases in Brazil and as of 19 January 2016, El Salvador, Venezuela, Colombia, Brazil, Surinam, French Guana, Honduras, Mexico, and Panama are the countries with active epidemic. CDC recommends ZIKV screening for all pregnants including asymptomatic cases those living in the active epidemic areas. Recently, virus is detected in the USA and most European countries including UK, Netherlands, Denmark, Switzerland, and Italy as a travel-associated infection. Owing to the changing world with increased capabilities for transportation globally, this vector-borne infection represents a valuable marker for the ability of spreading of any infection from its original area that it was first seen. In this review, we summarized the up-to-date data and reports in terms of the importance of the ZIKV infection in the public health.

Nonstructural protein 1 antibody-based epitope-blocking enzyme-linked immunosorbent assay to differentiate Japanese encephalitis virus from dengue virus infections in humans.

PubMed

Konishi, Eiji; Konishi, Mayu

2011-01-01

Japanese encephalitis virus (JEV) and the four dengue viruses (DENV1-4) are co-distributed in Southeast and South Asia. Since JEV is antigenically cross-reactive with DENV1-4, the differentiation between these viruses using antibody assays may be difficult. Herein, we describe the development of an epitope-blocking enzyme-linked immunosorbent assay (ELISA) using a monoclonal antibody specific for the nonstructural protein 1 (NS1) of JEV (JEV-NS1) to differentiate antibodies against JEV from those against DENV1-4. Hyperimmune mouse sera against JEV-NS1 showed >60% inhibition, whereas those against NS1 of DENV1-4 showed <30% inhibition. The present assay could therefore detect antibodies specific for JEV. For testing of human sera, a temporary cutoff value (30.8%) was calculated the average and standard deviation obtained for sera of control humans negative for JEV antibodies. Human sera positive for antibodies to any of DENV1-4 NS1 but negative for antibodies to JEV-NS1 showed a lower percentage inhibition than the cutoff value. On the other hand, sera with JEV-NS1 antibody levels of ≥0.400, as determined by the conventional ELISA (medially/strongly positive for JEV-NS1 antibodies), showed percentage inhibition greater than the cutoff. Although this blocking ELISA afforded false-negative results for most sera that were weakly positive for JEV-NS1 antibodies, it may be useful for investigating the seroepidemiology of JEV antibodies in dengue-endemic areas.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhao, Baoyu; Yi, Guanghui; Du, Fenglei

The recent outbreak of Zika virus (ZIKV) has infected over 1 million people in over 30 countries. ZIKV replicates its RNA genome using virally encoded replication proteins. Nonstructural protein 5 (NS5) contains a methyltransferase for RNA capping and a polymerase for viral RNA synthesis. Here we report the crystal structures of full-length NS5 and its polymerase domain at 3.0 Å resolution. The NS5 structure has striking similarities to the NS5 protein of the related Japanese encephalitis virus. The methyltransferase contains in-line pockets for substrate binding and the active site. Key residues in the polymerase are located in similar positions tomore » those of the initiation complex for the hepatitis C virus polymerase. The polymerase conformation is affected by the methyltransferase, which enables a more efficiently elongation of RNA synthesis in vitro. Altogether, our results will contribute to future studies on ZIKV infection and the development of inhibitors of ZIKV replication.« less

Molecular phylogenetic and evolutionary analyses of Muar strain of Japanese encephalitis virus reveal it is the missing fifth genotype.

PubMed

Mohammed, Manal A F; Galbraith, Sareen E; Radford, Alan D; Dove, Winifred; Takasaki, Tomohiko; Kurane, Ichiro; Solomon, Tom

2011-07-01

Japanese encephalitis virus (JEV) is the most important cause of epidemic encephalitis worldwide but its origin is unknown. Epidemics of encephalitis suggestive of Japanese encephalitis (JE) were described in Japan from the 1870s onwards. Four genotypes of JEV have been characterised and representatives of each genotype have been fully sequenced. Based on limited information, a single isolate from Malaysia is thought to represent a putative fifth genotype. We have determined the complete nucleotide and amino acid sequence of Muar strain and compared it with other fully sequenced JEV genomes. Muar was the least similar, with nucleotide divergence ranging from 20.2 to 21.2% and amino acid divergence ranging from 8.5 to 9.9%. Phylogenetic analysis of Muar strain revealed that it does represent a distinct fifth genotype of JEV. We elucidated Muar signature amino acids in the envelope (E) protein, including E327 Glu on the exposed lateral surface of the putative receptor binding domain which distinguishes Muar strain from the other four genotypes. Evolutionary analysis of full-length JEV genomes revealed that the mean evolutionary rate is 4.35 × 10(-4) (3.4906 × 10(-4) to 5.303 × 10(-4)) nucleotides substitutions per site per year and suggests JEV originated from its ancestral virus in the mid 1500s in the Indonesia-Malaysia region and evolved there into different genotypes, which then spread across Asia. No strong evidence for positive selection was found between JEV strains of the five genotypes and the E gene has generally been subjected to strong purifying selection. Copyright © 2011 Elsevier B.V. All rights reserved.

Interim Report on SNP analysis and forensic microarray probe design for South American hemorrhagic fever viruses, tick-borne encephalitis virus, henipaviruses, Old World Arenaviruses, filoviruses, Crimean-Congo hemorrhagic fever viruses, Rift Valley fever

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jaing, C; Gardner, S

The goal of this project is to develop forensic genotyping assays for select agent viruses, enhancing the current capabilities for the viral bioforensics and law enforcement community. We used a multipronged approach combining bioinformatics analysis, PCR-enriched samples, microarrays and TaqMan assays to develop high resolution and cost effective genotyping methods for strain level forensic discrimination of viruses. We have leveraged substantial experience and efficiency gained through year 1 on software development, SNP discovery, TaqMan signature design and phylogenetic signature mapping to scale up the development of forensics signatures in year 2. In this report, we have summarized the whole genomemore » wide SNP analysis and microarray probe design for forensics characterization of South American hemorrhagic fever viruses, tick-borne encephalitis viruses and henipaviruses, Old World Arenaviruses, filoviruses, Crimean-Congo hemorrhagic fever virus, Rift Valley fever virus and Japanese encephalitis virus.« less

[Mono- and mixed infection by the tick-borne encephalitis and Powassan viruses of tissue explants from ticks of the genus Hyalomma].

PubMed

Chunikhin, S P; Khozinskaia, G A; Stefutkina, L F; Korolev, M B

1984-01-01

The paper presents results of virusological and electron microscope studies of the reproduction of viruses of tick-borne encephalitis and Povassan at mono- and mixed persistent infection of explants of imaginal tissues of Hyalomma anatolicum and H. dromedarii with these viruses. The virus reproduction in explants was observed within 208 to 217 days after the infection. Joint reproduction of two model viruses within 1-2 months after the infection can take place and after that the inhibition of the reproduction of one of the viruses. This inhibition can be of cyclic character.

Emerging Causes of Arbovirus Encephalitis in North America: Powassan, Chikungunya, and Zika Viruses.

PubMed

Doughty, Christopher T; Yawetz, Sigal; Lyons, Jennifer

2017-02-01

Arboviruses are arthropod-borne viruses transmitted by the bite of mosquitoes, ticks, or other arthropods. Arboviruses are a common and an increasing cause of human illness in North America. Powassan virus, Chikungunya virus, and Zika virus are arboviruses that have all recently emerged as increasing causes of neurologic illness. Powassan virus almost exclusively causes encephalitis, but cases are rare, sporadic, and restricted to portions of North America and Russia. Chikungunya virus has spread widely across the world, causing millions of infections. Encephalitis is a rare manifestation of illness but is more common and severe in neonates and older adults. Zika virus has recently spread through much of the Americas and has been associated mostly with microcephaly and other congenital neurologic complications. Encephalitis occurring in infected adults has also been recently reported. This review will discuss the neuropathogenesis of these viruses, their transmission and geographic distribution, the spectrum of their neurologic manifestations, and the appropriate method of diagnosis.

The National Bio- and Agro-Defense Facility: Issues for Congress

DTIC Science & Technology

2007-09-04

example, research on Nipah virus must be performed in a BSL-4 laboratory. diagnostic capabilities for foreign animal and zoonotic diseases.”4 The...fever, African swine fever, Rift Valley fever, Nipah virus, Hendra virus, contagious bovine pleuropneumonia, and Japanese encephalitis.9 The DHS plans

A Molecularly Cloned, Live-Attenuated Japanese Encephalitis Vaccine SA14-14-2 Virus: A Conserved Single Amino Acid in the ij Hairpin of the Viral E Glycoprotein Determines Neurovirulence in Mice

PubMed Central

Kim, Jin-Kyoung; Yun, Gil-Nam; Lee, Eun-Young; Li, Long; Kuhn, Richard J.; Rossmann, Michael G.; Morrey, John D.; Lee, Young-Min

2014-01-01

Japanese encephalitis virus (JEV), a mosquito-borne flavivirus that causes fatal neurological disease in humans, is one of the most important emerging pathogens of public health significance. JEV represents the JE serogroup, which also includes West Nile, Murray Valley encephalitis, and St. Louis encephalitis viruses. Within this serogroup, JEV is a vaccine-preventable pathogen, but the molecular basis of its neurovirulence remains unknown. Here, we constructed an infectious cDNA of the most widely used live-attenuated JE vaccine, SA14-14-2, and rescued from the cDNA a molecularly cloned virus, SA14-14-2MCV, which displayed in vitro growth properties and in vivo attenuation phenotypes identical to those of its parent, SA14-14-2. To elucidate the molecular mechanism of neurovirulence, we selected three independent, highly neurovirulent variants (LD50, <1.5 PFU) from SA14-14-2MCV (LD50, >1.5×105 PFU) by serial intracerebral passage in mice. Complete genome sequence comparison revealed a total of eight point mutations, with a common single G1708→A substitution replacing a Gly with Glu at position 244 of the viral E glycoprotein. Using our infectious SA14-14-2 cDNA technology, we showed that this single Gly-to-Glu change at E-244 is sufficient to confer lethal neurovirulence in mice, including rapid development of viral spread and tissue inflammation in the central nervous system. Comprehensive site-directed mutagenesis of E-244, coupled with homology-based structure modeling, demonstrated a novel essential regulatory role in JEV neurovirulence for E-244, within the ij hairpin of the E dimerization domain. In both mouse and human neuronal cells, we further showed that the E-244 mutation altered JEV infectivity in vitro, in direct correlation with the level of neurovirulence in vivo, but had no significant impact on viral RNA replication. Our results provide a crucial step toward developing novel therapeutic and preventive strategies against JEV and possibly other encephalitic flaviviruses. PMID:25077483

Japanese encephalitis virus/yellow fever virus chimera is safe and confers full protection against yellow fever virus in intracerebrally challenged mice.

PubMed

Yang, Huiqiang; Yang, Huan; Li, Zhushi; Liu, Lina; Wang, Wei; He, Ting; Fan, Fengming; Sun, Yan; Liu, Jie; Li, Yuhua; Zeng, Xianwu

2018-04-25

Yellow fever (YF) is an acute viral haemorrhagic disease caused by the yellow fever virus (YFV), which remains a potential threat to public health. The live-attenuated YF vaccine (17D strain) is a safe and highly effective measure against YF. However, increasing adverse events have been associated with YF vaccinations in recent years; thus, safer, alternative vaccines are needed. In this study, using the Japanese encephalitis live vaccine strain SA14-14-2 as a backbone, a novel chimeric virus was constructed by replacing the pre-membrane (prM) and envelope (E) genes with their YFV 17D counterparts.The chimeric virus exhibited a reduced growth rate and a much smaller plaque morphology than did either parental virus. Furthermore, the chimera was much less neurovirulent than was YF17D and protected mice that were challenged with a lethal dose of the YF virus. These results suggest that this chimera has potential as a novel attenuated YF vaccine. Copyright © 2018 Elsevier Ltd. All rights reserved.

[Experimental monkey encephalitis caused by Powassan virus].

PubMed

Frolova, M P; Isachkova, L M; Shestopalova, N M; Pogodina, V V

1981-01-01

A comparative study of the experimental infection of monkeys caused by brain P-40 of Powassan virus isolated in the Primorye Territory of the USSR and by the prototype Canadian strain LB was carried out. Powassan virus was found to be pathogenic for Macaca rhesus. Clinical and pathomorphological picture of the experimental encephalitis was studied. Full identity of the infection caused in the monkeys by the strain P-40 and the Canadian strain LB of Powassan virus has been proved. On electronmicroscopic examination of the central nervous system the virus was detected in the neurons, glial cells and intercellular spaces. The virions of the strains studied have identical morphological parameters, being 37 to 45 nm in diameter and having spherical shape. The data obtained point to a marked neurotropism of the virus. They will contribute to elucidation of the virus role in the infectious pathology of man, and namely, in verification of encephalitis cases not associated etiologically with the virus of the spring-summer tick-borne encephalitis.

[The clinico-epidemiological characteristics of Powassan encephalitis in the southern Soviet Far East].

PubMed

Leonova, G N; Sorokina, M N; Krugliak, S P

1991-03-01

The present communication deals with the analysis of 14 cases of Powassan encephalitis. As shown in this study, the course of this infection may be accompanied by symptoms indicating the presence of cerebral and meningeal lesions (in 7 cases meningoencephalitic forms with one fatal outcome and in 2 cases meningeal forms were registered) or take febrile and inapparent forms (5 cases). Powassan encephalitis was found to give characteristic symptoms of cerebellovestibular lesions, differentiating this disease from tick-borne encephalitis (TBE). The cases of mixed infections caused by TBE virus, Powassan encephalitis virus and tick-born Borrelia were found to be possible.

The National Bio- and Agro-Defense Facility: Issues for Congress

DTIC Science & Technology

2007-09-10

bmbl5toc.htm]. 7 For example, research on Nipah virus must be performed in a BSL-4 laboratory. 8 71 Federal Register 3107-3109. agent characterization...African swine fever, Rift Valley fever, Nipah virus, Hendra virus, contagious bovine pleuropneumonia, and Japanese encephalitis.9 The DHS plans to

Unusual presentation of a severely ill patient having severe fever with thrombocytopenia syndrome: a case report.

PubMed

Kaneko, Masahiko; Maruta, Masaki; Shikata, Hisaharu; Asou, Kengo; Shinomiya, Hiroto; Suzuki, Tadaki; Hasegawa, Hideki; Shimojima, Masayuki; Saijo, Masayuki

2017-02-03

Severe fever with thrombocytopenia syndrome is an emerging infectious disease caused by a novel phlebovirus belonging to the family Bunyaviridate. Emergence of encephalitis/encephalopathy during severe fever with thrombocytopenia syndrome progression has been identified as a major risk factor associated with a poor prognosis. Here we report the case of a severely ill patient with severe fever with thrombocytopenia syndrome virus-associated encephalitis/encephalopathy characterized by a lesion of the splenium, which resolved later. A 56-year-old Japanese man presented with fever and diarrhea, followed by dysarthria. Diffusion-weighted magnetic resonance imaging demonstrated high signal intensity in the splenium of the corpus callosum. The severe fever with thrombocytopenia syndrome virus genome was detected in our patient's serum, and the clinical course was characterized by convulsion, stupor, and hemorrhagic manifestations, with disseminated intravascular coagulation and hemophagocytic lymphohistiocytosis. Supportive therapy not including administration of corticosteroids led to gradual improvement of the clinical and laboratory findings, and magnetic resonance imaging demonstrated resolution of the splenial lesion. The serum severe fever with thrombocytopenia syndrome viral copy number, which was determined with the quantitative reverse-transcription polymerase chain reaction, rapidly decreased despite the severe clinical course. Our patient's overall condition improved, allowing him to be eventually discharged. Patients with encephalitis/encephalopathy due to severe fever with thrombocytopenia syndrome virus infection may have a favorable outcome, even if they exhibit splenial lesions and a severe clinical course; monitoring the serum viral load may be of value for prediction of outcome and potentially enables the avoidance of corticosteroids to intentionally cause opportunistic infection.

Viruses in reptiles.

PubMed

Ariel, Ellen

2011-09-21

The etiology of reptilian viral diseases can be attributed to a wide range of viruses occurring across different genera and families. Thirty to forty years ago, studies of viruses in reptiles focused mainly on the zoonotic potential of arboviruses in reptiles and much effort went into surveys and challenge trials of a range of reptiles with eastern and western equine encephalitis as well as Japanese encephalitis viruses. In the past decade, outbreaks of infection with West Nile virus in human populations and in farmed alligators in the USA has seen the research emphasis placed on the issue of reptiles, particularly crocodiles and alligators, being susceptible to, and reservoirs for, this serious zoonotic disease. Although there are many recognised reptilian viruses, the evidence for those being primary pathogens is relatively limited. Transmission studies establishing pathogenicity and cofactors are likewise scarce, possibly due to the relatively low commercial importance of reptiles, difficulties with the availability of animals and permits for statistically sound experiments, difficulties with housing of reptiles in an experimental setting or the inability to propagate some viruses in cell culture to sufficient titres for transmission studies. Viruses as causes of direct loss of threatened species, such as the chelonid fibropapilloma associated herpesvirus and ranaviruses in farmed and wild tortoises and turtles, have re-focused attention back to the characterisation of the viruses as well as diagnosis and pathogenesis in the host itself.

The olfactory nerve: a shortcut for influenza and other viral diseases into the central nervous system.

PubMed

van Riel, Debby; Verdijk, Rob; Kuiken, Thijs

2015-01-01

The olfactory nerve consists mainly of olfactory receptor neurons and directly connects the nasal cavity with the central nervous system (CNS). Each olfactory receptor neuron projects a dendrite into the nasal cavity on the apical side, and on the basal side extends its axon through the cribriform plate into the olfactory bulb of the brain. Viruses that can use the olfactory nerve as a shortcut into the CNS include influenza A virus, herpesviruses, poliovirus, paramyxoviruses, vesicular stomatitis virus, rabies virus, parainfluenza virus, adenoviruses, Japanese encephalitis virus, West Nile virus, chikungunya virus, La Crosse virus, mouse hepatitis virus, and bunyaviruses. However, mechanisms of transport via the olfactory nerve and subsequent spread through the CNS are poorly understood. Proposed mechanisms are either infection of olfactory receptor neurons themselves or diffusion through channels formed by olfactory ensheathing cells. Subsequent virus spread through the CNS could occur by multiple mechanisms, including trans-synaptic transport and microfusion. Viral infection of the CNS can lead to damage from infection of nerve cells per se, from the immune response, or from a combination of both. Clinical consequences range from nervous dysfunction in the absence of histopathological changes to severe meningoencephalitis and neurodegenerative disease. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Analysis of ChimeriVax Japanese Encephalitis Virus envelope for T-cell epitopes and comparison to circulating strain sequences.

PubMed

De Groot, Anne S; Martin, William; Moise, Leonard; Guirakhoo, Farshad; Monath, Thomas

2007-11-19

T-cell epitope variability is associated with viral immune escape and may influence the outcome of vaccination against the highly variable Japanese Encephalitis Virus (JEV). We computationally analyzed the ChimeriVax-JEV vaccine envelope sequence for T helper epitopes that are conserved in 12 circulating JEV strains and discovered 75% conservation among putative epitopes. Among non-identical epitopes, only minor amino acid changes that would not significantly affect HLA-binding were present. Therefore, in most cases, circulating strain epitopes could be restricted by the same HLA and are likely to stimulate a cross-reactive T-cell response. Based on this analysis, we predict no significant abrogation of ChimeriVax-JEV-conferred protection against circulating JEV strains.

[Epidemiology of encephalitis caused by arbovirus in the Brazilian Amazonia].

PubMed

Vasconcelos, P F; Da Rosa, J F; Da Rosa, A P; Dégallier, N; Pinheiro, F de P; Sá Filho, G C

1991-01-01

An overview of ecological, epidemiological and clinical findings of potential arthropod-borne encephalitis viruses circulating in the Amazon Region of Brazil are discussed. These viruses are the Eastern Equine Encephalitis (EEE), Western Equine Encephalitis (WEE), St. Louis Encephalitis (SLE), Mucambo (MUC) and Pixuna (PIX). These last two are subtypes (III and IV) of Venezuelan Equine Encephalitis virus. The areas of study were the highways and projects of development, as well as places where outbreaks of human diseases caused by arboviruses had been detected. These viruses are widespread in all Amazonia, and at least four of them, EEE, WEE, SLE and MUC are pathogenic to man. EEE and WEE infections were detected by serology, while SLE and MUC by either serology and virus isolation. The PIX virus has the lowest prevalence and, it was isolated in only a few cases, one being from a laboratory infection. Wild birds are the main hosts for all these viruses, except MUC, whose major hosts are rodents. The symptoms presented by infected people were generally a mild febrile illness. Although, jaundice was observed in two individuals from whom SLE was isolated. A comparison of the clinical symptoms presented by the patients in the Amazon Region and other areas of America, especially in the USA is made. In Brazilian Amazon region epidemics have not been detected although, at least, one EEE epizootic was recorded in Bragança, Para State, in 1960. At that time, of 500 horses that were examined 61% were positive to EEE by HI and of them 8.2% died. On the other hand, SLE has caused four epizootics in a forest near Belem. Wild birds and sentinel monkeys were infected, but no human cases were reported.

Structure and function of the Zika virus full-length NS5 protein

DOE PAGES

Zhao, Baoyu; Yi, Guanghui; Du, Fenglei; ...

2017-03-27

The recent outbreak of Zika virus (ZIKV) has infected over 1 million people in over 30 countries. ZIKV replicates its RNA genome using virally encoded replication proteins. Nonstructural protein 5 (NS5) contains a methyltransferase for RNA capping and a polymerase for viral RNA synthesis. Here we report the crystal structures of full-length NS5 and its polymerase domain at 3.0 Å resolution. The NS5 structure has striking similarities to the NS5 protein of the related Japanese encephalitis virus. The methyltransferase contains in-line pockets for substrate binding and the active site. Key residues in the polymerase are located in similar positions tomore » those of the initiation complex for the hepatitis C virus polymerase. The polymerase conformation is affected by the methyltransferase, which enables a more efficiently elongation of RNA synthesis in vitro. Altogether, our results will contribute to future studies on ZIKV infection and the development of inhibitors of ZIKV replication.« less

Characterization of Rabensburg Virus, a Flavivirus Closely Related to West Nile Virus of the Japanese Encephalitis Antigenic Group

PubMed Central

Aliota, Matthew T.; Jones, Susan A.; Dupuis, Alan P.; Ciota, Alexander T.; Hubalek, Zdenek; Kramer, Laura D.

2012-01-01

Rabensburg virus (RABV), a Flavivirus with ∼76% nucleotide and 90% amino acid identity with representative members of lineage one and two West Nile virus (WNV), previously was isolated from Culex pipiens and Aedes rossicus mosquitoes in the Czech Republic, and phylogenetic and serologic analyses demonstrated that it was likely a new lineage of WNV. However, no direct link between RABV and human disease has been definitively established and the extent to which RABV utilizes the typical WNV transmission cycle is unknown. Herein, we evaluated vector competence and capacity for vertical transmission (VT) in Cx. pipiens; in vitro growth on avian, mammalian, and mosquito cells; and infectivity and viremia production in birds. RABV infection and replication only were detected on mosquito cells. Experimentally inoculated birds did not become infected. Cx. pipiens had poor peroral vector competence and a higher VT rate as compared to US-WNV in Cx. pipiens. As a result, we postulate that RABV is an intermediate between the mosquito-specific and horizontally transmitted flaviviruses. PMID:22724010

Infection of Macaca Radiata with Viruses of the Tick-Borne Encephalitis Group

DTIC Science & Technology

1992-01-01

3411 IC Microbial Patho genesis 1 992, 13: 399 409 ET AD-A265 505 N9 3U 9312898 I Infection of Macaca radiata with viruses of the tick - borne...Diseases, Frederick, MD 21702-5011, U.SA.), M. K. Rippy, K. T. McKee Jr., P. M. Zack and C. J. Peters. Infection of Macaca radiata with viruses of the tick ...for human disease caused by other, related strains of this group of viruses. Key words: Macaca radiata; tick -borne encephalitis; pathogenesis; Kyasanur

A highly pathogenic porcine reproductive and respiratory syndrome virus candidate vaccine based on Japanese encephalitis virus replicon system

PubMed Central

Huang, Lihong; Liu, Shukai; Zang, Fuyu; Xing, Jinchao; Zhang, Youyue; Liang, Jiaqi; Zhang, Guihong

2017-01-01

In the swine industry, porcine reproductive and respiratory syndrome (PRRS) is a highly contagious disease which causes heavy economic losses worldwide. Effective prevention and disease control is an important issue. In this study, we described the construction of a Japanese encephalitis virus (JEV) DNA-based replicon with a cytomegalovirus (CMV) promoter based on the genome of Japanese encephalitis live vaccine virus SA14-14-2, which is capable of offering a potentially novel way to develop and produce vaccines against a major pathogen of global health. This JEV DNA-based replicon contains a large deletion in the structural genes (C-prM-E). A PRRSV GP5/M was inserted into the deletion position of JEV DNA-based replicons to develop a chimeric replicon vaccine candidate for PRRSV. The results showed that BALB/c mice models with the replicon vaccines pJEV-REP-G-2A-M-IRES and pJEV-REP-G-2A-M stimulated antibody responses and induced a cellular immune response. Analysis of ELSA data showed that vaccination with the replicon vaccine expressing GP5/M induced a better antibodies response than traditional DNA vaccines. Therefore, the results suggested that this ectopic expression system based on JEV DNA-based replicons may represent a useful molecular platform for various biological applications, and the JEV DNA-based replicons expressing GP5/M can be further developed into a novel, safe vaccine candidate for PRRS. PMID:28740748

Pathology of whooper swans (Cygnus cygnus) infected with H5N1 avian influenza virus in Akita, Japan, in 2008.

PubMed

Ogawa, Shuji; Yamamoto, Yu; Yamada, Manabu; Mase, Masaji; Nakamura, Kikuyasu

2009-10-01

Two (1 adult and 1 young bird) of 4 H5N1-highly-pathogenic-avian-influenza (HPAI)-virus-infected whooper swans in Akita, Japan, in 2008 were investigated pathologically. Macroscopically, white spots with hemorrhages were scattered in the pancreas in the adult bird. Histologically, the adult bird had severe necrotizing pancreatitis and mild nonpurulent encephalitis. The young bird had severe nonpurulent encephalitis and nonpurulent enteric ganglionitis, and intestinal venous wall thickening. Virus antigens were detected in the lesions of pancreatitis in the adult bird and of encephalitis in adult and young birds. These findings suggest that the swans died or became moribund due to neurological disorders and necrotizing pancreatitis caused by H5N1 HPAI virus infection.

Distinction between serological responses following tick-borne encephalitis virus (TBEV) infection vs vaccination, Sweden 2017.

PubMed

Albinsson, Bo; Vene, Sirkka; Rombo, Lars; Blomberg, Jonas; Lundkvist, Åke; Rönnberg, Bengt

2018-01-01

Tick-borne encephalitis virus (TBEV) is an important European vaccine-preventable pathogen. Discrimination of vaccine-induced antibodies from those elicited by infection is important. We studied anti-TBEV IgM/IgG responses, including avidity and neutralisation, by multiplex serology in 50 TBEV patients and 50 TBEV vaccinees. Infection induced antibodies reactive to both whole virus (WV) and non-structural protein 1 (NS1) in 48 clinical cases, whereas 47 TBEV vaccinees had WV, but not NS1 antibodies, enabling efficient discrimination of infection/vaccination.

IMOJEV(®): a Yellow fever virus-based novel Japanese encephalitis vaccine.

PubMed

Appaiahgari, Mohan Babu; Vrati, Sudhanshu

2010-12-01

Japanese encephalitis (JE) is a disease of the CNS caused by Japanese encephalitis virus (JEV). The disease appears in the form of frequent outbreaks in most south- and southeast Asian countries and the virus has become endemic in several areas. There is no licensed therapy available and disease control by vaccination is considered to be most effective. Mouse brain-derived inactivated JE vaccines, although immunogenic, have several limitations in terms of safety, availability and requirement for multiple doses. Owing to these drawbacks, the WHO called for the development of novel, safe and more efficacious JE vaccines. Several candidate vaccines have been developed and at least three of them that demonstrated strong immunogenicity after one or two doses of the vaccine in animal models were subsequently tested in various clinical trials. One of these vaccines, IMOJEV(®) (JE-CV and previously known as ChimeriVax™-JE), is a novel recombinant chimeric virus vaccine, developed using the Yellow fever virus (YFV) vaccine vector YFV17D, by replacing the cDNA encoding the envelope proteins of YFV with that of an attenuated JEV strain SA14-14-2. IMOJEV was found to be safe, highly immunogenic and capable of inducing long-lasting immunity in both preclinical and clinical trials. Moreover, a single dose of IMOJEV was sufficient to induce protective immunity, which was similar to that induced in adults by three doses of JE-VAX(®), a mouse brain-derived inactivated JE vaccine. Recently, Phase III trials evaluating the immunogenicity and safety of the chimeric virus vaccine have been successfully completed in some JE-endemic countries and the vaccine manufacturers have filed an application for vaccine registration. IMOJEV may thus be licensed for use in humans as an improved alternative to the currently licensed JE vaccines.

Serologic Evidence of Tick-Borne Encephalitis Virus Infection in a Patient with Suspected Lyme Disease in Japan.

PubMed

Yoshii, Kentaro; Sato, Kozue; Ishizuka, Mariko; Kobayashi, Shintaro; Kariwa, Hiroaki; Kawabata, Hiroki

2018-05-29

Tick-borne encephalitis (TBE) is widely prevalent on the Eurasian continent, including Japan, but four cases of TBE have been reported in Japan. To inspect unconfirmed TBE cases in Japan, we conducted a retrospective seroepidemiological study of a total of 158 samples from 81 meningoencephalitis patients suspected as Lyme disease. Two serum samples from one patient showed neutralizing antibodies against TBE virus. The patient with severe and progressive encephalitis had a history of tick bite in Hokkaido in 2012. These results demonstrated that tick-borne encephalitis virus (TBEV) case was actually unconfirmed in Japan. Further seroepidemiological surveys are required to identify unconfirmed TBEV infections to consider the pros and cons of introducing specific countermeasures including vaccination in Japan.

Comparing the immunogenicity and safety of 3 Japanese encephalitis vaccines in Asia-Pacific area: A systematic review and meta-analysis.

PubMed

Wang, Shi-Yuan; Cheng, Xiao-Hua; Li, Jing-Xin; Li, Xi-Yan; Zhu, Feng-Cai; Liu, Pei

2015-01-01

Japanese encephalitis virus (JEV), a leading cause of Japanese encephalitis (JE) in children and adults, is a major public health problem in Asian countries. This study reports a meta-analysis of the immunogenicity and safety of vaccines used to protect infants or children from JE. Three types of JE vaccine were examined, namely, Japanese encephalitis live-attenuated vaccine (JEV-L), Japanese encephalitis inactivated vaccine (Vero cell) (JEV-I(Vero)), and Japanese encephalitis inactivated vaccine (primary hamster kidney cell) (JEV-I(PHK)). These vaccines are used to induce fundamental immunity against JE; however, few studies have compared their immunogenicity and safety in infants and young children less than 2 years of age. Data were obtained by searching 5 databases: Web of Science, PubMed, China National Knowledge Infrastructure, the China Wanfang database, and the Cochrane database. Fifteen articles were identified and scored using the Jadad score for inclusion in the meta-analysis. Random effect models were used to calculate the pooled seroconversion rate and adverse reaction rate when tests for heterogeneity were significant. The results showed that the pooled seroconversion rate for JEV-I(PHK) (62.23%) was lower than that for JEV-I(Vero) (86.49%) and JEV-L (83.52%), and that the pooled adverse reaction rate for JEV-L (18.09%) was higher than that for JEV-I(PHK) (10.08%) and JEV-I(Vero) (12.49%). The pooled relative risk was then calculated to compare the seroconversion and adverse reaction rates. The results showed that JEV-I(Vero) and JEV-L were more suitable than JEV-I(PHK) for inducing fundamental immunity to JE in infants and children less than 2 years of age.

West Nile Virus Encephalitis: The First Human Case Recorded in Brazil

PubMed Central

Vieira, Marcelo A. C. S.; Romano, Alessandro P. M.; Borba, Amaríles S.; Silva, Eliana V. P.; Chiang, Jannifer O.; Eulálio, Kelsen D.; Azevedo, Raimunda S. S.; Rodrigues, Sueli G.; Almeida-Neto, Walfrido S.; Vasconcelos, Pedro F. C.

2015-01-01

A Brazilian ranch worker with encephalitis and flaccid paralysis was evaluated in the regional Acute Encephalitis Syndromic Surveillance Program. This was the first Brazilian patient who met the Centers for Disease Control and Prevention (CDC) confirmation criteria for West Nile virus disease. Owing to the overlapping of neurological manifestations attributable to several viral infections of the central nervous system, this report exemplifies the importance of human acute encephalitis surveillance. The syndromic approach to human encephalitis cases may enable early detection of the introduction of unusual virus or endemic occurrence of potentially alarming diseases within a region. PMID:26055749

Variation of the Specificity of the Human Antibody Responses after Tick-Borne Encephalitis Virus Infection and Vaccination

PubMed Central

Jarmer, Johanna; Zlatkovic, Jürgen; Tsouchnikas, Georgios; Vratskikh, Oksana; Strauß, Judith; Aberle, Judith H.; Chmelik, Vaclav; Kundi, Michael; Stiasny, Karin

2014-01-01

ABSTRACT Tick-borne encephalitis (TBE) virus is an important human-pathogenic flavivirus endemic in large parts of Europe and Central and Eastern Asia. Neutralizing antibodies specific for the viral envelope protein E are believed to mediate long-lasting protection after natural infection and vaccination. To study the specificity and individual variation of human antibody responses, we developed immunoassays with recombinant antigens representing viral surface protein domains and domain combinations. These allowed us to dissect and quantify antibody populations of different fine specificities in sera of TBE patients and vaccinees. Postinfection and postvaccination sera both displayed strong individual variation of antibody titers as well as the relative proportions of antibodies to different domains of E, indicating that the immunodominance patterns observed were strongly influenced by individual-specific factors. The contributions of these antibody populations to virus neutralization were quantified by serum depletion analyses and revealed a significantly biased pattern. Antibodies to domain III, in contrast to what was found in mouse immunization studies with TBE and other flaviviruses, did not play any role in the human neutralizing antibody response, which was dominated by antibodies to domains I and II. Importantly, most of the neutralizing activity could be depleted from sera by a dimeric soluble form of the E protein, which is the building block of the icosahedral herringbone-like shell of flaviviruses, suggesting that antibodies to more complex quaternary epitopes involving residues from adjacent dimers play only a minor role in the total response to natural infection and vaccination in humans. IMPORTANCE Tick-borne encephalitis (TBE) virus is a close relative of yellow fever, dengue, Japanese encephalitis, and West Nile viruses and distributed in large parts of Europe and Central and Eastern Asia. Antibodies to the viral envelope protein E prevent viral attachment and entry into cells and thus mediate virus neutralization and protection from disease. However, the fine specificity and individual variation of neutralizing antibody responses are currently not known. We have therefore developed new in vitro assays for dissecting the antibody populations present in blood serum and determining their contribution to virus neutralization. In our analysis of human postinfection and postvaccination sera, we found an extensive variation of the antibody populations present in sera, indicating substantial influences of individual-specific factors that control the specificity of the antibody response. Our study provides new insights into the immune response to an important human pathogen that is of relevance for the design of novel vaccines. PMID:25253341

Variation of the specificity of the human antibody responses after tick-borne encephalitis virus infection and vaccination.

PubMed

Jarmer, Johanna; Zlatkovic, Jürgen; Tsouchnikas, Georgios; Vratskikh, Oksana; Strauß, Judith; Aberle, Judith H; Chmelik, Vaclav; Kundi, Michael; Stiasny, Karin; Heinz, Franz X

2014-12-01

Tick-borne encephalitis (TBE) virus is an important human-pathogenic flavivirus endemic in large parts of Europe and Central and Eastern Asia. Neutralizing antibodies specific for the viral envelope protein E are believed to mediate long-lasting protection after natural infection and vaccination. To study the specificity and individual variation of human antibody responses, we developed immunoassays with recombinant antigens representing viral surface protein domains and domain combinations. These allowed us to dissect and quantify antibody populations of different fine specificities in sera of TBE patients and vaccinees. Postinfection and postvaccination sera both displayed strong individual variation of antibody titers as well as the relative proportions of antibodies to different domains of E, indicating that the immunodominance patterns observed were strongly influenced by individual-specific factors. The contributions of these antibody populations to virus neutralization were quantified by serum depletion analyses and revealed a significantly biased pattern. Antibodies to domain III, in contrast to what was found in mouse immunization studies with TBE and other flaviviruses, did not play any role in the human neutralizing antibody response, which was dominated by antibodies to domains I and II. Importantly, most of the neutralizing activity could be depleted from sera by a dimeric soluble form of the E protein, which is the building block of the icosahedral herringbone-like shell of flaviviruses, suggesting that antibodies to more complex quaternary epitopes involving residues from adjacent dimers play only a minor role in the total response to natural infection and vaccination in humans. Tick-borne encephalitis (TBE) virus is a close relative of yellow fever, dengue, Japanese encephalitis, and West Nile viruses and distributed in large parts of Europe and Central and Eastern Asia. Antibodies to the viral envelope protein E prevent viral attachment and entry into cells and thus mediate virus neutralization and protection from disease. However, the fine specificity and individual variation of neutralizing antibody responses are currently not known. We have therefore developed new in vitro assays for dissecting the antibody populations present in blood serum and determining their contribution to virus neutralization. In our analysis of human postinfection and postvaccination sera, we found an extensive variation of the antibody populations present in sera, indicating substantial influences of individual-specific factors that control the specificity of the antibody response. Our study provides new insights into the immune response to an important human pathogen that is of relevance for the design of novel vaccines. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Neurologic Complications of Influenza B Virus Infection in Adults, Romania.

PubMed

Popescu, Corneliu P; Florescu, Simin A; Lupulescu, Emilia; Zaharia, Mihaela; Tardei, Gratiela; Lazar, Mihaela; Ceausu, Emanoil; Ruta, Simona M

2017-04-01

We characterized influenza B virus-related neurologic manifestations in an unusually high number of hospitalized adults at a tertiary care facility in Romania during the 2014-15 influenza epidemic season. Of 32 patients with a confirmed laboratory diagnosis of influenza B virus infection, neurologic complications developed in 7 adults (median age 31 years). These complications were clinically diagnosed as confirmed encephalitis (4 patients), possible encephalitis (2 patients), and cerebellar ataxia (1 patient). Two of the patients died. Virus sequencing identified influenza virus B (Yam)-lineage clade 3, which is representative of the B/Phuket/3073/2013 strain, in 4 patients. None of the patients had been vaccinated against influenza. These results suggest that influenza B virus can cause a severe clinical course and should be considered as an etiologic factor for encephalitis.

Purification and crystallization of Kokobera virus helicase

DOE Office of Scientific and Technical Information (OSTI.GOV)

De Colibus, Luigi; Speroni, Silvia; Coutard, Bruno

2007-03-01

Kokobera virus is a mosquito-borne flavivirus belonging, like West Nile virus, to the Japanese encephalitis virus serocomplex. Crystals of the Kokobera virus helicase domain were obtained by the hanging-drop vapour-diffusion method and exhibit a diffraction limit of 2.3 Å. Kokobera virus is a mosquito-borne flavivirus belonging, like West Nile virus, to the Japanese encephalitis virus serocomplex. The flavivirus genus is characterized by a positive-sense single-stranded RNA genome. The unique open reading frame of the viral RNA is transcribed and translated as a single polyprotein which is post-translationally cleaved to yield three structural and seven nonstructural proteins, one of which ismore » the NS3 gene that encodes a C-terminal helicase domain consisting of 431 amino acids. Helicase inhibitors are potential antiviral drugs as the helicase is essential to viral replication. Crystals of the Kokobera virus helicase domain were obtained by the hanging-drop vapour-diffusion method. The crystals belong to space group P3{sub 1}21 (or P3{sub 2}21), with unit-cell parameters a = 88.6, c = 138.6 Å, and exhibit a diffraction limit of 2.3 Å.« less

A Japanese Encephalitis Virus Peptide Present on Johnson Grass Mosaic Virus-Like Particles Induces Virus-Neutralizing Antibodies and Protects Mice against Lethal Challenge

PubMed Central

Saini, Manisha; Vrati, Sudhanshu

2003-01-01

Protection against Japanese encephalitis virus (JEV) is antibody dependent, and neutralizing antibodies alone are sufficient to impart protection. Thus, we are aiming to develop a peptide-based vaccine against JEV by identifying JEV peptide sequences that could induce virus-neutralizing antibodies. Previously, we have synthesized large amounts of Johnson grass mosaic virus (JGMV) coat protein (CP) in Escherichia coli and have shown that it autoassembled to form virus-like particles (VLPs). The envelope (E) protein of JEV contains the virus-neutralization epitopes. Four peptides from different locations within JEV E protein were chosen, and these were fused to JGMV CP by recombinant DNA methods. The fusion protein autoassembled to form VLPs that could be purified by sucrose gradient centrifugation. Immunization of mice with the recombinant VLPs containing JEV peptide sequences induced anti-peptide and anti-JEV antibodies. A 27-amino-acid peptide containing amino acids 373 to 399 from JEV E protein, present on JGMV VLPs, induced virus-neutralizing antibodies. Importantly, these antibodies were obtained without the use of an adjuvant. The immunized mice showed significant protection against a lethal JEV challenge. PMID:12610124

Crystal structure of full-length Zika virus NS5 protein reveals a conformation similar to Japanese encephalitis virus NS5

DOE Office of Scientific and Technical Information (OSTI.GOV)

Upadhyay, Anup K.; Cyr, Matthew; Longenecker, Kenton

The rapid spread of the recentZika virus(ZIKV) epidemic across various countries in the American continent poses a major health hazard for the unborn fetuses of pregnant women. To date, there is no effective medical intervention. The nonstructural protein 5 ofZika virus(ZIKV-NS5) is critical for ZIKV replication through the 5'-RNA capping and RNA polymerase activities present in its N-terminal methyltransferase (MTase) and C-terminal RNA-dependent RNA polymerase (RdRp) domains, respectively. The crystal structure of the full-length ZIKV-NS5 protein has been determined at 3.05 Å resolution from a crystal belonging to space groupP2 12 12 and containing two protein molecules in the asymmetricmore » unit. The structure is similar to that reported for the NS5 protein fromJapanese encephalitis virusand suggests opportunities for structure-based drug design targeting either its MTase or RdRp domain.« less

Diagnosis of Zika Virus Infection by Peptide Array and Enzyme-Linked Immunosorbent Assay.

PubMed

Mishra, Nischay; Caciula, Adrian; Price, Adam; Thakkar, Riddhi; Ng, James; Chauhan, Lokendra V; Jain, Komal; Che, Xiaoyu; Espinosa, Diego A; Montoya Cruz, Magelda; Balmaseda, Angel; Sullivan, Eric H; Patel, Jigar J; Jarman, Richard G; Rakeman, Jennifer L; Egan, Christina T; Reusken, Chantal B E M; Koopmans, Marion P G; Harris, Eva; Tokarz, Rafal; Briese, Thomas; Lipkin, W Ian

2018-03-06

Zika virus (ZIKV) is implicated in fetal stillbirth, microcephaly, intracranial calcifications, and ocular anomalies following vertical transmission from infected mothers. In adults, infection may trigger autoimmune inflammatory polyneuropathy. Transmission most commonly follows the bite of infected Aedes mosquitoes but may also occur through sexual intercourse or receipt of blood products. Definitive diagnosis through detection of viral RNA is possible in serum or plasma within 10 days of disease onset, in whole blood within 3 weeks of onset, and in semen for up to 3 months. Serological diagnosis is nonetheless critical because few patients have access to molecular diagnostics during the acute phase of infection and infection may be associated with only mild or inapparent disease that does not prompt molecular testing. Serological diagnosis is confounded by cross-reactivity of immune sera with other flaviviruses endemic in the areas where ZIKV has recently emerged. Accordingly, we built a high-density microarray comprising nonredundant 12-mer peptides that tile, with one-residue overlap, the proteomes of Zika, dengue, yellow fever, West Nile, Ilheus, Oropouche, and chikungunya viruses. Serological analysis enabled discovery of a ZIKV NS2B 20-residue peptide that had high sensitivity (96.0%) and specificity (95.9%) versus natural infection with or vaccination against dengue, chikungunya, yellow fever, West Nile, tick-borne encephalitis, or Japanese encephalitis virus in a microarray assay and an enzyme-linked immunosorbent assay (ELISA) of early-convalescent-phase sera (2 to 3 weeks after onset of symptomatic infection). IMPORTANCE The emergence of Zika virus (ZIKV) as a teratogen is a profound challenge to global public health. Molecular diagnosis of infection is straightforward during the 3-week period when patients are viremic. However, serological diagnosis thereafter of historical exposure has been confounded by cross-reactivity. Using high-density peptide arrays that tile the proteomes of a selection of flaviviruses to identify a ZIKV-specific peptide, we established two assays that enable sensitive and specific diagnosis of exposure to ZIKV. These assays may be useful in guiding clinical management of mothers at risk for potential exposure to ZIKV and enable insights into the epidemiology of ZIKV infections.

Measles-induced encephalitis.

PubMed

Fisher, D L; Defres, S; Solomon, T

2015-03-01

Encephalitis is the most frequent neurological complication of measles virus infection. This review examines the pathophysiology of measles infection and the presentations, diagnosis and treatment of the four types of measles-induced encephalitis including primary measles encephalitis, acute post-measles encephalitis, measles inclusion body encephalitis and subacute sclerosing panencephalitis. The early symptoms of encephalitis may be non-specific and can be mistakenly attributed to a systemic infection leading to a delay in diagnosis. This review provides a summary of the symptoms that should cause health care workers to suspect measles-induced encephalitis. © The Author 2014. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Effect of cytokine-encoding plasmid delivery on immune response to Japanese encephalitis virus DNA vaccine in mice.

PubMed

Bharati, Kaushik; Appaiahgari, Mohan Babu; Vrati, Sudhanshu

2005-01-01

We have previously shown that immunization of mice with plasmid pMEa synthesizing Japanese encephalitis virus (JEV) envelope protein induced anti-JEV humoral and cellular immune responses. We now show that intra-muscular co-administration of mice with pMEa and pGM-CSF, encoding murine granulocyte-macrophage colony-stimulating factor or pIL-2, encoding murine interleukin-2 given 4 days after pMEa, augmented anti-JEV antibody titers. This did not enhance the level of protection in immunized mice against JEV. However, intra-dermal co-administration of pMEa and pGM-CSF in mice using the gene gun, enhanced anti-JEV antibody titers resulting in an increased level of protection in mice against lethal JEV challenge.

An in vitro recombination-based reverse genetic system for rapid mutagenesis of structural genes of the Japanese encephalitis virus.

PubMed

Du, Ruikun; Wang, Manli; Hu, Zhihong; Wang, Hualin; Deng, Fei

2015-10-01

Japanese encephalitis virus (JEV) is one of the most common pathogens of severe viral encephalitis, which is a severe threat to human health. Despite instability of the JEV genome in bacteria, many strategies have been developed to establish molecular clone systems of JEV, providing convenient tools for studying the virus life cycle and virus-host interactions. In this study, we adapted an In-Fusion enzyme-based in vitro recombination method to construct a reverse genetic system of JEV, thereby providing a rapid approach to introduce mutations into the structural genes. A truncated genome without the structural genes was constructed as the backbone, and the complementary segment containing the structural genes was recombined in vitro, which was then transfected directly into virus-permissive cells. The progeny of the infectious virus was successfully detected in the supernatant of the transfected cells, and showed an identical phenotype to its parental virus. To provide a proof-of-principle, the 12 conserved cysteine residues in the envelope (E) protein of JEV were respectively mutated using this approach, and all mutations resulted in a complete failure to generate infectious virus. However, a leucine-tophenylanine mutation at amino acid 107 of the E protein did not interfere with the production of the infectious virus. These results suggested that all 12 cysteines in the E protein are essential for the JEV life cycle. In summary, a novel reverse genetic system of JEV was established for rapidly introducing mutations into structural genes, which will serve as a useful tool for functional studies.

Unusual Necrotizing Encephalitis in Raccoons and Skunks Concurrently Infected With Canine Distemper Virus and Sarcocystis sp.

PubMed

Kubiski, S V; Sisó, S; Church, M E; Cartoceti, A N; Barr, B; Pesavento, P A

2016-05-01

Canine distemper virus commonly infects free-ranging, terrestrial mesopredators throughout the United States. Due to the immunosuppressive effects of the virus, concurrent opportunistic infections are also common. Among these, secondary systemic protozoal infections have been described in a number of species. We report an unusual presentation of necrotizing encephalitis associated withSarcocystissp in four raccoons and one skunk concurrently infected with canine distemper virus. Lesions were characterized by variably sized necrotizing cavitations composed of abundant mineral admixed with inflammatory cells and protozoa.Sarcocystissp was confirmed via immunohistochemistry using a monoclonal antibody toSarcocystis neurona The pathologic changes are similar to lesions in human AIDS patients infected withToxoplasma gondii. © The Author(s) 2015.

Unrecognized Subclinical Infection with Tickborne Encephalitis Virus, Japan

PubMed Central

Yoshii, Kentaro; Kojima, Reiji

2017-01-01

During early 2017, we conducted a seroepidemiologic investigation for tickborne encephalitis virus among 291 Japan Self-Defense Forces members in Hokkaido. Two (0.7%) tested positive. Neither had clinically apparent symptoms after removing ticks. PMID:28930025

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gardner, S; Jaing, C

The goal of this project is to develop forensic genotyping assays for select agent viruses, addressing a significant capability gap for the viral bioforensics and law enforcement community. We used a multipronged approach combining bioinformatics analysis, PCR-enriched samples, microarrays and TaqMan assays to develop high resolution and cost effective genotyping methods for strain level forensic discrimination of viruses. We have leveraged substantial experience and efficiency gained through year 1 on software development, SNP discovery, TaqMan signature design and phylogenetic signature mapping to scale up the development of forensics signatures in year 2. In this report, we have summarized the Taqmanmore » signature development for South American hemorrhagic fever viruses, tick-borne encephalitis viruses and henipaviruses, Old World Arenaviruses, filoviruses, Crimean-Congo hemorrhagic fever virus, Rift Valley fever virus and Japanese encephalitis virus.« less

Following Acute Encephalitis, Semliki Forest Virus is Undetectable in the Brain by Infectivity Assays but Functional Virus RNA Capable of Generating Infectious Virus Persists for Life.

PubMed

Fragkoudis, Rennos; Dixon-Ballany, Catherine M; Zagrajek, Adrian K; Kedzierski, Lukasz; Fazakerley, John K

2018-05-18

Alphaviruses are mosquito-transmitted RNA viruses which generally cause acute disease including mild febrile illness, rash, arthralgia, myalgia and more severely, encephalitis. In the mouse, peripheral infection with Semliki Forest virus (SFV) results in encephalitis. With non-virulent strains, infectious virus is detectable in the brain, by standard infectivity assays, for around ten days. As we have shown previously, in severe combined immunodeficient (SCID) mice, infectious virus is detectable for months in the brain. Here we show that in MHC-II -/- mice, with no functional CD4 T-cells, infectious virus is also detectable in the brain for long periods. In contrast, in the brains of CD8 -/- mice, virus RNA persists but infectious virus is not detectable. In SCID mice infected with SFV, repeated intraperitoneal administration of anti-SFV immune serum rapidly reduced the titer of infectious virus in the brain to undetectable, however virus RNA persisted. Repeated intraperitoneal passive transfer of immune serum resulted in maintenance of brain virus RNA, with no detectable infectious virus, for several weeks. When passive antibody transfer was stopped, antibody levels declined and infectious virus was again detectable in the brain. In aged immunocompetent mice, previously infected with SFV, immunosuppression of antibody responses many months after initial infection also resulted in renewed ability to detect infectious virus in the brain. In summary, antiviral antibodies control and determine whether infectious virus is detectable in the brain but immune responses cannot clear this infection from the brain. Functional virus RNA capable of generating infectious virus persists and if antibody levels decline, infectious virus is again detectable.

Flavivirus NS3 and NS5 proteins interaction network: a high-throughput yeast two-hybrid screen

PubMed Central

2011-01-01

Background The genus Flavivirus encompasses more than 50 distinct species of arthropod-borne viruses, including several major human pathogens, such as West Nile virus, yellow fever virus, Japanese encephalitis virus and the four serotypes of dengue viruses (DENV type 1-4). Each year, flaviviruses cause more than 100 million infections worldwide, some of which lead to life-threatening conditions such as encephalitis or haemorrhagic fever. Among the viral proteins, NS3 and NS5 proteins constitute the major enzymatic components of the viral replication complex and are essential to the flavivirus life cycle. Results We report here the results of a high-throughput yeast two-hybrid screen to identify the interactions between human host proteins and the flavivirus NS3 and NS5 proteins. Using our screen results and literature curation, we performed a global analysis of the NS3 and NS5 cellular targets based on functional annotation with the Gene Ontology features. We finally created the first flavivirus NS3 and NS5 proteins interaction network and analysed the topological features of this network. Our proteome mapping screen identified 108 human proteins interacting with NS3 or NS5 proteins or both. The global analysis of the cellular targets revealed the enrichment of host proteins involved in RNA binding, transcription regulation, vesicular transport or innate immune response regulation. Conclusions We proposed that the selective disruption of these newly identified host/virus interactions could represent a novel and attractive therapeutic strategy in treating flavivirus infections. Our virus-host interaction map provides a basis to unravel fundamental processes about flavivirus subversion of the host replication machinery and/or immune defence strategy. PMID:22014111

Flavivirus NS3 and NS5 proteins interaction network: a high-throughput yeast two-hybrid screen.

PubMed

Le Breton, Marc; Meyniel-Schicklin, Laurène; Deloire, Alexandre; Coutard, Bruno; Canard, Bruno; de Lamballerie, Xavier; Andre, Patrice; Rabourdin-Combe, Chantal; Lotteau, Vincent; Davoust, Nathalie

2011-10-20

The genus Flavivirus encompasses more than 50 distinct species of arthropod-borne viruses, including several major human pathogens, such as West Nile virus, yellow fever virus, Japanese encephalitis virus and the four serotypes of dengue viruses (DENV type 1-4). Each year, flaviviruses cause more than 100 million infections worldwide, some of which lead to life-threatening conditions such as encephalitis or haemorrhagic fever. Among the viral proteins, NS3 and NS5 proteins constitute the major enzymatic components of the viral replication complex and are essential to the flavivirus life cycle. We report here the results of a high-throughput yeast two-hybrid screen to identify the interactions between human host proteins and the flavivirus NS3 and NS5 proteins. Using our screen results and literature curation, we performed a global analysis of the NS3 and NS5 cellular targets based on functional annotation with the Gene Ontology features. We finally created the first flavivirus NS3 and NS5 proteins interaction network and analysed the topological features of this network. Our proteome mapping screen identified 108 human proteins interacting with NS3 or NS5 proteins or both. The global analysis of the cellular targets revealed the enrichment of host proteins involved in RNA binding, transcription regulation, vesicular transport or innate immune response regulation. We proposed that the selective disruption of these newly identified host/virus interactions could represent a novel and attractive therapeutic strategy in treating flavivirus infections. Our virus-host interaction map provides a basis to unravel fundamental processes about flavivirus subversion of the host replication machinery and/or immune defence strategy.

Epidemiology of Japanese encephalitis in the Philippines: a systematic review.

PubMed

Lopez, Anna Lena; Aldaba, Josephine G; Roque, Vito G; Tandoc, Amado O; Sy, Ava Kristy; Espino, Fe Esperanza; DeQuiroz-Castro, Maricel; Jee, Youngmee; Ducusin, Maria Joyce; Fox, Kimberley K

2015-03-01

Japanese encephalitis virus (JEV) is an important cause of encephalitis in most of Asia, with high case fatality rates and often significant neurologic sequelae among survivors. The epidemiology of JE in the Philippines is not well defined. To support consideration of JE vaccine for introduction into the national schedule in the Philippines, we conducted a systematic literature review and summarized JE surveillance data from 2011 to 2014. We conducted searches on Japanese encephalitis and the Philippines in four databases and one library. Data from acute encephalitis syndrome (AES) and JE surveillance and from the national reference laboratory from January 2011 to March 2014 were tabulated and mapped. We identified 29 published reports and presentations on JE in the Philippines, including 5 serologic surveys, 18 reports of clinical cases, and 8 animal studies (including two with both clinical cases and animal data). The 18 clinical studies reported 257 cases of laboratory-confirmed JE from 1972 to 2013. JE virus (JEV) was the causative agent in 7% to 18% of cases of clinical meningitis and encephalitis combined, and 16% to 40% of clinical encephalitis cases. JE predominantly affected children under 15 years of age and 6% to 7% of cases resulted in death. Surveillance data from January 2011 to March 2014 identified 73 (15%) laboratory-confirmed JE cases out of 497 cases tested. This comprehensive review demonstrates the endemicity and extensive geographic range of JE in the Philippines, and supports the use of JE vaccine in the country. Continued and improved surveillance with laboratory confirmation is needed to systematically quantify the burden of JE, to provide information that can guide prioritization of high risk areas in the country and determination of appropriate age and schedule of vaccine introduction, and to measure the impact of preventive measures including immunization against this important public health threat.

Epidemiology of Japanese Encephalitis in the Philippines: A Systematic Review

PubMed Central

Lopez, Anna Lena; Aldaba, Josephine G.; Roque, Vito G.; Tandoc, Amado O.; Sy, Ava Kristy; Espino, Fe Esperanza; DeQuiroz-Castro, Maricel; Jee, Youngmee; Ducusin, Maria Joyce; Fox, Kimberley K.

2015-01-01

Background Japanese encephalitis virus (JEV) is an important cause of encephalitis in most of Asia, with high case fatality rates and often significant neurologic sequelae among survivors. The epidemiology of JE in the Philippines is not well defined. To support consideration of JE vaccine for introduction into the national schedule in the Philippines, we conducted a systematic literature review and summarized JE surveillance data from 2011 to 2014. Methods We conducted searches on Japanese encephalitis and the Philippines in four databases and one library. Data from acute encephalitis syndrome (AES) and JE surveillance and from the national reference laboratory from January 2011 to March 2014 were tabulated and mapped. Results We identified 29 published reports and presentations on JE in the Philippines, including 5 serologic surveys, 18 reports of clinical cases, and 8 animal studies (including two with both clinical cases and animal data). The 18 clinical studies reported 257 cases of laboratory-confirmed JE from 1972 to 2013. JE virus (JEV) was the causative agent in 7% to 18% of cases of clinical meningitis and encephalitis combined, and 16% to 40% of clinical encephalitis cases. JE predominantly affected children under 15 years of age and 6% to 7% of cases resulted in death. Surveillance data from January 2011 to March 2014 identified 73 (15%) laboratory-confirmed JE cases out of 497 cases tested. Summary This comprehensive review demonstrates the endemicity and extensive geographic range of JE in the Philippines, and supports the use of JE vaccine in the country. Continued and improved surveillance with laboratory confirmation is needed to systematically quantify the burden of JE, to provide information that can guide prioritization of high risk areas in the country and determination of appropriate age and schedule of vaccine introduction, and to measure the impact of preventive measures including immunization against this important public health threat. PMID:25794009

Powassan virus infection: case series and literature review from a single institution.

PubMed

Raval, Mihir; Singhal, Mayank; Guerrero, Dubert; Alonto, Augusto

2012-10-30

Powassan virus is a flavivirus related to eastern hemisphere's tick-borne encephalitis viruses. It can cause a rare but potentially life-threatening disease including encephalitis. We report four cases of POWV infection in Minnesota and North Dakota with known exposure to tick bites in 2011. Our first case was an 18-year-old male who dramatically presented with seizure and headache with positive serum analysis for Powassan virus immunoglobulin M. The second case was a 60 year old gentleman with intraparenchymal hemorrhage and was diagnosed via cerebrospinal fluid analysis. Thirdly, a 61 year old male developed altered mental status and encephalitis. Our fourth patient was a 69 year old male who had headache and non-focal weakness who was diagnosed with serum analysis. Symptoms of Powassan virus infection ranged from headaches to seizures and severe neurological symptoms. This study serves to highlight the increased detection of Powassan virus infection in the central north United States. This report focuses on the increasing incidence that can lead to increasing efforts for raising awareness regarding this infection. There is a need for clinician vigilance and public attention due to its increasing detection, westward progression and varied clinical presentations.

Structure of the recombinant alphavirus Western equine encephalitis virus revealed by cryoelectron microscopy.

PubMed

Sherman, Michael B; Weaver, Scott C

2010-10-01

Western equine encephalitis virus (WEEV; Togaviridae, Alphavirus) is an enveloped RNA virus that is typically transmitted to vertebrate hosts by infected mosquitoes. WEEV is an important cause of viral encephalitis in humans and horses in the Americas, and infection results in a range of disease, from mild flu-like illnesses to encephalitis, coma, and death. In addition to spreading via mosquito vectors, human WEEV infections can potentially occur directly via aerosol transmission. Due to its aerosol infectivity and virulence, WEEV is thus classified as a biological safety level 3 (BSL-3) agent. Because of its highly infectious nature and containment requirements, it has not been possible to investigate WEEV's structure or assembly mechanism using standard structural biology techniques. Thus, to image WEEV and other BSL-3 agents, we have constructed a first-of-its-kind BSL-3 cryoelectron microscopy (cryoEM) containment facility. cryoEM images of WEEV were used to determine the first three-dimensional structure of this important human pathogen. The overall organization of WEEV is similar to those of other alphaviruses, consistent with the high sequence similarity among alphavirus structural proteins. Surprisingly, the nucleocapsid of WEEV, a New World virus, is more similar to the Old World alphavirus Sindbis virus than to other New World alphaviruses.

Venezuelan encephalitis virus infection in neotropical bats. III. Experimental studies on virus excretion and non-arthropod transmission.

PubMed

Seymour, C; Dickerman, R W

1978-03-01

A total of 80 Neotropical bats of five species was inoculated with one of four strains of Venezuelan encephalitis (VE) virus. Virus was detected in the oropharynges of 56% of bats, and most regularly in Artibeus jamaicensis (75%). Titers of virus in oropharyngeal secretions were occasionally very high (8.5 log10 SMicLD50/ml in one A. jamaicensis). Only 2 of 123 urine samples from 50 bats and 2 of 86 fecal samples from 46 bats yielded VE virus. No contact or aerosol virus transmission from bat to bat was detected. VE virus passed transplacentally from two infected mothers to their fetuses, which were aborted. Virus did not pass from one infected mother to her nursing young.

Zika Virus: History, Emergence, Biology, and Prospects for Control

PubMed Central

Weaver, Scott C.; Costa, Federico; Garcia-Blanco, Mariano A.; Ko, Albert I.; Ribeiro, Guilherme S.; Saade, George; Shi, Pei-Yong; Vasilakis, Nikos

2016-01-01

Zika virus (ZIKV), a previously obscure flavivirus closely related to dengue, West Nile, Japanese encephalitis and yellow fever viruses, has emerged explosively since 2007 to cause a series of epidemics in Micronesia, the South Pacific, and most recently the Americas. After its putative evolution in sub-Saharan Africa, ZIKV spread in the distant past to Asia and has probably emerged on multiple occasions into urban transmission cycles involving Aedes (Stegomyia) spp. mosquitoes and human amplification hosts, accompanied by a relatively mild dengue-like illness. The unprecedented numbers of people infected during recent outbreaks in the South Pacific and the Americas may have resulted in enough ZIKV infections to notice relatively rare congenital microcephaly and Guillain–Barré syndromes. Another hypothesis is that phenotypic changes in Asian lineage ZIKV strains led to these disease outcomes. Here, we review potential strategies to control the ongoing outbreak through vector-centric approaches as well as the prospects for the development of vaccines and therapeutics. PMID:26996139

Zika virus: History, emergence, biology, and prospects for control.

PubMed

Weaver, Scott C; Costa, Federico; Garcia-Blanco, Mariano A; Ko, Albert I; Ribeiro, Guilherme S; Saade, George; Shi, Pei-Yong; Vasilakis, Nikos

2016-06-01

Zika virus (ZIKV), a previously obscure flavivirus closely related to dengue, West Nile, Japanese encephalitis and yellow fever viruses, has emerged explosively since 2007 to cause a series of epidemics in Micronesia, the South Pacific, and most recently the Americas. After its putative evolution in sub-Saharan Africa, ZIKV spread in the distant past to Asia and has probably emerged on multiple occasions into urban transmission cycles involving Aedes (Stegomyia) spp. mosquitoes and human amplification hosts, accompanied by a relatively mild dengue-like illness. The unprecedented numbers of people infected during recent outbreaks in the South Pacific and the Americas may have resulted in enough ZIKV infections to notice relatively rare congenital microcephaly and Guillain-Barré syndromes. Another hypothesis is that phenotypic changes in Asian lineage ZIKV strains led to these disease outcomes. Here, we review potential strategies to control the ongoing outbreak through vector-centric approaches as well as the prospects for the development of vaccines and therapeutics. Copyright © 2016 Elsevier B.V. All rights reserved.

Manipulation of host factors optimizes the pathogenesis of western equine encephalitis virus infections in mice for antiviral drug development.

PubMed

Blakely, Pennelope K; Delekta, Phillip C; Miller, David J; Irani, David N

2015-02-01

While alphaviruses spread naturally via mosquito vectors, some can also be transmitted as aerosols making them potential bioterrorism agents. One such pathogen, western equine encephalitis virus (WEEV), causes fatal human encephalitis via multiple routes of infection and thus presumably via multiple mechanisms. Although WEEV also produces acute encephalitis in non-human primates, a small animal model that recapitulates features of human disease would be useful for both pathogenesis studies and to evaluate candidate antiviral therapies. We have optimized conditions to infect mice with a low passage isolate of WEEV, thereby allowing detailed investigation of virus tropism, replication, neuroinvasion, and neurovirulence. We find that host factors strongly influence disease outcome, and in particular, that age, gender, and genetic background all have significant effects on disease susceptibility independent of virus tropism or replication within the central nervous system. Our data show that experimental variables can be adjusted in mice to recapitulate disease features known to occur in both non-human primates and humans, thus aiding further study of WEEV pathogenesis and providing a realistic therapeutic window for antiviral drug delivery.

Manipulation of host factors optimizes the pathogenesis of western equine encephalitis virus infections in mice for antiviral drug development

PubMed Central

Blakely, Pennelope K.; Delekta, Phillip C.; Miller, David J.; Irani, David N.

2014-01-01

While alphaviruses spread naturally via mosquito vectors, some can also be transmitted as aerosols making them potential bioterrorism agents. One such pathogen, western equine encephalitis virus (WEEV), causes fatal human encephalitis via multiple routes of infection and thus presumably via multiple mechanisms. Although WEEV also produces acute encephalitis in non-human primates, a small animal model that recapitulates features of human disease would be useful for both pathogenesis studies and to evaluate candidate antiviral therapies. We have optimized conditions to infect mice with a low passage isolate of WEEV, thereby allowing detailed investigation of virus tropism, replication, neuroinvasion, and neurovirulence. We find that host factors strongly influence disease outcome, and in particular that age, gender and genetic background all have significant effects on disease susceptibility independent of virus tropism or replication within the central nervous system. Our data show that experimental variables can be adjusted in mice to recapitulate disease features known to occur in both non-human primates and humans, thus aiding further study of WEEV pathogenesis and providing a realistic therapeutic window for antiviral drug delivery. PMID:25361697

Regulation of cell survival and death during Flavivirus infections

PubMed Central

Ghosh Roy, Sounak; Sadigh, Beata; Datan, Emmanuel; Lockshin, Richard A; Zakeri, Zahra

2014-01-01

Flaviviruses, ss(+) RNA viruses, include many of mankind’s most important pathogens. Their pathogenicity derives from their ability to infect many types of cells including neurons, to replicate, and eventually to kill the cells. Flaviviruses can activate tumor necrosis factor α and both intrinsic (Bax-mediated) and extrinsic pathways to apoptosis. Thus they can use many approaches for activating these pathways. Infection can lead to necrosis if viral load is extremely high or to other types of cell death if routes to apoptosis are blocked. Dengue and Japanese Encephalitis Virus can also activate autophagy. In this case the autophagy temporarily spares the infected cell, allowing a longer period of reproduction for the virus, and the autophagy further protects the cell against other stresses such as those caused by reactive oxygen species. Several of the viral proteins have been shown to induce apoptosis or autophagy on their own, independent of the presence of other viral proteins. Given the versatility of these viruses to adapt to and manipulate the metabolism, and thus to control the survival of, the infected cells, we need to understand much better how the specific viral proteins affect the pathways to apoptosis and autophagy. Only in this manner will we be able to minimize the pathology that they cause. PMID:24921001

Communicable Diseases Network Australia National Arbovirus and Malaria Advisory Committee annual report, 2005-06.

PubMed

Liu, Conan; Johansen, Cheryl; Kurucz, Nina; Whelan, Peter

2006-01-01

This report describes the epidemiology of mosquito-borne disease in Australia for the mosquito-borne disease season 1 July 2005 to 30 June 2006, in which the second largest number of notifications since 1995-96 was reported. Ross River virus (RRV) infections (66%), Barmah Forest virus (BFV) infections (23%) and malaria (9%) were the most common mosquito-borne diseases reported in 2005-06. National RRV notifications were the fifth largest on record. The Northern Territory had the highest rate of RRV notifications and the peak notification rate (in January 2006) was the third highest since 2000. National BFV notification rates were the highest on record. The Northern Territory also reported the highest BFV notification rate this season, peaking in February-March 2006, which was the highest reported BFV notification rate on record. BFV notification rates were significantly higher in teenagers compared to previous seasons. There were 731 notifications of malaria in 2005-06 of which none was reported as locally acquired. This was the third highest reporting period for malaria notifications since 2000. In contrast to previous years in which Plasmodium vivax was the predominant species, Plasmodium falciparum was reported as the infecting species in 45 per cent of the malaria notifications and Plasmodium vivax for 42 per cent of cases. Young adults in the 20-24 year age group had the highest number of cases and children in the 5-9 year age group accounted for 22 per cent of notifications. There were two cases of Kunjin virus (KUNV) infection and one case of Murray Valley encephalitis virus (MVEV) infection reported in 2005-06, all from Western Australia. Sentinel chicken surveillance data for flaviviruses and sentinel pig surveillance data for Japanese encephalitis virus are reported. There were 200 notifications of dengue virus (DENV) infection in 2005-06, of which 46 per cent (n = 92) was reported as having been acquired overseas. Dengue serotypes 2 and 3 were detected in two outbreaks of locally-acquired dengue in Queensland this season.

Vector Competence of New Zealand Mosquitoes for Selected Arboviruses

PubMed Central

Kramer, Laura D.; Chin, Pam; Cane, Rachel P.; Kauffman, Elizabeth B.; Mackereth, Graham

2011-01-01

New Zealand (NZ) historically has been free of arboviral activity with the exception of Whataroa virus (Togaviridae: Alphavirus), which is established in bird populations and is transmitted by local mosquitoes. This naive situation is threatened by global warming, invasive mosquitoes, and tourism. To determine the threat of selected medically important arboviruses to NZ, vector competence assays were conducted using field collected endemic and introduced mosquito species. Four alphaviruses (Togaviridae): Barmah Forest virus, Chikungunya virus, Ross River virus, and Sindbis virus, and five flaviviruses (Flaviviridae): Dengue virus 2, Japanese encephalitis virus, Murray Valley encephalitis virus, West Nile virus, and Yellow fever virus were evaluated. Results indicate some NZ mosquito species are highly competent vectors of selected arboviruses, particularly alphaviruses, and may pose a threat were one of these arboviruses introduced at a time when the vector was prevalent and the climatic conditions favorable for virus transmission. PMID:21734146

Japanese Encephalitis: Frequently Asked Questions

MedlinePlus

... the vaccine, what should I do? What is Japanese encephalitis? Japanese encephalitis (JE) is a potentially severe ... cause inflammation of the brain (encephalitis). Where does Japanese encephalitis occur? JE occurs in Asia and parts ...

Evaluation of a caprine arthritis-encephalitis virus/maedi-visna virus indirect enzyme-linked immunosorbent assay in the serological diagnosis of ovine progressive pneumonia virus in U.S. sheep

USDA-ARS?s Scientific Manuscript database

Serological diagnostic testing of sheep and goats using enzyme immunosorbent assays (ELISAs) is the most common method of determining small ruminant lentivirus (SRLV) infection. A caprine arthritis-encephalitis virus (CAEV)/maedi-visna virus (MVV) indirect (i) ELISA, which utilizes MVV EV1 capsid a...

Comparison of PanBio Dengue Duo Enzyme-Linked Immunosorbent Assay (ELISA) and MRL Dengue Fever Virus Immunoglobulin M Capture ELISA for Diagnosis of Dengue Virus Infections in Southeast Asia

PubMed Central

Cuzzubbo, Andrea J.; Vaughn, David W.; Nisalak, Ananda; Solomon, Tom; Kalayanarooj, Siripen; Aaskov, John; Dung, Nguyen Minh; Devine, Peter L.

1999-01-01

The performances of the MRL dengue fever virus immunoglobulin M (IgM) capture enzyme-linked immunosorbent assay (ELISA) and the PanBio Dengue Duo IgM capture and IgG capture ELISA were compared. Eighty sera from patients with dengue virus infections, 24 sera from patients with Japanese encephalitis (JE), and 78 sera from patients with nonflavivirus infections, such as malaria, typhoid, leptospirosis, and scrub typhus, were used. The MRL test showed superior sensitivity for dengue virus infections (94 versus 89%), while the PanBio test showed superior specificity for JE (79 versus 25%) and other infections (100 versus 91%). The PanBio ELISA showed better overall performance, as assessed by the sum of sensitivity and specificity (F value). When dengue virus and nonflavivirus infections were compared, F values of 189 and 185 were obtained for the PanBio and MRL tests, respectively, while when dengue virus infections and JE were compared, F values of 168 and 119 were obtained. The results obtained with individual sera in the PanBio and MRL IgM ELISAs showed good correlation, but this analysis revealed that the cutoff value of the MRL test was set well below that of the PanBio test. Comparing the sensitivity and specificity of the tests at different cutoff values (receiver-operator analysis) revealed that the MRL and PanBio IgM ELISAs performed similarly in distinguishing dengue virus from nonflavivirus infections, although the PanBio IgM ELISA showed significantly better distinction between dengue virus infections and JE. The implications of these findings for the laboratory diagnosis of dengue are discussed. PMID:10473522

Serologic diagnosis of West Nile and St. Louis encephalitis virus infections in domestic chickens.

PubMed

Patiris, Peter J; Oceguera, Leopoldo F; Peck, George W; Chiles, Robert E; Reisen, William K; Hanson, Carl V

2008-03-01

Adult domestic chickens were infected with West Nile virus (WNV) or St. Louis encephalitis virus (SLEV) and challenged with homologous or heterologous virus at 21 or 56 days postinfection (dpi). Sera were collected at selected time points after infection and assayed by enzyme immunoassay (EIA), plaque reduction neutralization test (PRNT), and a Western blot (WB) alternative to PRNT. EIA results were sensitive and accurate (few false positives) but not specific, requiring a confirmatory test to determine virus infection history. PRNT results generally were specific until challenge, after which test results were frequently equivocal and inadequate to determine first or second infecting virus. WB results confirmed the serologic cross-reactivity between WNV and SLEV envelope protein. Non-structural protein 1 and pre-membrane protein reactivities were highly specific for WNV during SLEV infection, but less specific for SLEV during WNV infection. WB and PRNT specificities were similar for both viruses from 6 to 14 dpi, and sensitivities to WNV were virtually identical.

West Nile Virus Encephalitis in a Barbary Macaque (Macaca sylvanus)

PubMed Central

Barker, Ian K.; Crawshaw, Graham J.; Bertelsen, Mads F.; Drebot, Michael A.; Andonova, Maya

2004-01-01

An aged Barbary ape (Macaca sylvanus) at the Toronto Zoo became infected with naturally acquired West Nile virus (WNV) encephalitis that caused neurologic signs, which, associated with other medical problems, led to euthanasia. The diagnosis was based on immunohistochemical assay of brain lesions, reverse transcriptase–polymerase chain reaction, and virus isolation. PMID:15200866

Diagnosis of Fatal Human Case of St. Louis Encephalitis Virus Infection by Metagenomic Sequencing, California, 2016.

PubMed

Chiu, Charles Y; Coffey, Lark L; Murkey, Jamie; Symmes, Kelly; Sample, Hannah A; Wilson, Michael R; Naccache, Samia N; Arevalo, Shaun; Somasekar, Sneha; Federman, Scot; Stryke, Doug; Vespa, Paul; Schiller, Gary; Messenger, Sharon; Humphries, Romney; Miller, Steve; Klausner, Jeffrey D

2017-10-01

We used unbiased metagenomic next-generation sequencing to diagnose a fatal case of meningoencephalitis caused by St. Louis encephalitis virus in a patient from California in September 2016. This case is associated with the recent 2015-2016 reemergence of this virus in the southwestern United States.

Distemper virus encephalitis exerts detrimental effects on hippocampal neurogenesis.

PubMed

von Rüden, E-L; Avemary, J; Zellinger, C; Algermissen, D; Bock, P; Beineke, A; Baumgärtner, W; Stein, V M; Tipold, A; Potschka, H

2012-08-01

Despite knowledge about the impact of brain inflammation on hippocampal neurogenesis, data on the influence of virus encephalitis on dentate granule cell neurogenesis are so far limited. Canine distemper is considered an interesting model of virus encephalitis, which can be associated with a chronic progressing disease course and can cause symptomatic seizures. To determine the impact of canine distemper virus (CDV) infection on hippocampal neurogenesis, we compared post-mortem tissue from dogs with infection with and without seizures, from epileptic dogs with non-viral aetiology and from dogs without central nervous system diseases. The majority of animals with infection and with epilepsy of non-viral aetiology exhibited neuronal progenitor numbers below the age average in controls. Virus infection with and without seizures significantly decreased the mean number of neuronal progenitor cells by 43% and 76% as compared to age-matched controls. Ki-67 labelling demonstrated that hippocampal cell proliferation was neither affected by infection nor by epilepsy of non-viral aetiology. Analysis of CDV infection in cells expressing caspase-3, doublecortin or Ki-67 indicated that infection of neuronal progenitor cells is extremely rare and suggests that infection might damage non-differentiated progenitor cells, hamper neuronal differentiation and promote glial differentiation. A high inter-individual variance in the number of lectin-reactive microglial cells was evident in dogs with distemper infection. Statistical analyses did not reveal a correlation between the number of lectin-reactive microglia cells and neuronal progenitor cells. Our data demonstrate that virus encephalitis with and without seizures can exert detrimental effects on hippocampal neurogenesis, which might contribute to long-term consequences of the disease. The lack of a significant impact of distemper virus on Ki-67-labelled cells indicates that the infection affected neuronal differentiation and survival of newborn cells rather than hippocampal cell proliferation. © 2011 The Authors. Neuropathology and Applied Neurobiology © 2011 British Neuropathological Society.

Tick-borne encephalitis virus and the immune response of the mammalian host.

PubMed

Dörrbecker, Bastian; Dobler, Gerhard; Spiegel, Martin; Hufert, Frank T

2010-07-01

Tick-borne encephalitis (TBE) is caused by Tick-borne encephalitis virus (TBEV), one of the most prevalent arboviruses in Europe and in many parts of Asia. Transmission of TBEV to humans usually occurs by bite of an infected tick or rarely by ingestion of unpasteurized milk products of infected livestock. TBEV infection induces an innate and adaptive immune response, nevertheless it is able to replicate in several cell types of the immune system at the same time which probably contributes to the spread of the virus in the human host. Furthermore, TBEV can enter the central nervous system (CNS) by yet not well understood mechanisms via the blood brain barrier (BBB) or the olfactory neurons which leads to serious neurological disorders like meningitis, encephalitis or even meningoencephalitis. In this article we review the known facts and possible hypotheses of interaction of TBEV with components of the mammalian immune system and their implications for TBEV-mediated pathogenesis. Copyright © 2010 Elsevier Ltd. All rights reserved.

Breast milk transmission of flaviviruses in the context of Zika virus: A systematic review.

PubMed

Mann, Taylor Z; Haddad, Lisa B; Williams, Tonya R; Hills, Susan L; Read, Jennifer S; Dee, Deborah L; Dziuban, Eric J; Pérez-Padilla, Janice; Jamieson, Denise J; Honein, Margaret A; Shapiro-Mendoza, Carrie K

2018-06-08

Since the Zika virus epidemic in the Americas began in 2015, Zika virus transmission has occurred throughout the Americas. However, limited information exists regarding possible risks of transmission of Zika virus and other flaviviruses through breast feeding and human milk. We conducted a systematic review of the evidence regarding flaviviruses detection in and transmission through milk, specifically regarding Zika virus, Japanese encephalitis virus, tick-borne encephalitis virus, Powassan virus, West Nile virus, dengue virus, and yellow fever virus. Medline, Embase, Global Health, CINAHL, Cochrane Library, Scopus, Popline, Virtual Health Library, and WorldCat were searched through June 2017. Two authors independently screened potential studies for inclusion and extracted data. Human and nonhuman (animal) studies describing: 1) confirmed or suspected cases of mother-to-child transmission through milk; or 2) the presence of flavivirus genomic material in milk. Seventeen studies were included, four animal models and thirteen observational studies. Dengue virus, West Nile virus, and Zika virus viral ribonucleic acid was detected in human milk, including infectious Zika virus and dengue virus viral particles. Human breast-feeding transmission was confirmed for only yellow fever virus. There was evidence of milk-related transmission of dengue virus, Powassan virus, and West Nile virus in animal studies. Because the health advantages of breast feeding are considered greater than the potential risk of transmission, the World Health Organization recommends that mothers with possible or confirmed Zika virus infection or exposure continue to breast feed. This review did not identify any data that might alter this recommendation. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.

Japanese encephalitis in a 114-month-old cow: pathological investigation of the affected cow and genetic characterization of Japanese encephalitis virus isolate.

PubMed

Kako, Naomi; Suzuki, Seiji; Sugie, Norie; Kato, Tomoko; Yanase, Tohru; Yamakawa, Makoto; Shirafuji, Hiroaki

2014-03-11

Japanese encephalitis virus (JEV) is classified into the genus Flavivirus in the family Flaviviridae. JEV can cause febrile illness and encephalitis mainly in humans and horses, and occasionally in cattle. In late September 2010, a 114-month-old cow showed neurological symptoms similar to the symptoms observed in previous bovine cases of Japanese encephalitis (JE); therefore, we conducted virological and pathological tests on the cow. As a result, JEV was isolated from the cerebrum of the affected cow. We determined the complete genome sequence of the JEV isolate, which we named JEV/Bo/Aichi/1/2010, including the envelope (E) gene region and 3' untranslated region (3'UTR). Our phylogenetic analyses of the E region and complete genome showed that the isolate belongs to JEV genotype 1 (G1). The isolate, JEV/Bo/Aichi/1/2010, was most closely related to several JEV G1 isolates in Toyama Prefecture, Japan in 2007-2009 by the phylogenetic analysis of the E region. In addition, the nucleotide alignment revealed that the deletion in the 3'UTR was the same between JEV/Bo/Aichi/1/2010 and several other JEV G1 isolates identified in Toyama Prefecture in 2008-2009. A hemagglutination inhibition (HI) test was conducted for the detection of anti-JEV antibodies in the affected cow, and the test detected 2-mercaptoethanol (2-ME)-sensitive HI antibodies against JEV in the serum of the affected cow. The histopathological investigation revealed nonsuppurative encephalomyelitis in the affected cow, and the immunohistochemical assay detected JEV antigen in the cerebrum. We diagnosed the case as JE of a cow based on the findings of nonsuppurative encephalomyelitis observed in the central nervous system, JEV antigen detected in the cerebrum, JEV isolated from the cerebrum, and 2-ME-sensitive HI antibodies against JEV detected in the serum. This is the first reported case of JE in a cow over 24 months old.

Three-dimensional morphometric analysis of microglial changes in a mouse model of virus encephalitis: age and environmental influences.

PubMed

de Sousa, Aline A; Dos Reis, Renata R; de Lima, Camila M; de Oliveira, Marcus A; Fernandes, Taiany N; Gomes, Giovanni F; Diniz, Daniel G; Magalhães, Nara M; Diniz, Cristovam G; Sosthenes, Marcia C K; Bento-Torres, João; Diniz, José Antonio P; Vasconcelos, Pedro F da C; Diniz, Cristovam Wanderley P

2015-08-01

Many RNA virus CNS infections cause neurological disease. Because Piry virus has a limited human pathogenicity and exercise reduces activation of microglia in aged mice, possible influences of environment and aging on microglial morphology and behavior in mice sublethal encephalitis were investigated. Female albino Swiss mice were raised either in standard (S) or in enriched (EE) cages from age 2 to 6 months (young - Y), or from 2 to 16 months (aged - A). After behavioral tests, mice nostrils were instilled with Piry-virus-infected or with normal brain homogenates. Brain sections were immunolabeled for virus antigens or microglia at 8 days post-infection (dpi), when behavioral changes became apparent, and at 20 and 40 dpi, after additional behavioral testing. Young infected mice from standard (SYPy) and enriched (EYPy) groups showed similar transient impairment in burrowing activity and olfactory discrimination, whereas aged infected mice from both environments (EAPy, SAPy) showed permanent reduction in both tasks. The beneficial effects of an enriched environment were smaller in aged than in young mice. Six-hundred and forty microglial cells, 80 from each group were reconstructed. An unbiased, stereological sampling approach and multivariate statistical analysis were used to search for microglial morphological families. This procedure allowed distinguishing between microglial morphology of infected and control subjects. More severe virus-associated microglial changes were observed in young than in aged mice, and EYPy seem to recover microglial homeostatic morphology earlier than SYPy . Because Piry-virus encephalitis outcomes were more severe in aged mice, it is suggested that the reduced inflammatory response in those individuals may aggravate encephalitis outcomes. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

A review of West Nile and Usutu virus co-circulation in Europe: how much do transmission cycles overlap?

PubMed

Nikolay, Birgit

2015-10-01

Due to the increasing global spread of arboviruses, the geographic extent of virus co-circulation is expanding. This complicates the diagnosis of febrile conditions and can have direct effects on the epidemiology. As previously demonstrated, subsequent infections by two closely related viruses, such as those belonging to the Japanese encephalitis virus (JEV) serocomplex, can lead to partial or complete cross-immunity, altering the risk of infections or the outcome of disease. Two flaviviruses that may interact at population level are West Nile virus (WNV) and Usutu virus (USUV). These pathogens have antigenic cross-reactivity and affect human and animal populations throughout Europe. This systematic review investigates the overlap of WNV and USUV transmission cycles, not only geographically but also in terms of host and vector ranges. Co-circulation of WNV and USUV was reported in 10 countries and the viruses were found to infect 34 common bird species belonging to 11 orders. Moreover, four mosquito species are potential vectors for both viruses. Taken together, these data suggest that WNV and USUV transmission overlaps substantially in Europe and highlight the importance of further studies investigating the interactions between the two viruses within host and vector populations. © The Author 2015. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Phylogeography of Japanese Encephalitis Virus: Genotype Is Associated with Climate

PubMed Central

Schuh, Amy J.; Ward, Melissa J.; Leigh Brown, Andrew J.; Barrett, Alan D. T.

2013-01-01

The circulation of vector-borne zoonotic viruses is largely determined by the overlap in the geographical distributions of virus-competent vectors and reservoir hosts. What is less clear are the factors influencing the distribution of virus-specific lineages. Japanese encephalitis virus (JEV) is the most important etiologic agent of epidemic encephalitis worldwide, and is primarily maintained between vertebrate reservoir hosts (avian and swine) and culicine mosquitoes. There are five genotypes of JEV: GI-V. In recent years, GI has displaced GIII as the dominant JEV genotype and GV has re-emerged after almost 60 years of undetected virus circulation. JEV is found throughout most of Asia, extending from maritime Siberia in the north to Australia in the south, and as far as Pakistan to the west and Saipan to the east. Transmission of JEV in temperate zones is epidemic with the majority of cases occurring in summer months, while transmission in tropical zones is endemic and occurs year-round at lower rates. To test the hypothesis that viruses circulating in these two geographical zones are genetically distinct, we applied Bayesian phylogeographic, categorical data analysis and phylogeny-trait association test techniques to the largest JEV dataset compiled to date, representing the envelope (E) gene of 487 isolates collected from 12 countries over 75 years. We demonstrated that GIII and the recently emerged GI-b are temperate genotypes likely maintained year-round in northern latitudes, while GI-a and GII are tropical genotypes likely maintained primarily through mosquito-avian and mosquito-swine transmission cycles. This study represents a new paradigm directly linking viral molecular evolution and climate. PMID:24009790

Phylogeography of Japanese encephalitis virus: genotype is associated with climate.

PubMed

Schuh, Amy J; Ward, Melissa J; Brown, Andrew J Leigh; Barrett, Alan D T

2013-01-01

The circulation of vector-borne zoonotic viruses is largely determined by the overlap in the geographical distributions of virus-competent vectors and reservoir hosts. What is less clear are the factors influencing the distribution of virus-specific lineages. Japanese encephalitis virus (JEV) is the most important etiologic agent of epidemic encephalitis worldwide, and is primarily maintained between vertebrate reservoir hosts (avian and swine) and culicine mosquitoes. There are five genotypes of JEV: GI-V. In recent years, GI has displaced GIII as the dominant JEV genotype and GV has re-emerged after almost 60 years of undetected virus circulation. JEV is found throughout most of Asia, extending from maritime Siberia in the north to Australia in the south, and as far as Pakistan to the west and Saipan to the east. Transmission of JEV in temperate zones is epidemic with the majority of cases occurring in summer months, while transmission in tropical zones is endemic and occurs year-round at lower rates. To test the hypothesis that viruses circulating in these two geographical zones are genetically distinct, we applied Bayesian phylogeographic, categorical data analysis and phylogeny-trait association test techniques to the largest JEV dataset compiled to date, representing the envelope (E) gene of 487 isolates collected from 12 countries over 75 years. We demonstrated that GIII and the recently emerged GI-b are temperate genotypes likely maintained year-round in northern latitudes, while GI-a and GII are tropical genotypes likely maintained primarily through mosquito-avian and mosquito-swine transmission cycles. This study represents a new paradigm directly linking viral molecular evolution and climate.

West Nile virus infection.

PubMed

Guharoy, Roy; Gilroy, Shelley A; Noviasky, John A; Ference, Jonathan

2004-06-15

The epidemiology, virology, and transmission of West Nile virus (WNV) are reviewed, and the clinical features, diagnosis, and treatment of WNV infection are examined. WNV infection is caused by a flavivirus transmitted from birds to humans through the bite of culicine mosquitoes. WNV was discovered in the blood of a febrile woman from Uganda's West Nile province in 1937. The first case of domestically acquired WNV infection was reported in the United States in 1999 in New York. Since then, WNV infection has spread rapidly across the United States, with 9306 confirmed cases and 210 deaths reported from 45 states in 2003. It is still not clear how WNV was introduced into North America. WNV is a small, single-stranded RNA virus and a member of the Japanese encephalitis virus antigenic complex. While most humans infected with WNV are asymptomatic, some may develop an influenza-like illness. Disease surveillance remains the cornerstone for the early recognition and control of WNV. We describe one case of WNV infection with an update on the disease. Strategies for the prevention and control of this infection are reviewed. There is no established treatment for WNV infection. Currently, prevention and control are the only measures that help decrease the morbidity and mortality associated with WNV infection. As the number of cases escalates and the geographic distribution of WNV infection widens, the epidemic will continue to pose a major challenge to clinicians in the coming years. There is an urgent need for more research on the pathogenesis and treatment of WNV infection.

Experimental Transmission of Eastern Equine Encephalitis Virus by Strains of Aedes albopictus and A. taeniorhynchus (Diptera: Culicidae)

DTIC Science & Technology

1994-01-01

AD-A281 335 0 Experimental Transmission of Eastern Equine Encephaliti Vi 4 by Strains of Aedes albopictus and A. taeniorhynch &1j (Diptera: Culicidae...co m •strains of Aedes albopictus (Skuse) was assessed for eastern equine encephalitis (EEE) virus isolated from Ae. albopictus collected in Polk...County, Florida. Both species became infected with and transmitted EEE virus by bite after feeding on 1-d-old chicks that had _been inoculated with EEE

Comparison of immune responses of brown-headed cowbird and related blackbirds to West Nile and other mosquito-borne encephalitis viruses

USGS Publications Warehouse

Reisen, W.K.; Hahn, D.C.

2007-01-01

The rapid geographic spread of West Nile virus (family Flaviviridae, genus Flavivirus, WNV) across the United States has stimulated interest in comparative host infection studies to delineate competent avian hosts critical for viral amplification. We compared the host competence of four taxonomically related blackbird species (Icteridae) after experimental infection with WNV and with two endemic, mosquito-borne encephalitis viruses, western equine encephalomyelitis virus (family Togaviridae, genus Alphavirus, WEEV), and St, Louis encephalitis virus (family Flaviviridae, genus Flavivirus, SLEV). We predicted differences in disease resistance among the blackbird species based on differences in life history, because they differ in geographic range and life history traits that include mating and breeding systems. Differences were observed among the response of these hosts to all three viruses, Red-winged Blackbirds were more susceptible to SLEV than Brewer's Blackbirds, whereas Brewer's Blackbirds were more susceptible to WEEV than Red-winged Blackbirds. In response to WNV infection, cowbirds showed the lowest mean viremias, cleared their infections faster, and showed lower antibody levels than concurrently infected species. Brown-headed Cowbirds also exhibited significantly lower viremia responses after infection with SLEV and WEEV as well as coinfection with WEEV and WNV than concurrently infected icterids. We concluded that cowbirds may be more resistant to infection to both native and introduced viruses because they experience heightened exposure to a variety of pathogens of parenting birds during the course of their parasitic life style.

Comparison of immune responses of brown-headed cowbird and related blackbirds to west Nile and other mosquito-borne encephalitis viruses.

PubMed

Reisen, William K; Hahn, D Caldwell

2007-07-01

The rapid geographic spread of West Nile virus (family Flaviviridae, genus Flavivirus, WNV) across the United States has stimulated interest in comparative host infection studies to delineate competent avian hosts critical for viral amplification. We compared the host competence of four taxonomically related blackbird species (Icteridae) after experimental infection with WNV and with two endemic, mosquito-borne encephalitis viruses, western equine encephalomyelitis virus (family Togaviridae, genus Alphavirus, WEEV), and St. Louis encephalitis virus (family Flaviviridae, genus Flavivirus, SLEV). We predicted differences in disease resistance among the blackbird species based on differences in life history, because they differ in geographic range and life history traits that include mating and breeding systems. Differences were observed among the response of these hosts to all three viruses. Red-winged Blackbirds were more susceptible to SLEV than Brewer's Blackbirds, whereas Brewer's Blackbirds were more susceptible to WEEV than Red-winged Blackbirds. In response to WNV infection, cowbirds showed the lowest mean viremias, cleared their infections faster, and showed lower antibody levels than concurrently infected species. Brown-headed Cowbirds also exhibited significantly lower viremia responses after infection with SLEV and WEEV as well as coinfection with WEEV and WNV than concurrently infected icterids. We concluded that cowbirds may be more resistant to infection to both native and introduced viruses because they experience heightened exposure to a variety of pathogens of parenting birds during the course of their parasitic life style.

West nile virus disease and other arboviral diseases - United States, 2011.

PubMed

2012-07-13

Arthropodborne viruses (arboviruses) are transmitted to humans primarily through the bites of infected mosquitoes and ticks. Symptomatic infections most often manifest as a systemic febrile illness and, less commonly, as neuroinvasive disease (e.g., meningitis, encephalitis, or acute flaccid paralysis). West Nile virus (WNV) is the leading cause of domestically acquired arboviral disease in the United States. However, several other arboviruses also cause seasonal outbreaks and sporadic cases. In 2011, CDC received reports of 871 cases of nationally notifiable arboviral diseases (excluding dengue); etiological agents included WNV (712 cases), La Crosse virus (LACV) (130), Powassan virus (POWV) (16), St. Louis encephalitis virus (SLEV) (six), Eastern equine encephalitis virus (EEEV) (four), and Jamestown Canyon virus (JCV) (three). Of these, 624 (72%) were classified as neuroinvasive disease, for a national incidence of 0.20 per 100,000 population. WNV and other arboviruses continue to cause focal outbreaks and severe illness in substantial numbers of persons in the United States.

The rationale for integrated childhood meningoencephalitis surveillance: a case study from Cambodia

PubMed Central

Touch, Sok; Hills, Susan; Rani, Manju; Samnang, Chham; Khalakdina, Asheena; Jacobson, Julie

2009-01-01

Abstract Problem Recent progress in vaccine availability and affordability has raised prospects for reducing death and disability from neurological infections in children. In many Asian countries, however, the epidemiology and public health burden of neurological diseases such as Japanese encephalitis and bacterial meningitis are poorly understood. Approach A sentinel surveillance system for Japanese encephalitis was developed and embedded within the routine meningoencephalitis syndromic surveillance system in Cambodia in 2006. The sentinel surveillance system was designed so surveillance and laboratory testing for other etiologies of neurological infection could be incorporated. Local setting The Communicable Disease Control department of the Ministry of Health in Cambodia worked with partners to establish the sentinel surveillance system. Relevant changes The sentinel surveillance system has provided important information on the disease burden of Japanese encephalitis in Cambodia and is now providing a platform for expansion to incorporate laboratory testing for other vaccine-preventable neurological infections in children. Lessons learned Sentinel surveillance systems, when linked to syndromic reporting systems, can characterize the epidemiology of meningoencephalitis and identify the proportion of hospital-based neurological infection in children that is vaccine preventable. Integrated systems enable consistency in data collection, analysis and information dissemination, and they enhance the capacity of public health managers to provide more credible and integrated information to policy-makers. This will assist decision-making about the potential role of immunization in reducing the incidence of childhood neurological infections. PMID:19551241

Proposal for Japanese encephalitis surveillance using captured invasive mongooses under an eradication project on Okinawa Island, Japan.

PubMed

Saito, Mika; Nakata, Katsushi; Nishijima, Taku; Yamashita, Katsuhiro; Saito, Anna; Ogura, Go

2009-06-01

A project to eradicate invasive small Asian mongooses (Herpestes javanicus) is underway to conserve the unique ecosystem of Okinawa Island, Japan. In the present study, we tried to elucidate whether the mongoose is a host of Japanese encephalitis virus (JEV) and to evaluate the reliability of surveillance of Japanese encephalitis (JE) using this species. Culex tritaeniorhynchus, the main vector mosquito of JEV, feeds on the mongoose. Eighty-five (35.4%) of 240 wild small Asian mongooses captured between 2001 and 2005 had neutralizing antibodies against more than one of four JEV strains. Prevalence rates of JEV antibodies tended to increase with body weight and length of the animals. One of three sentinel mongooses showed a temporal change in antibody titer. These results indicate that the small Asian mongooses on Okinawa Island are sensitive to JEV. From the antibody titers and the locations of capture, the JEV active area was clarified. We propose that surveillance of JE using mongooses captured under the eradication program is reliable.

Powassan encephalitis and Colorado tick fever.

PubMed

Romero, José R; Simonsen, Kari A

2008-09-01

This article discusses two tick-borne illnesses: Powassan encephalitis, a rare cause of central nervous system infection caused by the Powassan virus, and Colorado tick fever, an acute febrile illness caused by the Colorado tick fever virus common to the Rocky Mountain region of North America.

[Meningitis and encephalitis in Poland in 2010].

PubMed

Parda, Natalia; Polkowska, Aleksandra

2012-01-01

Annually 2 000-3 000 cases of meningitis and encephalitis are notified to the Polish surveillance system. The leading etiologic agents of the bacterial infections are: N. meningitidis, S. pneumoniae, H. influenzae type B and L. monocytogenes. The most common causes of bacterial infections in children are: E. coli, S. agalactiae and H. influenzae type B. The viral infections are mainly caused by the following pathogens: Echovirus, Coxsackie virus group A and B. The agents responsible for the viral infections are also: arboviruses, Herpes simplex virus and mumps virus. The objectives of the present article are to analyze the epidemiology of meningitis and encephalitis in Poland in 2010 and to present the information on the vaccines used to prevent the discussed infections. The analysis was based on the data retrieved from the questionnaires used for the surveillance purposes, aggregated data on meningitis and encephalitis published in "Infectious diseases and poisonings in Poland in 2010", aggregated data on the vaccination coverage published in "Vaccinations in Poland in 2010", "Case definitions for the infectious diseases used for the surveillance purposes in 2009-2011" and Polish Immunization Programme for 2010. In 2010, Poland reported 3 063 neuroinfections--nearly 22% more than in 2009. The incidence rate was 8.03 cases per 100 000 population. From the analysis of data transpired that of the notified cases, 1 619 were of viral etiology, 846--were bacterial and 598 of other or unknown origin. Given the bacterial infections of determined etiology, the leading pathogenic agent was S. pneumoniae (180 cases), following by N. meningitidis (146 cases) and Haemophilus influenzae typu B (11 cases). Among confirmed cases of the viral infections, the predominant were tick-borne encephalitis cases (294). Compared to the data from 2009, the epidemiologic situation of the meningitis and encephalitis in Poland in 2010 has not changed significantly.

Recombinant vaccinia/Venezuelan equine encephalitis (VEE) virus expresses VEE structural proteins.

PubMed

Kinney, R M; Esposito, J J; Johnson, B J; Roehrig, J T; Mathews, J H; Barrett, A D; Trent, D W

1988-12-01

cDNA molecules encoding the structural proteins of the virulent Trinidad donkey and the TC-83 vaccine strains of Venezuelan equine encephalitis (VEE) virus were inserted under control of the vaccinia virus 7.5K promoter into the thymidine kinase gene of vaccinia virus. Synthesis of the capsid protein and glycoproteins E2 and E1 of VEE virus was demonstrated by immunoblotting of lysates of CV-1 cells infected with recombinant vaccinia/VEE viruses. VEE glycoproteins were detected in recombinant virus-infected cells by fluorescent antibody (FA) analysis performed with a panel of VEE-specific monoclonal antibodies. Seven E2-specific epitopes and two of four E1-specific epitopes were demonstrated by FA.

Powassan virus infection: case series and literature review from a single institution

PubMed Central

2012-01-01

Background Powassan virus is a flavivirus related to eastern hemisphere’s tick-borne encephalitis viruses. It can cause a rare but potentially life-threatening disease including encephalitis. Case presentation We report four cases of POWV infection in Minnesota and North Dakota with known exposure to tick bites in 2011. Our first case was an 18-year-old male who dramatically presented with seizure and headache with positive serum analysis for Powassan virus immunoglobulin M. The second case was a 60 year old gentleman with intraparenchymal hemorrhage and was diagnosed via cerebrospinal fluid analysis. Thirdly, a 61 year old male developed altered mental status and encephalitis. Our fourth patient was a 69 year old male who had headache and non-focal weakness who was diagnosed with serum analysis. Conclusion Symptoms of Powassan virus infection ranged from headaches to seizures and severe neurological symptoms. This study serves to highlight the increased detection of Powassan virus infection in the central north United States. This report focuses on the increasing incidence that can lead to increasing efforts for raising awareness regarding this infection. There is a need for clinician vigilance and public attention due to its increasing detection, westward progression and varied clinical presentations. PMID:23111001

Herpes simplex virus type 1 encephalitis and unusual retinitis in a patient with systemic lupus erythematosus.

PubMed

Zhang, L; Liu, J J; Li, M T

2013-11-01

In this report we discuss a case of a patient with systemic lupus erythematosus who developed herpes simplex virus type 1(HSV-1) infection presenting with encephalitis as well as necrotic and non-necrotic retinitis. The patient presented with typical clinical symptoms and radiologic abnormalities consistent with HSV-1 encephalitis and HSV-1 retinitis in patients with HIV infection, but lacked cerebrospinal fluid pleocytosis and had bilateral retinitis with poor visual acuity. To the best of our knowledge, this is the first such case reported in the literature.

Naloxone-induced seizures in rats infected with Borna disease virus.

PubMed

Solbrig, M V; Koob, G F; Lipkin, W I

1996-04-01

The opioid antagonist naloxone is widely used in the emergency treatment of nontraumatic coma. Although it is uncommon for serious side effects to result from administration of opiate antagonists, we report that naloxone can have epileptogenic effects in the context of encephalitis. In an experimental model of viral encephalitis, rats infected with Borna disease virus developed myoclonic, generalized clonic, or atonic seizures; behavior arrest; and staring spells when treated with naloxone. These findings suggest a novel neuropharmacologic link, through opioid peptide systems, between epilepsy and encephalitis and disclose a potential contraindication to use of opioid antagonists in nontraumatic coma.

Detection of Japanese encephalitis virus genotype V in Culex orientalis and Culex pipiens (Diptera: Culicidae) in Korea.

PubMed

Kim, Hyunwoo; Cha, Go-Woon; Jeong, Young Eui; Lee, Wook-Gyo; Chang, Kyu Sik; Roh, Jong Yul; Yang, Sung Chan; Park, Mi Yeoun; Park, Chan; Shin, E-Hyun

2015-01-01

Japanese encephalitis virus (JEV) causes significant viral encephalitis and is distributed throughout the Asian countries. The virus is known to be transmitted by Culex tritaeniorhynchus, which mainly breeds in rice paddies in Korea. In this study, we investigated the presence of other mosquito species that can transmit JEV as a second or regional vector. We selected five cities where patients have experienced JE in the last 5 years as mosquito-collecting locations and subdivided them into four collection sites according to the mosquito habitats (cowshed, downtown area, forest, and swamp). Mosquitoes were caught using the BG-Sentinel trap, CDC black-light trap, Fay-Prince trap, and Gravid trap. A total of 993 pools from 22,774 mosquitoes were prepared according to their species, collection date, and site. We performed a SYBR Green 1-based real-time RT-PCR assay to detect JEV from the mosquito pools. A total of six JEV-positive pools were detected from Culex orientalis and Culex pipiens caught in the Gangwon-do and Gyeonngi-do provinces. All the detected JEVs were revealed as genotype V by phylogenetic analysis of the envelope gene. Our findings confirm that a new genotype of JEV was introduced in Korea and suggest that two mosquito species may play a role in JEV transmission.

Japanese Encephalitis Surveillance and Immunization - Asia and Western Pacific Regions, 2016.

PubMed

Heffelfinger, James D; Li, Xi; Batmunkh, Nyambat; Grabovac, Varja; Diorditsa, Sergey; Liyanage, Jayantha B; Pattamadilok, Sirima; Bahl, Sunil; Vannice, Kirsten S; Hyde, Terri B; Chu, Susan Y; Fox, Kimberley K; Hills, Susan L; Marfin, Anthony A

2017-06-09

Japanese encephalitis (JE) virus is the most important vaccine-preventable cause of encephalitis in the Asia-Pacific region. The World Health Organization (WHO) recommends integration of JE vaccination into national immunization schedules in all areas where the disease is a public health priority (1). This report updates a previous summary of JE surveillance and immunization programs in Asia and the Western Pacific in 2012 (2). Since 2012, funding for JE immunization has become available through the GAVI Alliance, three JE vaccines have been WHO-prequalified,* and an updated WHO JE vaccine position paper providing guidance on JE vaccines and vaccination strategies has been published (1). Data for this report were obtained from a survey of JE surveillance and immunization practices administered to health officials in countries with JE virus transmission risk, the 2015 WHO/United Nations Children's Fund Joint Reporting Form on Immunization, notes and reports from JE meetings held during 2014-2016, published literature, and websites. In 2016, 22 (92%) of 24 countries with JE virus transmission risk conducted JE surveillance, an increase from 18 (75%) countries in 2012, and 12 (50%) countries had a JE immunization program, compared with 11 (46%) countries in 2012. Strengthened JE surveillance, continued commitment, and adequate resources for JE vaccination should help maintain progress toward prevention and control of JE.

Zika Virus Antagonizes Type I Interferon Responses during Infection of Human Dendritic Cells

PubMed Central

Maddur, Mohan S.; O’Neal, Justin T.; Fedorova, Nadia B.; Puri, Vinita; Pulendran, Bali; Suthar, Mehul S.

2017-01-01

Zika virus (ZIKV) is an emerging mosquito-borne flavivirus that is causally linked to severe neonatal birth defects, including microcephaly, and is associated with Guillain-Barre syndrome in adults. Dendritic cells (DCs) are an important cell type during infection by multiple mosquito-borne flaviviruses, including dengue virus, West Nile virus, Japanese encephalitis virus, and yellow fever virus. Despite this, the interplay between ZIKV and DCs remains poorly defined. Here, we found human DCs supported productive infection by a contemporary Puerto Rican isolate with considerable variability in viral replication, but not viral binding, between DCs from different donors. Historic isolates from Africa and Asia also infected DCs with distinct viral replication kinetics between strains. African lineage viruses displayed more rapid replication kinetics and infection magnitude as compared to Asian lineage viruses, and uniquely induced cell death. Infection of DCs with both contemporary and historic ZIKV isolates led to minimal up-regulation of T cell co-stimulatory and MHC molecules, along with limited secretion of inflammatory cytokines. Inhibition of type I interferon (IFN) protein translation was observed during ZIKV infection, despite strong induction at the RNA transcript level and up-regulation of other host antiviral proteins. Treatment of human DCs with RIG-I agonist potently restricted ZIKV replication, while type I IFN had only modest effects. Mechanistically, we found all strains of ZIKV antagonized type I IFN-mediated phosphorylation of STAT1 and STAT2. Combined, our findings show that ZIKV subverts DC immunogenicity during infection, in part through evasion of type I IFN responses, but that the RLR signaling pathway is still capable of inducing an antiviral state, and therefore may serve as an antiviral therapeutic target. PMID:28152048

Influence of the CCR-5/MIP-1 α Axis in the Pathogenesis of Rocio Virus Encephalitis in a Mouse Model

PubMed Central

Chávez, Juliana H.; França, Rafael F. O.; Oliveira, Carlo J. F.; de Aquino, Maria T. P.; Farias, Kleber J. S.; Machado, Paula R. L.; de Oliveira, Thelma F. M.; Yokosawa, Jonny; Soares, Edson G.; da Silva, João S.; da Fonseca, Benedito A. L.; Figueiredo, Luiz T. M.

2013-01-01

Rocio virus (ROCV) caused an outbreak of human encephalitis during the 1970s in Brazil and its immunopathogenesis remains poorly understood. CC-chemokine receptor 5 (CCR5) is a chemokine receptor that binds to macrophage inflammatory protein (MIP-1 α). Both molecules are associated with inflammatory cells migration during infections. In this study, we demonstrated the importance of the CCR5 and MIP-1 α, in the outcome of viral encephalitis of ROCV-infected mice. CCR5 and MIP-1 α knockout mice survived longer than wild-type (WT) ROCV-infected animals. In addition, knockout mice had reduced inflammation in the brain. Assessment of brain viral load showed mice virus detection five days post-infection in wild-type and CCR5−/− mice, while MIP-1 α−/− mice had lower viral loads seven days post-infection. Knockout mice required a higher lethal dose than wild-type mice as well. The CCR5/MIP-1 α axis may contribute to migration of infected cells to the brain and consequently affect the pathogenesis during ROCV infection. PMID:24080631

Eastern Equine Encephalitis in Latin America

PubMed Central

Carrera, Jean-Paul; Forrester, Naomi; Wang, Eryu; Vittor, Amy Y.; Haddow, Andrew D.; López-Vergès, Sandra; Abadía, Ivan; Castaño, Elizabeth; Sosa, Nestor; Báez, Carmen; Estripeaut, Dora; Díaz, Yamilka; Beltrán, Davis; Cisneros, Julio; Cedeño, Hector G.; da Rosa, Amelia P. Travassos; Hernandez, Humberto; Martínez-Torres, Alex O.; Tesh, Robert B.; Weaver, Scott C.

2013-01-01

BACKGROUND The eastern equine encephalitis (EEE) and Venezuelan equine encephalitis (VEE) viruses are pathogens that infect humans and horses in the Americas. Outbreaks of neurologic disease in humans and horses were reported in Panama from May through early August 2010. METHODS We performed antibody assays and tests to detect viral RNA and isolate the viruses in serum samples from hospitalized patients. Additional cases were identified with enhanced surveillance. RESULTS A total of 19 patients were hospitalized for encephalitis. Among them, 7 had confirmed EEE, 3 had VEE, and 1 was infected with both viruses; 3 patients died, 1 of whom had confirmed VEE. The clinical findings for patients with EEE included brain lesions, seizures that evolved to status epilepticus, and neurologic sequelae. An additional 99 suspected or probable cases of alphavirus infection were detected during active surveillance. In total, 13 cases were confirmed as EEE, along with 11 cases of VEE and 1 case of dual infection. A total of 50 cases in horses were confirmed as EEE and 8 as VEE; mixed etiologic factors were associated with 11 cases in horses. Phylogenetic analyses of isolates from 2 cases of equine infection with the EEE virus and 1 case of human infection with the VEE virus indicated that the viruses were of enzootic lineages previously identified in Panama rather than new introductions. CONCLUSIONS Cases of EEE in humans in Latin America may be the result of ecologic changes that increased human contact with enzootic transmission cycles, genetic changes in EEE viral strains that resulted in increased human virulence, or an altered host range. (Funded by the National Institutes of Health and the Secretaría Nacional de Ciencia, Tecnología e Innovación, Panama.) PMID:23964935

Distinguishing West Nile virus infection using a recombinant envelope protein with mutations in the conserved fusion-loop.

PubMed

Chabierski, Stefan; Barzon, Luisa; Papa, Anna; Niedrig, Matthias; Bramson, Jonathan L; Richner, Justin M; Palù, Giorgio; Diamond, Michael S; Ulbert, Sebastian

2014-05-09

West Nile Virus (WNV) is an emerging mosquito-transmitted flavivirus that continues to spread and cause disease throughout several parts of the world, including Europe and the Americas. Specific diagnosis of WNV infections using current serological testing is complicated by the high degree of cross-reactivity between antibodies against other clinically relevant flaviviruses, including dengue, tick-borne encephalitis (TBEV), Japanese encephalitis (JEV), and yellow fever (YFV) viruses. Cross-reactivity is particularly problematic in areas where different flaviviruses co-circulate or in populations that have been immunized with vaccines against TBEV, JEV, or YFV. The majority of cross-reactive antibodies against the immunodominant flavivirus envelope (E) protein target a conserved epitope in the fusion loop at the distal end of domain II. We tested a loss-of-function bacterially expressed recombinant WNV E protein containing mutations in the fusion loop and an adjacent loop domain as a possible diagnostic reagent. By comparing the binding of sera from humans infected with WNV or other flaviviruses to the wild type and the mutant E proteins, we analyzed the potential of this technology to specifically detect WNV antibodies. Using this system, we could reliably determine WNV infections. Antibodies from WNV-infected individuals bound equally well to the wild type and the mutant protein. In contrast, sera from persons infected with other flaviviruses showed significantly decreased binding to the mutant protein. By calculating the mean differences between antibody signals detected using the wild type and the mutant proteins, a value could be assigned for each of the flaviviruses, which distinguished their pattern of reactivity. Recombinant mutant E proteins can be used to discriminate infections with WNV from those with other flaviviruses. The data have important implications for the development of improved, specific serological assays for the detection of WNV antibodies in regions where other flaviviruses co-circulate or in populations that are immunized with other flavivirus vaccines.

Eastern Equine Encephalitis Virus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Borucki, M.

2010-08-05

Eastern equine encephalitis virus (EEEV) is a mosquito-borne virus capable of causing large outbreaks of encephalitis in humans and horses. In North America, EEEV infection has a very high mortality rate in humans, and survivors often suffer severe neurological sequelae. Interestingly, EEEV infections from South American isolates are generally subclinical. Although EEEV is divided into two antigenic varieties and four lineages, only eleven isolates have been sequenced and eight of these are from the North American variety (Lineage I). Most sequenced strains were collected from mosquitoes and only one human isolate has been sequenced. EEEV isolates exist from a varietymore » of hosts, vectors, years, and geographical locations and efforts should focus on sequencing strains that represent this diversity.« less

Surveillance for Western Equine Encephalitis, St. Louis Encephalitis, and West Nile Viruses Using Reverse Transcription Loop-Mediated Isothermal Amplification

PubMed Central

Wheeler, Sarah S.; Ball, Cameron S.; Langevin, Stanley A.; Fang, Ying; Coffey, Lark L.; Meagher, Robert J.

2016-01-01

Collection of mosquitoes and testing for vector-borne viruses is a key surveillance activity that directly influences the vector control efforts of public health agencies, including determining when and where to apply insecticides. Vector control districts in California routinely monitor for three human pathogenic viruses including West Nile virus (WNV), Western equine encephalitis virus (WEEV), and St. Louis encephalitis virus (SLEV). Reverse transcription quantitative polymerase chain reaction (RT-qPCR) offers highly sensitive and specific detection of these three viruses in a single multiplex reaction, but this technique requires costly, specialized equipment that is generally only available in centralized public health laboratories. We report the use of reverse transcription loop-mediated isothermal amplification (RT-LAMP) to detect WNV, WEEV, and SLEV RNA extracted from pooled mosquito samples collected in California, including novel primer sets for specific detection of WEEV and SLEV, targeting the nonstructural protein 4 (nsP4) gene of WEEV and the 3’ untranslated region (3’-UTR) of SLEV. Our WEEV and SLEV RT-LAMP primers allowed detection of <0.1 PFU/reaction of their respective targets in <30 minutes, and exhibited high specificity without cross reactivity when tested against a panel of alphaviruses and flaviviruses. Furthermore, the SLEV primers do not cross-react with WNV, despite both viruses being closely related members of the Japanese encephalitis virus complex. The SLEV and WEEV primers can also be combined in a single RT-LAMP reaction, with discrimination between amplicons by melt curve analysis. Although RT-qPCR is approximately one order of magnitude more sensitive than RT-LAMP for all three targets, the RT-LAMP technique is less instrumentally intensive than RT-qPCR and provides a more cost-effective method of vector-borne virus surveillance. PMID:26807734

Autoimmune encephalitis and its relation to infection.

PubMed

Venkatesan, Arun; Benavides, David R

2015-03-01

Encephalitis, an inflammatory condition of the brain that results in substantial morbidity and mortality, has numerous causes. Over the past decade, it has become increasingly recognized that autoimmune conditions contribute significantly to the spectrum of encephalitis causes. Clinical suspicion and early diagnosis of autoimmune etiologies are of particular importance due to the need for early institution of immune suppressive therapies to improve outcome. Emerging clinical observations suggest that the most commonly recognized cause of antibody-mediated autoimmune encephalitis, anti-N-methyl-D-aspartate (NMDA) receptor encephalitis, may in some cases be triggered by herpes virus infection. Other conditions such as Rasmussen's encephalitis (RE) and febrile infection-related epilepsy syndrome (FIRES) have also been posited to be autoimmune conditions triggered by infectious agents. This review focuses on emerging concepts in central nervous system autoimmunity and addresses clinical and mechanistic findings linking autoimmune encephalitis and infections. Particular consideration will be given to anti-NMDA receptor encephalitis and its relation to herpes simplex encephalitis.

Pathogenesis of Dengue Vaccine Viruses in Mosquitoes.

DTIC Science & Technology

1984-01-01

type 2 (Price, 1973), and attenuated Japanese encephalitis vaccine virus (Chen and Beaty, 1982). Sabin (1948) showed that attenuated dengue virus...M194 992 PATHOGENESIS OF DENGUJE VACCINE VIRUSES IN NOSSUITOES vi1 (u) COLORADO STATE UNIV FORT COLLINS DEPT OF MICROBIOLOGY AND ENVIRONMENTAL...IW AV wWW W N A A~~ Nq .. mcFILE COPY 0)0 AD PATHOGENESIS OF DENGUE VACCINE VIRUSES IN MOSQUITOES Annual Report Barry J. Beaty, Ph.D. D T IC ELECTE

The Complement System in Flavivirus Infections

PubMed Central

Conde, Jonas N.; Silva, Emiliana M.; Barbosa, Angela S.; Mohana-Borges, Ronaldo

2017-01-01

The incidence of flavivirus infections has increased dramatically in recent decades in tropical and sub-tropical climates worldwide, affecting hundreds of millions of people each year. The Flaviviridae family includes dengue, West Nile, Zika, Japanese encephalitis, and yellow fever viruses that are typically transmitted by mosquitoes or ticks, and cause a wide range of symptoms, such as fever, shock, meningitis, paralysis, birth defects, and death. The flavivirus genome is composed of a single positive-sense RNA molecule encoding a single viral polyprotein. This polyprotein is further processed by viral and host proteases into three structural proteins (C, prM/M, E) and seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, NS5) that are involved in viral replication and pathogenicity. The complement system has been described to play an important role in flavivirus infection either by protecting the host and/or by influencing disease pathogenesis. In this mini-review, we will explore the role of complement system inhibition and/or activation against infection by the Flavivirus genus, with an emphasis on dengue and West Nile viruses. PMID:28261172

Can Herpes Simplex Virus Encephalitis Cause Aphasia?

ERIC Educational Resources Information Center

Naude, H.; Pretorius, E.

2003-01-01

Aphasia implies the loss or impairment of language caused by brain damage. The key to understanding the nature of aphasic symptoms is the neuro-anatomical site of brain damage, and not the causative agent. However, because "Herpes simplex" virus (HSV) encephalitis infection usually affects the frontal and temporal lobes, subcortical…

Fatal human eosinophilic meningo-encephalitis caused by CNS co-infection with Halicephalobus gingivalis and West Nile virus.

PubMed

Anwar, M A; Gokozan, H N; Ball, M K; Otero, J; McGwire, B S

2015-10-01

The saprophytic nematode Halicephalobus is a rare cause of fatal human meningo-encephalitis, and West Nile virus is neurotropic flavivirus implicated in a variety of clinical neurologic syndromes. Here we report a case of rapidly progressive CNS encephalopathy and death. Serologic, immuno-histochemical, histopathologic and nucleic acid studies demonstrate the presence of active Halicephalobus and West Nile virus in the CNS tissue. This is the first reported case of co-infection with these neurotropic pathogens. Copyright © 2015. Published by Elsevier Ireland Ltd.

Nipah Virus Infection Outbreak with Nosocomial and Corpse-to-Human Transmission, Bangladesh

PubMed Central

Hossain, M. Jahangir; Gurley, Emily S.; Ameen, Kazi M.H.; Parveen, Shahana; Islam, M. Saiful; Faruque, Labib I.; Podder, Goutam; Banu, Sultana S.; Lo, Michael K.; Rollin, Pierre E.; Rota, Paul A.; Daszak, Peter; Rahman, Mahmudur; Luby, Stephen P.

2013-01-01

Active Nipah virus encephalitis surveillance identified an encephalitis cluster and sporadic cases in Faridpur, Bangladesh, in January 2010. We identified 16 case-patients; 14 of these patients died. For 1 case-patient, the only known exposure was hugging a deceased patient with a probable case, while another case-patient’s exposure involved preparing the same corpse for burial by removing oral secretions and anogenital excreta with a cloth and bare hands. Among 7 persons with confirmed sporadic cases, 6 died, including a physician who had physically examined encephalitis patients without gloves or a mask. Nipah virus–infected patients were more likely than community-based controls to report drinking raw date palm sap and to have had physical contact with an encephalitis patient (29% vs. 4%, matched odds ratio undefined). Efforts to prevent transmission should focus on reducing caregivers’ exposure to infected patients’ bodily secretions during care and traditional burial practices. PMID:23347678

Human West Nile Virus Disease Outbreak in Pakistan, 2015–2016

PubMed Central

Khan, Erum; Barr, Kelli L.; Farooqi, Joveria Qais; Prakoso, Dhani; Abbas, Alizae; Khan, Zain Y.; Ashi, Shanze; Imtiaz, Kehkashan; Aziz, Z.; Malik, Faisal; Lednicky, John A.; Long, Maureen T.

2018-01-01

Like most of the world, Pakistan has seen an increase in mosquito-transmitted diseases in recent years. The magnitude and distribution of these diseases are poorly understood as Pakistan does not have a nation-wide system for reporting disease. A cross-sectional study to determine which flaviviruses were causing of arboviral disease in Pakistan was instituted. West Nile virus (WNV) is a cause of seasonal fever with neurotropic findings in countries that share borders with Pakistan. Here, we describe the active and persistent circulation of WNV in humans in the southern region of Pakistan. This is the first report of WNV causing neurological disease in human patients in this country. Of 997 enrolled patients presenting with clinical features suggestive of arboviral disease, 105 were positive for WNV IgM antibodies, and 71 of these patients possessed WNV-specific neutralizing antibodies. Cross-reactivity of WNV IgM antibodies with Japanese encephalitis virus (JEV) occurred in 75 of these 105 patients. WNV co-infections with Dengue viruses were not a contributing factor for the severity of disease. Nor did prior exposure to dengue virus contribute to incidence of neurological involvement in WNV-infected patients. Patients with WNV infections were more likely to present with altered mental status, seizures, and reduced Glasgow Coma scores when compared with JEV-infected patients. Human WNV cases and vector numbers exhibited a temporal correlation with climate. PMID:29535994

Human West Nile Virus Disease Outbreak in Pakistan, 2015-2016.

PubMed

Khan, Erum; Barr, Kelli L; Farooqi, Joveria Qais; Prakoso, Dhani; Abbas, Alizae; Khan, Zain Y; Ashi, Shanze; Imtiaz, Kehkashan; Aziz, Z; Malik, Faisal; Lednicky, John A; Long, Maureen T

2018-01-01

Like most of the world, Pakistan has seen an increase in mosquito-transmitted diseases in recent years. The magnitude and distribution of these diseases are poorly understood as Pakistan does not have a nation-wide system for reporting disease. A cross-sectional study to determine which flaviviruses were causing of arboviral disease in Pakistan was instituted. West Nile virus (WNV) is a cause of seasonal fever with neurotropic findings in countries that share borders with Pakistan. Here, we describe the active and persistent circulation of WNV in humans in the southern region of Pakistan. This is the first report of WNV causing neurological disease in human patients in this country. Of 997 enrolled patients presenting with clinical features suggestive of arboviral disease, 105 were positive for WNV IgM antibodies, and 71 of these patients possessed WNV-specific neutralizing antibodies. Cross-reactivity of WNV IgM antibodies with Japanese encephalitis virus (JEV) occurred in 75 of these 105 patients. WNV co-infections with Dengue viruses were not a contributing factor for the severity of disease. Nor did prior exposure to dengue virus contribute to incidence of neurological involvement in WNV-infected patients. Patients with WNV infections were more likely to present with altered mental status, seizures, and reduced Glasgow Coma scores when compared with JEV-infected patients. Human WNV cases and vector numbers exhibited a temporal correlation with climate.

Postepizootic Persistence of Venezuelan Equine Encephalitis Virus, Venezuela

PubMed Central

Navarro, Juan-Carlos; Medina, Gladys; Vasquez, Clovis; Coffey, Lark L.; Wang, Eryu; Suárez, Alexander; Biord, Hernán; Salas, Marlene

2005-01-01

Five years after the apparent end of the major 1995 Venezuelan equine encephalitis (VEE) epizootic/epidemic, focal outbreaks of equine encephalitis occurred in Carabobo and Barinas States of western Venezuela. Virus isolates from horses in each location were nearly identical in sequence to 1995 isolates, which suggests natural persistence of subtype IC VEE virus (VEEV) strains in a genetically stable mode. Serologic evidence indicated that additional outbreaks occurred in Barinas State in 2003. Field studies identified known Culex (Melanoconion) spp. vectors and reservoir hosts of enzootic VEEV but a dearth of typical epidemic vectors. Cattle serosurveys indicated the recent circulation of enzootic VEEV strains, and possibly of epizootic strains. Persistence of VEEV subtype IC strains and infection of horses at the end of the rainy season suggest the possibility of an alternative, cryptic transmission cycle involving survival through the dry season of infected vectors or persistently infected vertebrates. PMID:16485478

[Activating effect of cyclophosphane at late stages of persistence of the tick-borne encephalitis virus].

PubMed

Frolova, T V; Pogodina, V V; Larina, G I; Frolova, M P; Karmysheva, V Ia

1982-01-01

Conditions of activation of persistent infection caused by subcutaneous inoculation of Syrian hamsters with the B-383 and Vasilchenko strains of tick-borne encephalitis virus (TBE) were studied. After 2 administrations of cyclophosphane (CP) on day 170 of infection clinically manifest disease developed in some animals with increasingly severe pathomorphological lesions in the CNS. Several variants of activated TBE virus were isolated from brains and spleens of CP-treated hamsters. The activation of persistent infection was observed in the presence of marked decreased of humoral immunity level, weight of the thymus, and values of spontaneous rosette-formation.

A Multiplex PCR/LDR Assay for the Simultaneous Identification of Category A Infectious Pathogens: Agents of Viral Hemorrhagic Fever and Variola Virus

PubMed Central

Das, Sanchita; Rundell, Mark S.; Mirza, Aashiq H.; Pingle, Maneesh R.; Shigyo, Kristi; Garrison, Aura R.; Paragas, Jason; Smith, Scott K.; Olson, Victoria A.; Larone, Davise H.; Spitzer, Eric D.; Barany, Francis; Golightly, Linnie M.

2015-01-01

CDC designated category A infectious agents pose a major risk to national security and require special action for public health preparedness. They include viruses that cause viral hemorrhagic fever (VHF) syndrome as well as variola virus, the agent of smallpox. VHF is characterized by hemorrhage and fever with multi-organ failure leading to high morbidity and mortality. Smallpox, a prior scourge, has been eradicated for decades, making it a particularly serious threat if released nefariously in the essentially non-immune world population. Early detection of the causative agents, and the ability to distinguish them from other pathogens, is essential to contain outbreaks, implement proper control measures, and prevent morbidity and mortality. We have developed a multiplex detection assay that uses several species-specific PCR primers to generate amplicons from multiple pathogens; these are then targeted in a ligase detection reaction (LDR). The resultant fluorescently-labeled ligation products are detected on a universal array enabling simultaneous identification of the pathogens. The assay was evaluated on 32 different isolates associated with VHF (ebolavirus, marburgvirus, Crimean Congo hemorrhagic fever virus, Lassa fever virus, Rift Valley fever virus, Dengue virus, and Yellow fever virus) as well as variola virus and vaccinia virus (the agent of smallpox and its vaccine strain, respectively). The assay was able to detect all viruses tested, including 8 sequences representative of different variola virus strains from the CDC repository. It does not cross react with other emerging zoonoses such as monkeypox virus or cowpox virus, or six flaviviruses tested (St. Louis encephalitis virus, Murray Valley encephalitis virus, Powassan virus, Tick-borne encephalitis virus, West Nile virus and Japanese encephalitis virus). PMID:26381398

A Multiplex PCR/LDR Assay for the Simultaneous Identification of Category A Infectious Pathogens: Agents of Viral Hemorrhagic Fever and Variola Virus.

PubMed

Das, Sanchita; Rundell, Mark S; Mirza, Aashiq H; Pingle, Maneesh R; Shigyo, Kristi; Garrison, Aura R; Paragas, Jason; Smith, Scott K; Olson, Victoria A; Larone, Davise H; Spitzer, Eric D; Barany, Francis; Golightly, Linnie M

2015-01-01

CDC designated category A infectious agents pose a major risk to national security and require special action for public health preparedness. They include viruses that cause viral hemorrhagic fever (VHF) syndrome as well as variola virus, the agent of smallpox. VHF is characterized by hemorrhage and fever with multi-organ failure leading to high morbidity and mortality. Smallpox, a prior scourge, has been eradicated for decades, making it a particularly serious threat if released nefariously in the essentially non-immune world population. Early detection of the causative agents, and the ability to distinguish them from other pathogens, is essential to contain outbreaks, implement proper control measures, and prevent morbidity and mortality. We have developed a multiplex detection assay that uses several species-specific PCR primers to generate amplicons from multiple pathogens; these are then targeted in a ligase detection reaction (LDR). The resultant fluorescently-labeled ligation products are detected on a universal array enabling simultaneous identification of the pathogens. The assay was evaluated on 32 different isolates associated with VHF (ebolavirus, marburgvirus, Crimean Congo hemorrhagic fever virus, Lassa fever virus, Rift Valley fever virus, Dengue virus, and Yellow fever virus) as well as variola virus and vaccinia virus (the agent of smallpox and its vaccine strain, respectively). The assay was able to detect all viruses tested, including 8 sequences representative of different variola virus strains from the CDC repository. It does not cross react with other emerging zoonoses such as monkeypox virus or cowpox virus, or six flaviviruses tested (St. Louis encephalitis virus, Murray Valley encephalitis virus, Powassan virus, Tick-borne encephalitis virus, West Nile virus and Japanese encephalitis virus).

Duck egg drop syndrome virus: an emerging Tembusu-related flavivirus in China.

PubMed

Liu, PeiPei; Lu, Hao; Li, Shuang; Wu, Ying; Gao, George Fu; Su, JingLiang

2013-08-01

Duck egg drop syndrome virus (DEDSV) is a newly emerging pathogenic flavivirus isolated from ducks in China. DEDSV infection mainly results in severe egg drop syndrome in domestic poultry, which leads to huge economic losses. Thus, the discovery of ways and means to combat DEDSV is urgent. Since 2010, a remarkable amount of progress concerning DEDSV research has been achieved. Here, we review current knowledge on the epidemiology, symptomatology, and pathology of DEDSV. A detailed dissection of the viral genome and polyprotein sequences, comparative analysis of viral antigenicity and the corresponding potential immunity against the virus are also summarized. Current findings indicate that DEDSV should be a distinct species from Tembusu virus. Moreover, the adaption of DEDSV in wildlife and its high homology to pathogenic flaviviruses (e.g., West Nile virus, Japanese encephalitis virus, and dengue virus), illustrate its reemergence and potential to become a zoonotic pathogen that should not be overlooked. Detailed insight into the antigenicity and corresponding immunity against the virus is of clear significance for the development of vaccines and antiviral drugs specific for DEDSV.

Characterization of codon usage pattern and influencing factors in Japanese encephalitis virus.

PubMed

Singh, Niraj K; Tyagi, Anuj; Kaur, Rajinder; Verma, Ramneek; Gupta, Praveen K

2016-08-02

Recently, several outbreaks of Japanese encephalitis (JE), caused by Japanese encephalitis virus (JEV), have been reported and it has become cause of concern across the world. In this study, detailed analysis of JEV codon usage pattern was performed. The relative synonymous codon usage (RSCU) values along with mean effective number of codons (ENC) value of 55.30 indicated the presence of low codon usages bias in JEV. The effect of mutational pressure on codon usage bias was confirmed by significant correlations of A3s, U3s, G3s, C3s, GC3s, ENC values, with overall nucleotide contents (A%, U%, G%, C%, and GC%). The correlation analysis of A3s, U3s, G3s, C3s, GC3s, with axis values of correspondence analysis (CoA) further confirmed the role of mutational pressure. However, the correlation analysis of Gravy values and Aroma values with A3s, U3s, G3s, C3s, and GC3s, indicated the presence of natural selection on codon usage bias in addition to mutational pressure. The natural selection was further confirmed by codon adaptation index (CAI) analysis. Additionally, relative dinucleotide frequencies, geographical distribution, and evolutionary processes also influenced the codon usage pattern to some extent. Copyright © 2016 Elsevier B.V. All rights reserved.

Viral Etiology of Encephalitis in Children in Southern Vietnam: Results of a One-Year Prospective Descriptive Study

PubMed Central

Tan, Le Van; Qui, Phan Tu; Ha, Do Quang; Hue, Nguyen Bach; Bao, Lam Quoi; Cam, Bach Van; Khanh, Truong Huu; Hien, Tran Tinh; Vinh Chau, Nguyen Van; Tram, Tran Tan; Hien, Vo Minh; Nga, Tran Vu Thieu; Schultsz, Constance; Farrar, Jeremy; van Doorn, H. Rogier; de Jong, Menno D.

2010-01-01

Background Acute encephalitis is an important and severe disease in children in Vietnam. However, little is known about the etiology while such knowledge is essential for optimal prevention and treatment. To identify viral causes of encephalitis, in 2004 we conducted a one-year descriptive study at Children's Hospital Number One, a referral hospital for children in southern Vietnam including Ho Chi Minh City. Methodology/Principal Findings Children less than 16 years of age presenting with acute encephalitis of presumed viral etiology were enrolled. Diagnostic efforts included viral culture, serology and real time (RT)-PCRs. A confirmed or probable viral causative agent was established in 41% of 194 enrolled patients. The most commonly diagnosed causative agent was Japanese encephalitis virus (n = 50, 26%), followed by enteroviruses (n = 18, 9.3%), dengue virus (n = 9, 4.6%), herpes simplex virus (n = 1), cytomegalovirus (n = 1) and influenza A virus (n = 1). Fifty-seven (29%) children died acutely. Fatal outcome was independently associated with patient age and Glasgow Coma Scale (GCS) on admission. Conclusions/Significance Acute encephalitis in children in southern Vietnam is associated with high mortality. Although the etiology remains unknown in a majority of the patients, the result from the present study may be useful for future design of treatment and prevention strategies of the disease. The recognition of GCS and age as predictive factors may be helpful for clinicians in managing the patient. PMID:21049060

Aetiology of acute encephalitis syndrome in Uttar Pradesh, India from 2014 to 2016.

PubMed

Jain, Parul; Prakash, Shantanu; Khan, Danish N; Garg, Ravindra Kumar; Kumar, Rashmi; Bhagat, Amit; Ramakrishna, V; Jain, Amita

2017-01-01

It is imperative to know the aetiology of acute encephalitis syndrome (AES) for patient management and policy making. The present study was carried out to determine the prevalence of common aetiological agents of AES in Uttar Pradesh (UP) state of India. Serum and/or CSF samples were collected from AES patients admitted at Gandhi Memorial and Associated Hospital, King George's Medical University, Lucknow, a tertiary care centre, UP during 2014-16. Cerebrospinal fluid (CSF) and serum samples from cases were tested for IgM antibodies against Japanese encephalitis virus (anti-JEV), and dengue virus (anti-DENV) by ELISA; and for enterovirus, herpes simplex virus (HSV) and varicella zoster virus (VZV) by real-time PCR. Serum samples of cases having sufficient CSF volume, were also tested for anti-scrub typhus IgM antibodies and for Neisseria meningitides, Streptococcus pneumoniae and Haemophilus influenzae. JEV and DENV (8% each) were the most common identified aetiology from the 4092 enrolled patients. Enterovirus, HSV and VZV, each were detected in <1% AES cases. Co-positivity occurred in 48 cases. Scrub typhus (31.8%) was the most common aetiology detected. Haemophilus influenzae and S. pneumoniae were detected in 0.97 and 0.94% cases, respectively, however, N. meningitides was not detected in any of the cases. About 40% of the JEV/DENV positive AES cases were adults. The gap between the total number of AES cases and those with JEV/ DENV infection increased during monsoon and post-monsoon seasons. Scrub typhus, JEV and DENV are the main aetiological agents of AES in UP. DENV and JEV can no longer be considered paediatric diseases. The prevalence of non-JEV/DENV aetiology of AES increases in the monsoon and post-monsoon seasons.

Nominal dysphasia and euphoria caused by EBV encephalitis

PubMed Central

Carman, Kursat Bora; Yakut, Ayten; Ekici, Arzu; Isikay, Sedat

2013-01-01

Encephalitis is an uncommon neurological complication of Ebstein-Barr virus (EBV) infection and usually presents with confusion, decreased level of consciousness, fever, epileptic seizure, emotional instability and chorea. We present a patient with EBV encephalitis, characterised by nominal dysphasia, euphoria and personality changes. PMID:23307455

Absent anti-N-methyl-D-aspartate receptor NR1a antibodies in herpes simplex virus encephalitis and varicella zoster virus infections.

PubMed

Berger, Benjamin; Pytlik, Maximilian; Hottenrott, Tilman; Stich, Oliver

2017-02-01

A 2012 report and subsequent case series described anti-N-methyl-D-aspartate receptor (NMDAR) antibodies in patients during the acute phase and relapse of herpes simplex virus 1 (HSV1) encephalitis (HSV1E). However, the prevalence of this phenomenon is unknown and systematic studies on other viral infections of the nervous system are missing. We retrospectively analyzed serial cerebrospinal fluid (CSF) and serum samples of consecutive patients treated for neurological HSV1, HSV2 and varicella zoster virus (VZV) infections in our tertiary care university hospital between 2003 and 2013 for the presence of antibodies directed against the NR1a subunit of the NMDAR using indirect immunofluorescence. In total, 88 patients with the following infections were identified through an electronic database search: HSV1 (24 with encephalitis), HSV2 (6 with meningitis, 3 with encephalitis and 1 with myelitis), or VZV (3 with meningitis, 33 with encephalitis, 17 with radiculitis and 1 with myelitis). Two patients with HSV1E and HSV2E, respectively, experienced a clinical relapse. Clinical follow-up was for up to 85 months, and repetitive serum and CSF analyses for up to 43 months. However, at no time did any of the 88 patients exhibit anti-NMDAR NR1a antibodies. In this study, we did not detect anti-NMDAR NR1a antibodies in serial CSF and serum samples of HSV1E patients or patients with other viral infections (HSV2 and VZV). However, the presence of antibodies directed against other epitopes of the NMDAR and other neuronal cell surface antigens cannot be excluded, necessitating further studies.

Chikungunya infection presenting as mild encephalitis with a reversible lesion in the splenium: a case report.

PubMed

Nagpal, Kadam; Agarwal, Puneet; Kumar, Amit; Reddi, Rajashekhar

2017-06-01

Chikungunya fever is an Aedes mosquito-transmitted infection caused by chikungunya virus, an RNA virus in the family Togaviridae. The disease is characteristically manifested as fever, arthralgia, and/or rash. Various neurological manifestations like meningoencephalitis, myelitis, and myeloneuropathy have been mentioned in various reports. We present a rare case of chikungunya fever presenting with mild encephalitis with a reversible lesion of the splenium (MERS), which showed complete clinical and radiological recovery.

Herpes Simplex Virus-1 Encephalitis in Adults: Pathophysiology, Diagnosis, and Management.

PubMed

Bradshaw, Michael J; Venkatesan, Arun

2016-07-01

Herpetic infections have plagued humanity for thousands of years, but only recently have advances in antiviral medications and supportive treatments equipped physicians to combat the most severe manifestations of disease. Prompt recognition and treatment can be life-saving in the care of patients with herpes simplex-1 virus encephalitis, the most commonly identified cause of sporadic encephalitis worldwide. Clinicians should be able to recognize the clinical signs and symptoms of the infection and familiarize themselves with a rational diagnostic approach and therapeutic modalities, as early recognition and treatment are key to improving outcomes. Clinicians should also be vigilant for the development of acute complications, including cerebral edema and status epilepticus, as well as chronic complications, including the development of autoimmune encephalitis associated with antibodies to the N-methyl-D-aspartate receptor and other neuronal cell surface and synaptic epitopes. Herein, we review the pathophysiology, differential diagnosis, and clinical and radiological features of herpes simplex virus-1 encephalitis in adults, including a discussion of the most common complications and their treatment. While great progress has been made in the treatment of this life-threatening infection, a majority of patients will not return to their previous neurologic baseline, indicating the need for further research efforts aimed at improving the long-term sequelae.

West Nile virus infection in killer whale, Texas, USA, 2007.

PubMed

St Leger, Judy; Wu, Guang; Anderson, Mark; Dalton, Les; Nilson, Erika; Wang, David

2011-08-01

In 2007, nonsuppurative encephalitis was identified in a killer whale at a Texas, USA, marine park. Panviral DNA microarray of brain tissue suggested West Nile virus (WNV); WNV was confirmed by reverse transcription PCR and sequencing. Immunohistochemistry demonstrated WNV antigen within neurons. WNV should be considered in cases of encephalitis in cetaceans.

Japanese encephalitis surveillance and immunization--Asia and the Western Pacific, 2012.

PubMed

2013-08-23

Japanese encephalitis (JE) virus is a leading cause of encephalitis in Asia, causing an estimated 67,900 JE cases annually. To control JE, the World Health Organization (WHO) recommends that JE vaccine be incorporated into immunization programs in all areas where JE is a public health problem. For many decades, progress mainly occurred in a small number of high-income Asian countries. Recently, prospects for control have improved with better disease burden awareness as a result of increased JE surveillance and wider availability of safe, effective vaccines. This report summarizes the status of JE surveillance and immunization programs in 2012 in Asia and the Western Pacific. Data were obtained from the WHO/United Nations Children's Fund (UNICEF) Joint Reporting Form (JRF), published literature, meeting reports, and websites. In 2012, 18 (75%) of the 24 countries with areas of JE virus transmission risk conducted at least some JE surveillance, and 11 (46%) had a JE immunization program. Further progress toward JE control requires increased awareness of disease burden at the national and regional levels, availability of WHO-prequalified pediatric JE vaccines, and international support for surveillance and vaccine introduction in countries with limited resources.

Crystal Structure of the Japanese Encephalitis Virus Envelope Protein

DOE Office of Scientific and Technical Information (OSTI.GOV)

Luca, Vincent C.; AbiMansour, Jad; Nelson, Christopher A.

2012-03-13

Japanese encephalitis virus (JEV) is the leading global cause of viral encephalitis. The JEV envelope protein (E) facilitates cellular attachment and membrane fusion and is the primary target of neutralizing antibodies. We have determined the 2.1-{angstrom} resolution crystal structure of the JEV E ectodomain refolded from bacterial inclusion bodies. The E protein possesses the three domains characteristic of flavivirus envelopes and epitope mapping of neutralizing antibodies onto the structure reveals determinants that correspond to the domain I lateral ridge, fusion loop, domain III lateral ridge, and domain I-II hinge. While monomeric in solution, JEV E assembles as an antiparallel dimermore » in the crystal lattice organized in a highly similar fashion as seen in cryo-electron microscopy models of mature flavivirus virions. The dimer interface, however, is remarkably small and lacks many of the domain II contacts observed in other flavivirus E homodimers. In addition, uniquely conserved histidines within the JEV serocomplex suggest that pH-mediated structural transitions may be aided by lateral interactions outside the dimer interface in the icosahedral virion. Our results suggest that variation in dimer structure and stability may significantly influence the assembly, receptor interaction, and uncoating of virions.« less

Crystal structure of the Japanese encephalitis virus envelope protein.

PubMed

Luca, Vincent C; AbiMansour, Jad; Nelson, Christopher A; Fremont, Daved H

2012-02-01

Japanese encephalitis virus (JEV) is the leading global cause of viral encephalitis. The JEV envelope protein (E) facilitates cellular attachment and membrane fusion and is the primary target of neutralizing antibodies. We have determined the 2.1-Å resolution crystal structure of the JEV E ectodomain refolded from bacterial inclusion bodies. The E protein possesses the three domains characteristic of flavivirus envelopes and epitope mapping of neutralizing antibodies onto the structure reveals determinants that correspond to the domain I lateral ridge, fusion loop, domain III lateral ridge, and domain I-II hinge. While monomeric in solution, JEV E assembles as an antiparallel dimer in the crystal lattice organized in a highly similar fashion as seen in cryo-electron microscopy models of mature flavivirus virions. The dimer interface, however, is remarkably small and lacks many of the domain II contacts observed in other flavivirus E homodimers. In addition, uniquely conserved histidines within the JEV serocomplex suggest that pH-mediated structural transitions may be aided by lateral interactions outside the dimer interface in the icosahedral virion. Our results suggest that variation in dimer structure and stability may significantly influence the assembly, receptor interaction, and uncoating of virions.

Emerging viral diseases of Southeast Asia and the Western Pacific.

PubMed Central

Mackenzie, J. S.; Chua, K. B.; Daniels, P. W.; Eaton, B. T.; Field, H. E.; Hall, R. A.; Halpin, K.; Johansen, C. A.; Kirkland, P. D.; Lam, S. K.; McMinn, P.; Nisbet, D. J.; Paru, R.; Pyke, A. T.; Ritchie, S. A.; Siba, P.; Smith, D. W.; Smith, G. A.; van den Hurk, A. F.; Wang, L. F.; Williams, D. T.

2001-01-01

Over the past 6 years, a number of zoonotic and vectorborne viral diseases have emerged in Southeast Asia and the Western Pacific. Vectorborne disease agents discussed in this article include Japanese encephalitis, Barmah Forest, Ross River, and Chikungunya viruses. However, most emerging viruses have been zoonotic, with fruit bats, including flying fox species as the probable wildlife hosts, and these will be discussed as well. The first of these disease agents to emerge was Hendra virus, formerly called equine morbillivirus. This was followed by outbreaks caused by a rabies-related virus, Australian bat lyssavirus, and a virus associated with porcine stillbirths and malformations, Menangle virus. Nipah virus caused an outbreak of fatal pneumonia in pigs and encephalitis in humans in the Malay Peninsula. Most recently, Tioman virus has been isolated from flying foxes, but it has not yet been associated with animal or human disease. Of nonzoonotic viruses, the most important regionally have been enterovirus 71 and HIV. PMID:11485641

Herpes simplex virus-1 evasion of CD8+ T cell accumulation contributes to viral encephalitis.

PubMed

Koyanagi, Naoto; Imai, Takahiko; Shindo, Keiko; Sato, Ayuko; Fujii, Wataru; Ichinohe, Takeshi; Takemura, Naoki; Kakuta, Shigeru; Uematsu, Satoshi; Kiyono, Hiroshi; Maruzuru, Yuhei; Arii, Jun; Kato, Akihisa; Kawaguchi, Yasushi

2017-10-02

Herpes simplex virus-1 (HSV-1) is the most common cause of sporadic viral encephalitis, which can be lethal or result in severe neurological defects even with antiviral therapy. While HSV-1 causes encephalitis in spite of HSV-1-specific humoral and cellular immunity, the mechanism by which HSV-1 evades the immune system in the central nervous system (CNS) remains unknown. Here we describe a strategy by which HSV-1 avoids immune targeting in the CNS. The HSV-1 UL13 kinase promotes evasion of HSV-1-specific CD8+ T cell accumulation in infection sites by downregulating expression of the CD8+ T cell attractant chemokine CXCL9 in the CNS of infected mice, leading to increased HSV-1 mortality due to encephalitis. Direct injection of CXCL9 into the CNS infection site enhanced HSV-1-specific CD8+ T cell accumulation, leading to marked improvements in the survival of infected mice. This previously uncharacterized strategy for HSV-1 evasion of CD8+ T cell accumulation in the CNS has important implications for understanding the pathogenesis and clinical treatment of HSV-1 encephalitis.

CSF herpes virus and autoantibody profiles in the evaluation of encephalitis

PubMed Central

Linnoila, Jenny J.; Binnicker, Matthew J.; Majed, Masoud; Klein, Christopher J.

2016-01-01

Objective: To report the frequency of coexisting herpes viruses (herpes simplex virus 1 [HSV-1] or HSV-2, varicella zoster virus, Epstein-Barr virus [EBV], cytomegalovirus, or human herpes virus 6 [HHV-6]) and autoantibodies in patients with encephalitis (herpes or autoimmune) in clinical laboratory service. Methods: Three groups were evaluated for herpes viruses and antibodies: group 1—patients whose CSF was positive for a herpes virus by real-time PCR over a period of 6 months; group 2—patients whose CSF was positive for an autoimmune encephalitis–associated antibody over 5 years (e.g., NMDA receptor [NMDA-R] antibody), and the same number of controls without autoimmune/infectious disease; and group 3—incidental autoimmune parainfectious encephalitis cases encountered over 1 year. Results: In group 1, antibodies were detected in 27 of 100 herpes PCR-positive CSF specimens (CSFs), either unclassified neural or nonneural in all but one patient with NMDA-R antibody detected after EBV infection. Antibodies were also detected in 3 of 7 CSFs submitted for repeat PCR testing (unclassified, 2; AMPA receptor, 1). In group 2, herpes viruses were detected in 1 of 77 controls (HHV-6) and 4 of 77 patients with autoimmune encephalitis (EBV, 2; HHV-6, 2); autoantibodies targeted NMDA-R in 3/4 and GABAB-R in 1/4. In group 3, NMDA-R antibody was detected in 7 patients post–HSV-1 encephalitis. Of the remaining 3 patients, 2 had unclassified neural antibodies detected, and one had GABAB-R autoimmunity. Concomitant neoplasms were discovered in 2 patients each from groups 2 and 3. Conclusions: Autoantibodies and herpes virus DNA frequently coexist in encephalitic CSF. Some patients develop parainfectious autoimmunity following viral CNS infection (usually HSV-1 encephalitis). The significance of detecting herpes nucleic acids in others remains unclear. PMID:27308306

Japanese encephalitis in a 114-month-old cow: pathological investigation of the affected cow and genetic characterization of Japanese encephalitis virus isolate

PubMed Central

2014-01-01

Background Japanese encephalitis virus (JEV) is classified into the genus Flavivirus in the family Flaviviridae. JEV can cause febrile illness and encephalitis mainly in humans and horses, and occasionally in cattle. Case presentation In late September 2010, a 114-month-old cow showed neurological symptoms similar to the symptoms observed in previous bovine cases of Japanese encephalitis (JE); therefore, we conducted virological and pathological tests on the cow. As a result, JEV was isolated from the cerebrum of the affected cow. We determined the complete genome sequence of the JEV isolate, which we named JEV/Bo/Aichi/1/2010, including the envelope (E) gene region and 3’ untranslated region (3’UTR). Our phylogenetic analyses of the E region and complete genome showed that the isolate belongs to JEV genotype 1 (G1). The isolate, JEV/Bo/Aichi/1/2010, was most closely related to several JEV G1 isolates in Toyama Prefecture, Japan in 2007–2009 by the phylogenetic analysis of the E region. In addition, the nucleotide alignment revealed that the deletion in the 3’UTR was the same between JEV/Bo/Aichi/1/2010 and several other JEV G1 isolates identified in Toyama Prefecture in 2008–2009. A hemagglutination inhibition (HI) test was conducted for the detection of anti-JEV antibodies in the affected cow, and the test detected 2-mercaptoethanol (2-ME)-sensitive HI antibodies against JEV in the serum of the affected cow. The histopathological investigation revealed nonsuppurative encephalomyelitis in the affected cow, and the immunohistochemical assay detected JEV antigen in the cerebrum. Conclusion We diagnosed the case as JE of a cow based on the findings of nonsuppurative encephalomyelitis observed in the central nervous system, JEV antigen detected in the cerebrum, JEV isolated from the cerebrum, and 2-ME-sensitive HI antibodies against JEV detected in the serum. This is the first reported case of JE in a cow over 24 months old. PMID:24618225

Evaluation of a Field-Portable DNA Microarray Platform and Nucleic Acid Amplification Strategies for the Detection of Arboviruses, Arthropods, and Bloodmeals

PubMed Central

Grubaugh, Nathan D.; Petz, Lawrence N.; Melanson, Vanessa R.; McMenamy, Scott S.; Turell, Michael J.; Long, Lewis S.; Pisarcik, Sarah E.; Kengluecha, Ampornpan; Jaichapor, Boonsong; O'Guinn, Monica L.; Lee, John S.

2013-01-01

Highly multiplexed assays, such as microarrays, can benefit arbovirus surveillance by allowing researchers to screen for hundreds of targets at once. We evaluated amplification strategies and the practicality of a portable DNA microarray platform to analyze virus-infected mosquitoes. The prototype microarray design used here targeted the non-structural protein 5, ribosomal RNA, and cytochrome b genes for the detection of flaviviruses, mosquitoes, and bloodmeals, respectively. We identified 13 of 14 flaviviruses from virus inoculated mosquitoes and cultured cells. Additionally, we differentiated between four mosquito genera and eight whole blood samples. The microarray platform was field evaluated in Thailand and successfully identified flaviviruses (Culex flavivirus, dengue-3, and Japanese encephalitis viruses), differentiated between mosquito genera (Aedes, Armigeres, Culex, and Mansonia), and detected mammalian bloodmeals (human and dog). We showed that the microarray platform and amplification strategies described here can be used to discern specific information on a wide variety of viruses and their vectors. PMID:23249687

[Emerging viral diseases in Europe].

PubMed

Löbermann, M; Gürtler, L G; Eichler-Löbermann, B; Reisinger, E C

2012-04-01

Emergence of viral agents in Europe is influenced by various factors. Climatic changes influencing possible vectors, insufficient vaccination, and travel of man and goods are among the most important reasons to explain these changes. Fever and arthralgia are the leading symptoms in infection with Dengue, Sindbis, or Chikungunya virus. In contrast, tick-born encephalitis (TBE), Toscana, or West Nile virus infections mainly lead to meningo-encephalitis. In Europe, hemorrhagic fever is caused by Crimean Congo and Hanta virus. Protective vaccines are available for emerging viral agents like TBE, influenza and measles. © Georg Thieme Verlag KG Stuttgart · New York.

Powassan virus encephalitis resembling herpes simplex encephalitis.

PubMed

Embil, J A; Camfield, P; Artsob, H; Chase, D P

1983-02-01

A boy from New York traveling in Nova Scotia had olfactory hallucinations and other signs of temporal lobe involvement, leading to a diagnosis of herpes simplex encephalitis. The patient was treated with vidarabine and made a complete recovery. However, hemagglutination inhibition, complement fixation, and neutralization tests identified Powassan virus (POW) as the pathogen. Shortly before his trip to Nova Scotia, the patient had traveled in an area where POW encephalitis had occurred in humans (the eastern part of the state of New York), and he also came in contact with a known reservoir of POW infection (a groundhog) at home.

[Activating effect of adrenaline, prednisolone and vincristine in the late periods of tick-borne encephalitis virus persistence].

PubMed

Frolova, T V; Pogodina, V V

1984-01-01

The activating effect of adrenalin (A), prednisolone (P), and vincristine (V) on persistent infection caused by subcutaneous inoculation of Syrian hamsters with the Vasilchenko and B-383 strains of tick-borne encephalitis virus (TBE) was studied. The drugs were administered once, twice, or three times 250-270 days after virus inoculation. Complement-fixing antigen was found in the organs of the infected animals given no A, P, or V; in the organ explants synthesis of hemagglutinin was observed but no infectious virus could be isolated. After treatment of the infected hamsters with A, P, or V organ explants yielded TBE virus strains which showed either high or low virulence for white mice. The activated TBE virus strains were obtained from explants of hamster brains and spleens but not liver. V produced the most marked activating effect, A the least.

Infectious Causes of Encephalitis and Meningoencephalitis in Thailand, 2003–2005

PubMed Central

Campbell, Angela P.; Supawat, Krongkaew; Liamsuwan, Sahas; Chotpitayasunondh, Tawee; Laptikulthum, Somsak; Viriyavejakul, Akravudh; Tantirittisak, Tasanee; Tunlayadechanont, Supoch; Visudtibhan, Anannit; Vasiknanonte, Punnee; Janjindamai, Supachai; Boonluksiri, Pairoj; Rajborirug, Kiatsak; Watanaveeradej, Veerachai; Khetsuriani, Nino; Dowell, Scott F.

2015-01-01

Acute encephalitis is a severe neurologic syndrome. Determining etiology from among ≈100 possible agents is difficult. To identify infectious etiologies of encephalitis in Thailand, we conducted surveillance in 7 hospitals during July 2003–August 2005 and selected patients with acute onset of brain dysfunction with fever or hypothermia and with abnormalities seen on neuroimages or electroencephalograms or with cerebrospinal fluid pleocytosis. Blood and cerebrospinal fluid were tested for >30 pathogens. Among 149 case-patients, median age was 12 (range 0–83) years, 84 (56%) were male, and 15 (10%) died. Etiology was confirmed or probable for 54 (36%) and possible or unknown for 95 (64%). Among confirmed or probable etiologies, the leading pathogens were Japanese encephalitis virus, enteroviruses, and Orientia tsutsugamushi. No samples were positive for chikungunya, Nipah, or West Nile viruses; Bartonella henselae; or malaria parasites. Although a broad range of infectious agents was identified, the etiology of most cases remains unknown. PMID:25627940

THE PATHOGENESIS OF HERPES VIRUS ENCEPHALITIS

PubMed Central

Johnson, Richard T.

1964-01-01

The pathogenesis of herpes simplex virus encephalitis and myelitis was studied in suckling mice using routine titration procedures and fluorescent antibody staining for the identification of infected cells. After intracerebral inoculation virus was shown to disperse rapidly in the cerebrospinal fluid (CSF), multiply in meninges and ependyma, and then invade the underlying parenchyma infecting both neurons and glia. Following extraneural inoculation virus gained access to the central nervous system (CNS) by both hematogenous and neural pathways. After intraperitoneal and intranasal inoculation virus was found to multiply in viscera and produce viremia; foci of CNS infection then developed around small cerebral vessels. After subcutaneous and intranasal inoculation neural spread of virus was demonstrated along corresponding peripheral and cranial nerves. This spread resulted from the centripetal infection of endoneural cells (Schwann cells and fibroblasts). Antigen was not found in axons even after infection of the corresponding ganglion cell perikaryon. Subsequent spread within the CNS was unrelated to neural tracts, and there was no evidence of axonal spread of virus in the host-virus system studied. These findings are discussed in relation to previous and current theories of the viral "blood-brain barrier" and neural pathways of infection. PMID:14164487

Zika virus: a new pandemic threat.

PubMed

Al-Qahtani, Ahmed Ali; Nazir, Nyla; Al-Anazi, Mashael R; Rubino, Salvatore; Al-Ahdal, Mohammed N

2016-03-31

Zika virus (ZIKV) is an emerging arbovirus of the Flaviviridae family and is related to dengue, Chikungunya, West Nile, yellow fever, and Japanese encephalitis viruses. ZIKV was first discovered in Uganda in 1947. Different species of mosquito from the Aedes genus, mainly A. aegypti and A. albopictus are the vectors responsible for ZIKV infection in humans. It is also reported that ZIKV is transmitted congenitally, sexually, and through blood donation. Until recently, ZIKV outbreaks were sporadic and self-limiting. The first large epidemic was reported from Yap Island in 2007 followed by an outbreak of Zika fever in French Polynesia in 2013. Brazil is the epicenter of the current ZIKV epidemic which is rapidly spreading across the Americas. ZIKV infection remained relatively less studied in view of its low case numbers, and low clinical impact relative to other arboviruses. However, all this is set to change with its rapid spread in the Western hemisphere and suspected complications particularly microcephaly in newborn babies with ZIKV infected mothers. ZIKV is expected to substantially add to both short-term and long-term economic burden of the effected countries. Due to the large number of people travelling across the borders and some reported cases of transmission of ZIKV via contaminated blood, screening and identification of asymptomatic infected individuals are important.

Cholesterol effectively blocks entry of flavivirus.

PubMed

Lee, Chyan-Jang; Lin, Hui-Ru; Liao, Ching-Len; Lin, Yi-Ling

2008-07-01

Japanese encephalitis virus (JEV) and dengue virus serotype 2 (DEN-2) are enveloped flaviviruses that enter cells through receptor-mediated endocytosis and low pH-triggered membrane fusion and then replicate in intracellular membrane structures. Lipid rafts, cholesterol-enriched lipid-ordered membrane domains, are platforms for a variety of cellular functions. In this study, we found that disruption of lipid raft formation by cholesterol depletion with methyl-beta-cyclodextrin or cholesterol chelation with filipin III reduces JEV and DEN-2 infection, mainly at the intracellular replication steps and, to a lesser extent, at viral entry. Using a membrane flotation assay, we found that several flaviviral nonstructural proteins are associated with detergent-resistant membrane structures, indicating that the replication complex of JEV and DEN-2 localizes to the membranes that possess the lipid raft property. Interestingly, we also found that addition of cholesterol readily blocks flaviviral infection, a result that contrasts with previous reports of other viruses, such as Sindbis virus, whose infectivity is enhanced by cholesterol. Cholesterol mainly affected the early step of the flavivirus life cycle, because the presence of cholesterol during viral adsorption greatly blocked JEV and DEN-2 infectivity. Flavirial entry, probably at fusion and RNA uncoating steps, was hindered by cholesterol. Our results thus suggest a stringent requirement for membrane components, especially with respect to the amount of cholesterol, in various steps of the flavivirus life cycle.

West Nile Virus Infection in Killer Whale, Texas, USA, 2007

PubMed Central

Wu, Guang; Anderson, Mark; Dalton, Les; Nilson, Erika; Wang, David

2011-01-01

In 2007, nonsuppurative encephalitis was identified in a killer whale at a Texas, USA, marine park. Panviral DNA microarray of brain tissue suggested West Nile virus (WNV); WNV was confirmed by reverse transcription PCR and sequencing. Immunohistochemistry demonstrated WNV antigen within neurons. WNV should be considered in cases of encephalitis in cetaceans. PMID:21801643

Which Dengue Vaccine Approach Is the Most Promising, and Should We Be Concerned about Enhanced Disease after Vaccination? The Path to a Dengue Vaccine: Learning from Human Natural Dengue Infection Studies and Vaccine Trials.

PubMed

de Silva, Aravinda M; Harris, Eva

2018-06-01

Dengue virus (DENV) is the most common arthropod-borne viral disease of humans. Although effective vaccines exist against other flaviviral diseases like yellow fever and Japanese encephalitis, dengue vaccine development is complicated by the presence of four virus serotypes and the possibility of partial immunity enhancing dengue disease severity. Several live attenuated dengue vaccines are being tested in human clinical trials. Initial results are mixed, with variable efficacy depending on DENV serotype and previous DENV exposure. Here, we highlight recent discoveries about the human antibody response to DENV and propose guidelines for advancing development of safe and effective dengue vaccines. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

A Neuron-Specific Antiviral Mechanism Prevents Lethal Flaviviral Infection of Mosquitoes

PubMed Central

Xiao, Xiaoping; Zhang, Rudian; Pang, Xiaojing; Liang, Guodong; Wang, Penghua; Cheng, Gong

2015-01-01

Mosquitoes are natural vectors for many etiologic agents of human viral diseases. Mosquito-borne flaviviruses can persistently infect the mosquito central nervous system without causing dramatic pathology or influencing the mosquito behavior and lifespan. The mechanism by which the mosquito nervous system resists flaviviral infection is still largely unknown. Here we report that an Aedes aegypti homologue of the neural factor Hikaru genki (AaHig) efficiently restricts flavivirus infection of the central nervous system. AaHig was predominantly expressed in the mosquito nervous system and localized to the plasma membrane of neural cells. Functional blockade of AaHig enhanced Dengue virus (DENV) and Japanese encephalitis virus (JEV), but not Sindbis virus (SINV), replication in mosquito heads and consequently caused neural apoptosis and a dramatic reduction in the mosquito lifespan. Consistently, delivery of recombinant AaHig to mosquitoes reduced viral infection. Furthermore, the membrane-localized AaHig directly interfaced with a highly conserved motif in the surface envelope proteins of DENV and JEV, and consequently interrupted endocytic viral entry into mosquito cells. Loss of either plasma membrane targeting or virion-binding ability rendered AaHig nonfunctional. Interestingly, Culex pipien pallens Hig also demonstrated a prominent anti-flavivirus activity, suggesting a functionally conserved function for Hig. Our results demonstrate that an evolutionarily conserved antiviral mechanism prevents lethal flaviviral infection of the central nervous system in mosquitoes, and thus may facilitate flaviviral transmission in nature. PMID:25915054

The spectrum of aseptic central nervous system infections in southern Germany - demographic, clinical and laboratory findings.

PubMed

Kaminski, M; Grummel, V; Hoffmann, D; Berthele, A; Hemmer, B

2017-08-01

Aseptic infections of the central nervous system (CNS) are frequently observed in Germany. However, no study has systematically addressed the spectrum of aseptic CNS infections in Germany. Data on 191 adult patients diagnosed from January 2007 to December 2014 with aseptic meningitis or encephalitis/meningoencephalitis at our hospital were collected by chart review and analyzed for demographic, clinical and laboratory findings. Patients were stratified according to the causative virus and findings were compared between groups. In our cohort, meningitis was caused in 36% by enterovirus (EV), 15% by herpes simplex virus (HSV), 12% by varicella zoster virus (VZV) and 5% by tick borne encephalitis (TBE). Encephalitis/meningoencephalitis was caused in 13% by HSV, 13% by VZV, and three out of 11 tested patients were positive for TBE. The highest incidence of EV infections was between 25 and 35 years and of HSV infections between 30 and 60 years. VZV infections had a bimodal distribution peaking below 30 and above 70 years. VZV and EV infections were more frequently observed during summer, whereas HSV infections showed no seasonal preference. Inflammatory changes in cerebrospinal fluid (CSF) were highest in HSV and lowest in EV infections. Polymerase chain reaction tests for HSV, VZV and EV in CSF and TBE serology determined the causative virus in over 60% of tested patients. The age of affected patients, seasonal distribution, disease course and inflammatory changes in CSF differ between groups of patients affected by the most common viral infections. © 2017 EAN.

Influence of Sex and Age on Natural Resistance to St. Louis Encephalitis Virus Infection in Mice

PubMed Central

Andersen, Arthur A.; Hanson, Robert P.

1974-01-01

A difference was observed in susceptibility of adult male and female mice to St. Louis encephalitis (SLE) virus as measured by the death rate after intravenous challenge. Female mice that had susceptibility similar to that of males at 2 months of age had increased resistance to SLE virus at 3 and 4 months of age. The increased resistance occurred after sexual maturity, indicating that the resistance factor possibly was related to an aging process in the female. The susceptibility of male mice remained unchanged over the 2- to 4-month period. Neither pregnancy nor castration had any effect on resistance of adult mice to St. Louis encephalitis virus. PMID:4857422

Nervous System Infections and the Global Traveler.

PubMed

Reid, Savina; Thompson, Haley; Thakur, Kiran T

2018-04-01

Neurological complications of infectious diseases are associated with high rates of morbidity and mortality. It is imperative that neurologists be up-to-date on current developments including typical and atypical presentations of neurological infections in travelers, diagnostic and treatment recommendations, and emerging pathogen resistance patterns to avoid fatal outcomes and long-term sequelae. This article will address concepts of emerging and reemerging infectious diseases, and will provide updates on the neurological manifestations of select emerging and reemerging infections, including Ebola virus, bacterial meningitis, enterovirus 71, Zika virus, cerebral malaria, and Japanese encephalitis. Emerging and reemerging neurotropic infectious diseases, including Zika virus, have recently been major global health threats. Factors contributing to the emergence of infectious diseases include closer contact with zoonoses, population growth in cities, globalization, environmental changes, and the rise in antibiotic resistance. Serotype replacement of bacterial meningitis, the possibility of viral persistence in the central nervous system in Ebola virus, antibiotic resistance of malaria, and the evolution of neurovirulent strains of Zika virus display some of the developing challenges that accompany various neurotropic infectious diseases. Neurologists should be aware of the factors contributing to the emergence and reemergence of neurotropic infectious diseases. As emerging and reemerging neurotropic infectious continue to be a major global health security threat, clinicians should be aware of the risks to travelers and current guidelines on prevention and management. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Research in drug development against viral diseases of military importance (biological testing). Volume 1. Final report, 15 November 1985-31 January 1991

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shannon, W.M.; Arnett, G.; Brazier, A.D.

1991-03-01

The purpose of this program is to evaluate the efficacy of candidate antiviral compounds against a spectrum of viruses of military importance. This program involves (a) primary testing of chemical compounds and natural products for antiviral efficacy in vitro using standard CPE-inhibition assays, (b) primary testing of compounds for antiviral efficacy in vivo in animal model systems, and (c) secondary evaluation of the active candidate antiviral compounds. The target viruses for in vitro testing are Vaccinia Virus (VV), Adenovirus (AD2), Vesicular Stomatitis Virus (VSV), Punta Toro Virus (PT), Sandfly Fever Virus (SF), Yellow Fever Virus (YF), Venezuelan Equine Encephalomyelitis Virusmore » (VE), Japanese Encephalitis Virus and Vaccinia Virus infections of mice. Approximately 10,000 compounds have been received for in vitro evaluation and over 66,000 assays have been performed on this contract. Compounds have been identified in nearly all virus systems that have confirmed antiviral activity equal or exceeding that of the various positive control compounds (Ribavirin, Selenazofurin, Carbocyclic-3-deaza-adenosine, Adenosine dialdehyde, Ara-A, ddC and AZT). Many of these compounds represent potent and selective new antiviral agents.« less

Human Antibody Responses to Emerging Mayaro Virus and Cocirculating Alphavirus Infections Examined by Using Structural Proteins from Nine New and Old World Lineages

PubMed Central

Smith, Jessica L.; Pugh, Christine L.; Cisney, Emily D.; Keasey, Sarah L.; Guevara, Carolina; Ampuero, Julia S.; Comach, Guillermo; Gomez, Doris; Ochoa-Diaz, Margarita; Hontz, Robert D.

2018-01-01

ABSTRACT Mayaro virus (MAYV), Venezuelan equine encephalitis virus (VEEV), and chikungunya virus (CHIKV) are vector-borne alphaviruses that cocirculate in South America. Human infections by these viruses are frequently underdiagnosed or misdiagnosed, especially in areas with high dengue virus endemicity. Disease may progress to debilitating arthralgia (MAYV, CHIKV), encephalitis (VEEV), and death. Few standardized serological assays exist for specific human alphavirus infection detection, and antigen cross-reactivity can be problematic. Therefore, serological platforms that aid in the specific detection of multiple alphavirus infections will greatly expand disease surveillance for these emerging infections. In this study, serum samples from South American patients with PCR- and/or isolation-confirmed infections caused by MAYV, VEEV, and CHIKV were examined by using a protein microarray assembled with recombinant capsid, envelope protein 1 (E1), and E2 from nine New and Old World alphaviruses. Notably, specific antibody recognition of E1 was observed only with MAYV infections, whereas E2 was specifically targeted by antibodies from all of the alphavirus infections investigated, with evidence of cross-reactivity to E2 of o’nyong-nyong virus only in CHIKV-infected patient serum samples. Our findings suggest that alphavirus structural protein microarrays can distinguish infections caused by MAYV, VEEV, and CHIKV and that this multiplexed serological platform could be useful for high-throughput disease surveillance. IMPORTANCE Mayaro, chikungunya, and Venezuelan equine encephalitis viruses are closely related alphaviruses that are spread by mosquitos, causing diseases that produce similar influenza-like symptoms or more severe illnesses. Moreover, alphavirus infection symptoms can be similar to those of dengue or Zika disease, leading to underreporting of cases and potential misdiagnoses. New methods that can be used to detect antibody responses to multiple alphaviruses within the same assay would greatly aid disease surveillance efforts. However, possible antibody cross-reactivity between viruses can reduce the quality of laboratory results. Our results demonstrate that antibody responses to multiple alphaviruses can be specifically quantified within the same assay by using selected recombinant protein antigens and further show that Mayaro virus infections result in unique responses to viral envelope proteins. PMID:29577083

Treatment of Venezuelan Equine Encephalitis Virus Infection with (-)-Carbodine

PubMed Central

Bowen, Richard A.; Rao, Jagadeeshwar R.; Day, Craig; Shafer, Kristiina; Smee, Donald F.; Morrey, John D.; Chu, Chung K.

2008-01-01

Venezuelan equine encephalitis virus (VEEV) may cause encephalitis in humans, for which no FDA-approved antiviral treatment is available. Carbocyclic cytosine (carbodine) has broad-spectrum activity but toxicity has limited its utility. It was anticipated that one of the enantiomers of carbodine would show enhanced activity and reduced toxicity. The activity of the D-(-) enantiomer of carbodine [(-)-carbodine] was evaluated by infectious cell culture assay and was found to have a 50% effective concentration (EC50) of 0.2 μg/ml against the TC-83 vaccine strain of VEEV in Vero cells, while the L-(+) enantiomer had no activity. Virus titer inhibition correlated with intracellular cytidine triphosphate reduction after treatment with (-)-carbodine, as determined by HPLC analysis. Pre-treatment with 200 mg/kg/d resulted in significant improvement in survival, virus load in the brain, weight change, and mean day to death in a mouse model of TC-83 VEEV disease. A single dose of (-)-Carbodine resulted in a slight extension of mean time to death in mice infected with wild-type VEEV. Post-virus exposure treatment with (-)-carbodine was effective in significantly improving disease parameters in mice infected with TC-83 VEEV when treatment was initiated as late as 4 days post-virus installation (dpi). It is remarkable that (-)-carbodine is effective when initiated after the establishment of brain infection. PMID:18675850

Research and Operational Support for the Study of Militarily Relevant Infectious Diseases of Interest to the United States Army and the Royal Thai Army

DTIC Science & Technology

2008-01-01

funding support for Royal Thai Army at Armed Forces Research Institute of Medical Sciences (AFRIMS) engaged in research activities in collaboration with... Active and Passive Protection of Mice against Japanese Encephalitis Virus 55 (a) Investigators 55 (b) Objectives 55 (c) Methods 55 (d) Results...Research Project: Sentinel Surveillance for Emerging Diseases Causing Dengue-like or Acute Encephalitis Syndrome in the Philippines (SEDP) 83 (a

West Nile virus and other arboviral diseases--United States, 2012.

PubMed

2013-06-28

Arthropod-borne viruses (arboviruses) are transmitted to humans primarily through the bites of infected mosquitoes and ticks. West Nile virus (WNV) is the leading cause of domestically acquired arboviral disease in the United States. However, several other arboviruses also cause sporadic cases and seasonal outbreaks of neuroinvasive disease (e.g., meningitis, encephalitis, and acute flaccid paralysis). In 2012, CDC received reports of 5,780 nationally notifiable arboviral disease cases (excluding dengue). A large multistate outbreak of WNV disease accounted for 5,674 (98%) of reported cases, the highest number reported since 2003. Other reported etiologies included Eastern equine encephalitis virus (EEEV), Powassan virus (POWV), St. Louis encephalitis virus (SLEV), and California serogroup viruses such as La Crosse virus (LACV) and Jamestown Canyon virus (JCV). Arboviruses continue to cause serious illness in substantial numbers of persons in the United States. Maintaining surveillance remains important to identify outbreaks and guide prevention efforts.

Vertical and horizontal transmission of tilapia larvae encephalitis virus: the bad and the ugly.

PubMed

Sinyakov, Michael S; Belotsky, Sandro; Shlapobersky, Mark; Avtalion, Ramy R

2011-02-05

Impairment of innate immunity in tilapia larvae after vertical and horizontal infection with the newly characterized tilapia larvae encephalitis virus (TLEV) was accessed by evaluation of cell-mediated reactive oxygen species (ROS) production in affected fish with the use of horseradish peroxidase-amplified luminol-dependent chemiluminescence assay. The priming in-vivo infection with TLEV resulted in downregulation of ROS response in both vertically- and horizontally-infected fish; this suppression was further exacerbated by specific in-vitro booster infection with the same virus. Application of Ca ionophore and phorbol myristate acetate as alternative nonspecific boosters enabled restoration of ROS release in vertically-infected but not in horizontally-infected larvae. The results indicate severe TLEV-imposed phagocyte dysfunction in affected larvae. The difference in restoration potential of ROS production after vertical and horizontal virus transmission is interpreted in the frame of principal distinctions between the two modes. Copyright © 2010 Elsevier Inc. All rights reserved.

Characterization of tick-borne encephalitis virus from Latvia.

PubMed

Mavtchoutko, V; Vene, S; Haglund, M; Forsgren, M; Duks, A; Kalnina, V; Hörling, J; Lundkvist, A

2000-02-01

Viruses of the tick-borne encephalitis (TBE) antigenic complex, within the family Flaviviridae, cause a variety of diseases including uncomplicated febrile illness, encephalitis, meningo-encephalitis, hemorrhagic fever and chronic disease in humans, domesticated animals or wildlife species. TBE is a serious problem in Latvia with up to a 1,000 patients confirmed serologically annually 1994-1995. No previous data had been reported on the causative agent of TBE in Latvia. In the present study, a virus was isolated from serum of a patient with clinical symptoms of an acute TBE infection. Nucleotide sequence information obtained by direct reverse transcription-polymerase chain reaction (RT-PCR) and the serological characteristics of the isolated virus strain, designated TBE-Latvia-1-96, indicated a closer relationship to the Vasilchenko strain, isolated in Novosibirsk (Siberia, Russia), as compared to the western European or far eastern subtypes of TBE viruses. In a mouse neurovirulence assay, a significant difference in survival rates (days) was shown between Latvia-1-96 and the western European TBE virus subtype. Copyright 2000 Wiley-Liss, Inc.

Blood-Brain Barrier Function and Biomarkers of Central Nervous System Injury in Rickettsial Versus Other Neurological Infections in Laos.

PubMed

Dittrich, Sabine; Sunyakumthorn, Piyanate; Rattanavong, Sayaphet; Phetsouvanh, Rattanaphone; Panyanivong, Phonepasith; Sengduangphachanh, Amphonsavanh; Phouminh, Phonelavanh; Anantatat, Tippawan; Chanthongthip, Anisone; Lee, Sue J; Dubot-Pérès, Audrey; Day, Nicholas P J; Paris, Daniel H; Newton, Paul N; Turner, Gareth D H

2015-08-01

Blood-brain barrier (BBB) function and cerebrospinal fluid (CSF) biomarkers were measured in patients admitted to hospital with severe neurological infections in the Lao People's Democratic Republic (N = 66), including bacterial meningitis (BM; N = 9) or tuberculosis meningitis (TBM; N = 11), Japanese encephalitis virus (JEV; N = 25), and rickettsial infections (N = 21) including murine and scrub typhus patients. The albumin index (AI) and glial fibrillary acidic protein (GFAP) levels were significantly higher in BM and TBM than other diseases but were also raised in individual rickettsial patients. Total tau protein was significantly raised in the CSF of JEV patients. No differences were found between clinical or neurological symptoms, AI, or biomarker levels that allowed distinction between severe neurological involvement by Orientia tsutsugamushi compared with Rickettsia species. © The American Society of Tropical Medicine and Hygiene.

Fatal Deer Tick Virus Infection in Maine.

PubMed

Cavanaugh, Catherine E; Muscat, Paul L; Telford, Sam R; Goethert, Heidi; Pendlebury, William; Elias, Susan P; Robich, Rebecca; Welch, Margret; Lubelczyk, Charles B; Smith, Robert P

2017-09-15

Deer tick virus (DTV), a genetic variant (lineage II) of Powassan virus, is a rare cause of encephalitis in North America. We report a fatal case of DTV encephalitis following a documented bite from an Ixodes scapularis tick and the erythema migrans rash associated with Lyme disease. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Morphological changes in human neural cells following tick-borne encephalitis virus infection.

PubMed

Růzek, Daniel; Vancová, Marie; Tesarová, Martina; Ahantarig, Arunee; Kopecký, Jan; Grubhoffer, Libor

2009-07-01

Tick-borne encephalitis (TBE) is one of the leading and most dangerous human viral neuroinfections in Europe and north-eastern Asia. The clinical manifestations include asymptomatic infections, fevers and debilitating encephalitis that might progress into chronic disease or fatal infection. To understand TBE pathology further in host nervous systems, three human neural cell lines, neuroblastoma, medulloblastoma and glioblastoma, were infected with TBE virus (TBEV). The susceptibility and virus-mediated cytopathic effect, including ultrastructural and apoptotic changes of the cells, were examined. All the neural cell lines tested were susceptible to TBEV infection. Interestingly, the neural cells produced about 100- to 10,000-fold higher virus titres than the conventional cell lines of extraneural origin, indicating the highly susceptible nature of neural cells to TBEV infection. The infection of medulloblastoma and glioblastoma cells was associated with a number of major morphological changes, including proliferation of membranes of the rough endoplasmic reticulum and extensive rearrangement of cytoskeletal structures. The TBEV-infected cells exhibited either necrotic or apoptotic morphological features. We observed ultrastructural apoptotic signs (condensation, margination and fragmentation of chromatin) and other alterations, such as vacuolation of the cytoplasm, dilatation of the endoplasmic reticulum cisternae and shrinkage of cells, accompanied by a high density of the cytoplasm. On the other hand, infected neuroblastoma cells did not exhibit proliferation of membranous structures. The virions were present in both the endoplasmic reticulum and the cytoplasm. Cells were dying preferentially by necrotic mechanisms rather than apoptosis. The neuropathological significance of these observations is discussed.

Arsenite-induced stress granule formation is inhibited by elevated levels of reduced glutathione in West Nile virus-infected cells

PubMed Central

Basu, Mausumi; Courtney, Sean C.

2017-01-01

Oxidative stress activates the cellular kinase HRI, which then phosphorylates eIF2α, resulting in stalled translation initiation and the formation of stress granules (SGs). SG assembly redirects cellular translation to stress response mRNAs and inhibits cap-dependent viral RNA translation. Flavivirus infections were previously reported to induce oxidative stress in infected cells but flavivirus-infected cells paradoxically develop resistance to arsenite (Ars)-induced SG formation with time after infection. This resistance was previously postulated to be due to sequestration of the SG protein Caprin1 by Japanese encephalitis virus capsid protein. However, Caprin1 did not co-localize with West Nile virus (WNV) capsid protein in infected cells. Other stressors induced SGs with equal efficiency in mock- and WNV-infected cells indicating the intrinsic ability of cells to assemble SGs was not disabled. Induction of both reactive oxygen species (ROS) and the antioxidant response was detected at early times after WNV-infection. The transcription factors, Nrf2 and ATF4, which activate antioxidant genes, were upregulated and translocated to the nucleus. Knockdown of Nrf2, ATF4 or apoptosis-inducing factor (AIF), a mitochondrial protein involved in regenerating intracellular reduced glutathione (GSH) levels, with siRNA or treatment of cells with buthionine sulphoximine, which induces oxidative stress by inhibiting GSH synthesis, decreased intracellular GSH levels and increased the number of SG-positive, infected cells. Mitochondria were protected from Ars-induced damage by WNV infection until late times in the infection cycle. The results indicate that the increase in virus-induced ROS levels is counterbalanced by a virus-induced antioxidant response that is sufficient to also overcome the increase in ROS induced by Ars treatment and prevent Ars-induced SG assembly and mitochondrial damage. The virus-induced alterations in the cellular redox status appear to provide benefits for the virus during its lifecycle. PMID:28241074

Genetic Determinants of Differential Oral Infection Phenotypes of West Nile and St. Louis Encephalitis Viruses in Culex spp. Mosquitoes

PubMed Central

Maharaj, Payal D.; Bolling, Bethany G.; Anishchenko, Michael; Reisen, William K.; Brault, Aaron C.

2014-01-01

St. Louis encephalitis virus (SLEV) has shown greater susceptibility to oral infectivity than West Nile virus (WNV) in Culex mosquitoes. To identify the viral genetic elements that modulate these disparate phenotypes, structural chimeras (WNV–pre-membrane [prM] and envelope [E] proteins [prME]/SLEV.IC (infectious clone) and SLEV-prME/WNV.IC) were constructed in which two of the structural proteins, the prM and E, were interchanged between viruses. Oral dose–response assessment with the chimeric/parental WNV and SLEV was performed to characterize the infection phenotypes in Culex mosquitoes by artificial blood meals. The median infectious dose required to infect 50% of Cx. quinquefasciatus with WNV was indistinguishable from that of the SLEV-prME/WNV.IC chimeric virus. Similarly, SLEV and WNV-prME/SLEV.IC virus exhibited an indistinguishable oral dose–response relationship in Cx. quinquefasciatus. Infection rates for WNV.IC and SLEV-prME/WNV.IC were significantly lower than SLEV.IC and WNV-prME/SLEV.IC infection rates. These results indicated that WNV and SLEV oral infectivities are not mediated by genetic differences within the prM and E proteins. PMID:25157120

Environmental and Biological Factors Influencing Culex pipiens quinquefasciatus Say (Diptera: Culicidae) Vector Competence for Saint Louis Encephalitis Virus

PubMed Central

Richards, Stephanie L.; Lord, Cynthia C.; Pesko, Kendra; Tabachnick, Walter J.

2009-01-01

Complex interactions between environmental and biological factors influence the susceptibility of Culex pipiens quinquefasciatus to St. Louis encephalitis virus and could affect the epidemiology of virus transmission. Similar interactions could have epidemiologic implications for other vector-virus systems. We conducted an experiment to examine four such factors in combination: mosquito age, extrinsic incubation temperature (EIT), virus dose, and colony. The proportion of mosquitoes with body infections or disseminated infections varied between colonies, and was dependant on age, EIT, and dose. We also show that the probability of a body or leg infection interacted in complex ways between colonies, ages, EITs, and doses. The complex interactive effects of environmental and biological factors must be taken into account for studies of vector competence and epidemiology, especially when laboratory studies are used to generalize to natural transmission dynamics where the extent of variation is largely unknown. PMID:19635881

Environmental and biological factors influencing Culex pipiens quinquefasciatus Say (Diptera: Culicidae) vector competence for Saint Louis encephalitis virus.

PubMed

Richards, Stephanie L; Lord, Cynthia C; Pesko, Kendra; Tabachnick, Walter J

2009-08-01

Complex interactions between environmental and biological factors influence the susceptibility of Culex pipiens quinquefasciatus to St. Louis encephalitis virus and could affect the epidemiology of virus transmission. Similar interactions could have epidemiologic implications for other vector-virus systems. We conducted an experiment to examine four such factors in combination: mosquito age, extrinsic incubation temperature (EIT), virus dose, and colony. The proportion of mosquitoes with body infections or disseminated infections varied between colonies, and was dependant on age, EIT, and dose. We also show that the probability of a body or leg infection interacted in complex ways between colonies, ages, EITs, and doses. The complex interactive effects of environmental and biological factors must be taken into account for studies of vector competence and epidemiology, especially when laboratory studies are used to generalize to natural transmission dynamics where the extent of variation is largely unknown.

Surveillance for Western equine encephalitis St. Louis encephalitis and West Nile viruses using reverse transcription loop-mediated isothermal amplification

DOE PAGES

Meagher, Robert J.; Ball, Cameron Scott; Langevin, Stanley A.; ...

2016-01-25

In this study, collection of mosquitoes and testing for vector-borne viruses is a key surveillance activity that directly influences the vector control efforts of public health agencies, including determining when and where to apply insecticides. Vector control districts in California routinely monitor for three human pathogenic viruses including West Nile virus (WNV), Western equine encephalitis virus (WEEV), and St. Louis encephalitis virus (SLEV). Reverse transcription quantitative polymerase chain reaction (RT-qPCR) offers highly sensitive and specific detection of these three viruses in a single multiplex reaction, but this technique requires costly, specialized equipment that is generally only available in centralized publicmore » health laboratories. We report the use of reverse transcription loop-mediated isothermal amplification (RT-LAMP) to detect WNV, WEEV, and SLEV RNA extracted from pooled mosquito samples collected in California, including novel primer sets for specific detection of WEEV and SLEV, targeting the nonstructural protein 4 (nsP4) gene of WEEV and the 3’ untranslated region (3’-UTR) of SLEV. Our WEEV and SLEV RT-LAMP primers allowed detection of <0.1 PFU/reaction of their respective targets in <30 minutes, and exhibited high specificity without cross reactivity when tested against a panel of alphaviruses and flaviviruses. Furthermore, the SLEV primers do not cross-react with WNV, despite both viruses being closely related members of the Japanese encephalitis virus complex. The SLEV and WEEV primers can also be combined in a single RT-LAMP reaction, with discrimination between amplicons by melt curve analysis. Although RT-qPCR is approximately one order of magnitude more sensitive than RT-LAMP for all three targets, the RT-LAMP technique is less instrumentally intensive than RT-qPCR and provides a more cost-effective method of vector-borne virus surveillance.« less

Tranylcypromine Reduces Herpes Simplex Virus 1 Infection in Mice

PubMed Central

Yao, Hui-Wen; Lin, Pin-Hung; Shen, Fang-Hsiu; Perng, Guey-Chuen; Tung, Yuk-Ying

2014-01-01

Herpes simplex virus 1 (HSV-1) infects the majority of the human population and establishes latency by maintaining viral genomes in neurons of sensory ganglia. Latent virus can undergo reactivation to cause recurrent infection. Both primary and recurrent infections can cause devastating diseases, including encephalitis and corneal blindness. Acyclovir is used to treat patients, but virus resistance to acyclovir is frequently reported. Recent in vitro findings reveal that pretreatment of cells with tranylcypromine (TCP), a drug widely used in the clinic to treat neurological disorders, restrains HSV-1 gene transcription by inhibiting the histone-modifying enzyme lysine-specific demethylase 1. The present study was designed to examine the anti-HSV-1 efficacy of TCP in vivo because of the paucity of reports on this issue. Using the murine model, we found that TCP decreased the severity of wild-type-virus-induced encephalitis and corneal blindness, infection with the acyclovir-resistant (thymidine kinase-negative) HSV-1 mutant, and tissue viral loads. Additionally, TCP blocked in vivo viral reactivation in trigeminal ganglia. These results support the therapeutic potential of TCP for controlling HSV-1 infection. PMID:24590478

Cellular Immune Responses to Live Attenuated Japanese Encephalitis (JE) Vaccine SA14-14-2 in Adults in a JE/Dengue Co-Endemic Area.

PubMed

Turtle, Lance; Tatullo, Filippo; Bali, Tanushka; Ravi, Vasanthapuram; Soni, Mohammed; Chan, Sajesh; Chib, Savita; Venkataswamy, Manjunatha M; Fadnis, Prachi; Yaïch, Mansour; Fernandez, Stefan; Klenerman, Paul; Satchidanandam, Vijaya; Solomon, Tom

2017-01-01

Japanese encephalitis (JE) virus (JEV) causes severe epidemic encephalitis across Asia, for which the live attenuated vaccine SA14-14-2 is being used increasingly. JEV is a flavivirus, and is closely related to dengue virus (DENV), which is co-endemic in many parts of Asia, with clinically relevant interactions. There is no information on the human T cell response to SA14-14-2, or whether responses to SA14-14-2 cross-react with DENV. We used live attenuated JE vaccine SA14-14-2 as a model for studying T cell responses to JEV infection in adults, and to determine whether these T cell responses are cross-reactive with DENV, and other flaviviruses. We conducted a single arm, open label clinical trial (registration: clinicaltrials.gov NCT01656200) to study T cell responses to SA14-14-2 in adults in South India, an area endemic for JE and dengue. Ten out of 16 (62.5%) participants seroconverted to JEV SA14-14-2, and geometric mean neutralising antibody (NAb) titre was 18.5. Proliferation responses were commonly present before vaccination in the absence of NAb, indicating a likely high degree of previous flavivirus exposure. Thirteen of 15 (87%) participants made T cell interferon-gamma (IFNγ) responses against JEV proteins. In four subjects tested, at least some T cell epitopes mapped cross-reacted with DENV and other flaviviruses. JEV SA14-14-2 was more immunogenic for T cell IFNγ than for NAb in adults in this JE/DENV co-endemic area. The proliferation positive, NAb negative combination may represent a new marker of long term immunity/exposure to JE. T cell responses can cross-react between JE vaccine and DENV in a co-endemic area, illustrating a need for greater knowledge on such responses to inform the development of next-generation vaccines effective against both diseases. clinicaltrials.gov (NCT01656200).

Nipah Virus Infection in Dogs, Malaysia, 1999

PubMed Central

Alim, Asiah N.M.; Bunning, Michel L.; Lee, Ong Bee; Wagoner, Kent D.; Amman, Brian R.; Stockton, Patrick C.; Ksiazek, Thomas G.

2009-01-01

The 1999 outbreak of Nipah virus encephalitis in humans and pigs in Peninsular Malaysia ended with the evacuation of humans and culling of pigs in the epidemic area. Serologic screening showed that, in the absence of infected pigs, dogs were not a secondary reservoir for Nipah virus. PMID:19523300

Systematic analysis of protein identity between Zika virus and other arthropod-borne viruses.

PubMed

Chang, Hsiao-Han; Huber, Roland G; Bond, Peter J; Grad, Yonatan H; Camerini, David; Maurer-Stroh, Sebastian; Lipsitch, Marc

2017-07-01

To analyse the proportions of protein identity between Zika virus and dengue, Japanese encephalitis, yellow fever, West Nile and chikungunya viruses as well as polymorphism between different Zika virus strains. We used published protein sequences for the Zika virus and obtained protein sequences for the other viruses from the National Center for Biotechnology Information (NCBI) protein database or the NCBI virus variation resource. We used BLASTP to find regions of identity between viruses. We quantified the identity between the Zika virus and each of the other viruses, as well as within-Zika virus polymorphism for all amino acid k -mers across the proteome, with k ranging from 6 to 100. We assessed accessibility of protein fragments by calculating the solvent accessible surface area for the envelope and nonstructural-1 (NS1) proteins. In total, we identified 294 Zika virus protein fragments with both low proportion of identity with other viruses and low levels of polymorphisms among Zika virus strains. The list includes protein fragments from all Zika virus proteins, except NS3. NS4A has the highest number (190 k -mers) of protein fragments on the list. We provide a candidate list of protein fragments that could be used when developing a sensitive and specific serological test to detect previous Zika virus infections.

Transient widespread cortical and splenial lesions in acute encephalitis/encephalopathy associated with primary Epstein-Barr virus infection.

PubMed

Zhang, Shuo; Feng, Juan; Shi, Yifang

2016-01-01

Infection with Epstein-Barr virus (EBV) is very common and usually occurs in childhood or early adulthood. Encephalitis/encephalopathy is an uncommon but serious neurological complication of EBV. A case of EBV-associated encephalitis/encephalopathy with involvement of reversible widespread cortical and splenial lesions is presented herein. An 8-year-old Chinese girl who presented with fever and headache, followed by seizures and drowsiness, was admitted to the hospital. Magnetic resonance imaging revealed high signal intensities on diffusion-weighted imaging in widespread cortical and splenial lesions. The clinical and laboratory examination results together with the unusual radiology findings suggested acute encephalitis/encephalopathy due to primary EBV infection. After methylprednisolone pulse therapy together with ganciclovir, the patient made a full recovery without any brain lesions. The hallmark clinical-radiological features of this patient included severe encephalitis/encephalopathy at onset, the prompt and complete recovery, and rapidly reversible widespread involvement of the cortex and splenium. Patients with EBV encephalitis/encephalopathy who have multiple lesions, even with the widespread involvement of cortex and splenium of the corpus callosum, may have a favorable outcome with complete disappearance of all brain lesions. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Human and Equine Infection with Alphaviruses and Flaviviruses in Panamá during 2010: A Cross-Sectional Study of Household Contacts during an Encephalitis Outbreak.

PubMed

Carrera, Jean-Paul; Bagamian, Karoun H; Travassos da Rosa, Amelia P; Wang, Eryu; Beltran, Davis; Gundaker, Nathan D; Armien, Blas; Arroyo, Gianfranco; Sosa, Néstor; Pascale, Juan Miguel; Valderrama, Anayansi; Tesh, Robert B; Vittor, Amy Y; Weaver, Scott C

2018-06-01

Members of the genera Alphavirus (family Togaviridae ) and Flavivirus (family Flaviridae ) are important zoonotic human and equine etiologic agents of neurologic diseases in the New World. In 2010, an outbreak of Madariaga virus (MADV; formerly eastern equine encephalitis virus) and Venezuelan equine encephalitis virus (VEEV) infections was reported in eastern Panamá. We further characterized the epidemiology of the outbreak by studying household contacts of confirmed human cases and of equine cases with neurological disease signs. Serum samples were screened using a hemagglutination inhibition test, and human results were confirmed using plaque reduction neutralization tests. A generalized linear model was used to evaluate the human MADV and VEEV seroprevalence ratios by age (in tercile) and gender. Overall, antibody prevalence for human MADV infection was 19.4%, VEEV 33.3%, and Mayaro virus 1.4%. In comparison with individuals aged 2-20 years, people from older age groups (21-41 and > 41 years) were five times more likely to have antibodies against VEEV, whereas the MADV prevalence ratio was independent of age. The overall seroprevalence of MADV in equids was 26.3%, VEEV 29.4%, West Nile virus (WNV) 2.6%, and St. Louis encephalitis virus (SLEV) was 63.0%. Taken together, our results suggest that multiple arboviruses are circulating in human and equine populations in Panamá. Our findings of a lack of increase in the seroprevalence ratio with age support the hypothesis of recent MADV exposure to people living in the affected region.

Cerebrospinal fluid biomarkers of simian immunodeficiency virus encephalitis

PubMed Central

Bissel, Stephanie J.; Kofler, Julia; Nyaundi, Julia; Murphey-Corb, Michael; Wisniewski, Stephen R.; Wiley, Clayton A.

2016-01-01

Antiretroviral therapy has led to increased survival of HIV-infected patients but also increased prevalence of HIV-associated neurocognitive disorders. We previously identified YKL40 as a potential cerebrospinal fluid (CSF) biomarker of lentiviral central nervous system (CNS) disease in HIV-infected patients and in the macaque model of HIV encephalitis. The aim of this study was to define the specificity and sensitivity along with the predictive value of YKL40 as a biomarker of encephalitis and to assess its relationship to CSF viral load. CSF YKL40 and SIV RNA concentrations were analyzed over the course of infection in 19 SIV-infected pigtailed macaques and statistical analyses were performed to evaluate the relationship to encephalitis. Using these relationships, CSF alterations of 31 neuroimmune markers were studied pre-infection, during acute and asymptomatic infection, at the onset of encephalitis, and at necropsy. YKL40 CSF concentrations above 1122 ng/ml were found to be a specific and sensitive biomarker for the presence of encephalitis and were highly correlated with CSF viral load. Macaques that developed encephalitis had evidence of chronic CNS immune activation during early, asymptomatic, and end stages of infection. At the onset of encephalitis, CSF demonstrated a rise of neuroimmune markers associated with macrophage recruitment, activation and interferon response. CSF YKL40 concentration and viral load are valuable biomarkers to define the onset of encephalitis. Chronic CNS immune activation precedes the development of encephalitis while some responses suggest protection from CNS lentiviral disease. PMID:27059917

History of Mosquitoborne Diseases in the United States and Implications for New Pathogens.

PubMed

Moreno-Madriñán, Max J; Turell, Michael

2018-05-01

The introduction and spread of West Nile virus and the recent introduction of chikungunya and Zika viruses into the Americas have raised concern about the potential for various tropical pathogens to become established in North America. A historical analysis of yellow fever and malaria incidences in the United States suggests that it is not merely a temperate climate that keeps these pathogens from becoming established. Instead, socioeconomic changes are the most likely explanation for why these pathogens essentially disappeared from the United States yet remain a problem in tropical areas. In contrast to these anthroponotic pathogens that require humans in their transmission cycle, zoonotic pathogens are only slightly affected by socioeconomic factors, which is why West Nile virus became established in North America. In light of increasing globalization, we need to be concerned about the introduction of pathogens such as Rift Valley fever, Japanese encephalitis, and Venezuelan equine encephalitis viruses.

BK virus encephalitis with thrombotic microangiopathy in an allogeneic hematopoietic stem cell transplant recipient.

PubMed

Lopes da Silva, R; Ferreira, I; Teixeira, G; Cordeiro, D; Mafra, M; Costa, I; Bravo Marques, J M; Abecasis, M

2011-04-01

BK virus (BKV) infection occurs most often in immunocompromised hosts, in the setting of renal or bone marrow transplantation. Hemorrhagic cystitis is the commonest manifestation but in recent years infections in other organ systems have been reported. We report an unusual case of biopsy-proven BKV encephalitis in a hematopoietic stem cell transplant patient who subsequently developed thrombotic microangiopathy. As far as we know, this is the first report of such an association in a transplant patient. © 2010 John Wiley & Sons A/S.

Laser Capture Microdissection Assessment of Virus Compartmentalization in the Central Nervous Systems of Macaques Infected with Neurovirulent Simian Immunodeficiency Virus

PubMed Central

Matsuda, Kenta; Brown, Charles R.; Foley, Brian; Goeken, Robert; Whitted, Sonya; Dang, Que; Wu, Fan; Plishka, Ronald; Buckler-White, Alicia

2013-01-01

Nonhuman primate-simian immunodeficiency virus (SIV) models are powerful tools for studying the pathogenesis of human immunodeficiency virus type 1 (HIV-1) in the brain. Our laboratory recently isolated a neuropathogenic viral swarm, SIVsmH804E, a derivative of SIVsmE543-3, which was the result of sequential intravenous passages of viruses isolated from the brains of rhesus macaques with SIV encephalitis. Animals infected with SIVsmH804E or its precursor (SIVsmH783Br) developed SIV meningitis and/or encephalitis at high frequencies. Since we observed macaques with a combination of meningitis and encephalitis, as well as animals in which meningitis or encephalitis was the dominant component, we hypothesized that distinct mechanisms could be driving the two pathological states. Therefore, we assessed viral populations in the meninges and the brain parenchyma by laser capture microdissection. Viral RNAs were isolated from representative areas of the meninges, brain parenchyma, terminal plasma, and cerebrospinal fluid (CSF) and from the inoculum, and the SIV envelope fragment was amplified by PCR. Phylogenetic analysis of envelope sequences from the conventional progressors revealed compartmentalization of viral populations between the meninges and the parenchyma. In one of these animals, viral populations in meninges were closely related to those from CSF and shared signature truncations in the cytoplasmic domain of gp41, consistent with a common origin. Apart from magnetic resonance imaging (MRI) and positron-emission tomography (PET) imaging, CSF is the most accessible assess to the central nervous system for HIV-1-infected patients. However, our results suggest that the virus in the CSF may not always be representative of viral populations in the brain and that caution should be applied in extrapolating between the properties of viruses in these two compartments. PMID:23720733

Cytokine Protein Expression Levels in Tracheobronchial Lymph Node Homogenates of Pigs Infected with Pseudorabies Virus

USDA-ARS?s Scientific Manuscript database

Pseudorabies virus (PRV) is a neurotropic alphaherpesvirus that produces fatal encephalitis in newborn pigs, respiratory disorders in fattening pigs and reproductive failure in sows. Following primary infection of the respiratory tract, PRV can develop into a systemic infection with dispersion of t...

Phase III Clinical Trials Comparing the Immunogenicity and Safety of the Vero Cell-Derived Japanese Encephalitis Vaccine Encevac with Those of Mouse Brain-Derived Vaccine by Using the Beijing-1 Strain

PubMed Central

Miyazaki, Chiaki; Okada, Kenji; Ozaki, Takao; Hirose, Mizuo; Iribe, Kaneshige; Ishikawa, Yuji; Togashi, Takehiro; Ueda, Kohji

2014-01-01

The immunogenicity and safety of an inactivated cell culture Japanese encephalitis vaccine (CC-JEV) were compared with those of an inactivated mouse brain-derived Japanese encephalitis vaccine (MB-JEV) in phase III clinical multicenter trials conducted in children. The vaccines contain the same Japanese encephalitis virus strain, the Beijing-1 strain. Two independent clinical trials (trials 1 and 2) were conducted. Trial 1 was conducted in 468 healthy children. Each subject was injected with 17 μg per dose of either CC-JEV or MB-JEV, and the immunogenicity and safety of the vaccines were investigated. Trial 1 showed that CC-JEV was more immunogenic and reactive than MB-JEV at the same dose. Therefore, to adjust the immunogenicity of CC-JEV to that of MB-JEV, a vaccine that has had a good track record regarding its efficacy for a long time, trial 2 was conducted in 484 healthy children. To improve the stability, CC-JEV was converted from a liquid type to a freeze-dried type of vaccine. Each subject was injected subcutaneously with either 4 μg per dose of CC-JEV, 8 μg per dose of CC-JEV, or 17 μg per dose of MB-JEV twice, at an interval of 2 to 4 weeks, followed by an additional booster immunization 1 to 15 months after the primary immunization. Based on the results of trial 2, 4 μg per dose of the freeze-dried CC-JEV (under the label Encevac) was selected as a substitute for the MB-JEV. Encevac was approved and launched in 2011 and has since been in use as a 2nd-generation Japanese encephalitis vaccine in Japan. (These studies have been registered at the JapicCTI under registration no. JapicCTI-132063 and JapicCTI-080586 for trials 1 and 2, respectively.) PMID:24334689

Autophagy interaction with herpes simplex virus type-1 infection

PubMed Central

O'Connell, Douglas; Liang, Chengyu

2016-01-01

abstract More than 50% of the U.S. population is infected with herpes simplex virus type-I (HSV-1) and global infectious estimates are nearly 90%. HSV-1 is normally seen as a harmless virus but debilitating diseases can arise, including encephalitis and ocular diseases. HSV-1 is unique in that it can undermine host defenses and establish lifelong infection in neurons. Viral reactivation from latency may allow HSV-1 to lay siege to the brain (Herpes encephalitis). Recent advances maintain that HSV-1 proteins act to suppress and/or control the lysosome-dependent degradation pathway of macroautophagy (hereafter autophagy) and consequently, in neurons, may be coupled with the advancement of HSV-1-associated pathogenesis. Furthermore, increasing evidence suggests that HSV-1 infection may constitute a gradual risk factor for neurodegenerative disorders. The relationship between HSV-1 infection and autophagy manipulation combined with neuropathogenesis may be intimately intertwined demanding further investigation. PMID:26934628

Cyclophilin B facilitates the replication of Orf virus.

PubMed

Zhao, Kui; Li, Jida; He, Wenqi; Song, Deguang; Zhang, Ximu; Zhang, Di; Zhou, Yanlong; Gao, Feng

2017-06-15

Viruses interact with host cellular factors to construct a more favourable environment for their efficient replication. Expression of cyclophilin B (CypB), a cellular peptidyl-prolyl cis-trans isomerase (PPIase), was found to be significantly up-regulated. Recently, a number of studies have shown that CypB is important in the replication of several viruses, including Japanese encephalitis virus (JEV), hepatitis C virus (HCV) and human papillomavirus type 16 (HPV 16). However, the function of cellular CypB in ORFV replication has not yet been explored. Suppression subtractive hybridization (SSH) technique was applied to identify genes differentially expressed in the ORFV-infected MDBK cells at an early phase of infection. Cellular CypB was confirmed to be significantly up-regulated by quantitative reverse transcription-PCR (qRT-PCR) analysis and Western blotting. The role of CypB in ORFV infection was further determined using Cyclosporin A (CsA) and RNA interference (RNAi). Effect of CypB gene silencing on ORFV replication by 50% tissue culture infectious dose (TCID 50 ) assay and qRT-PCR detection. In the present study, CypB was found to be significantly up-regulated in the ORFV-infected MDBK cells at an early phase of infection. Cyclosporin A (CsA) exhibited suppressive effects on ORFV replication through the inhibition of CypB. Silencing of CypB gene inhibited the replication of ORFV in MDBK cells. In conclusion, these data suggest that CypB is critical for the efficient replication of the ORFV genome. Cellular CypB was confirmed to be significantly up-regulated in the ORFV-infected MDBK cells at an early phase of infection, which could effectively facilitate the replication of ORFV.

A New Model for Hendra Virus Encephalitis in the Mouse

PubMed Central

Dups, Johanna; Middleton, Deborah; Yamada, Manabu; Monaghan, Paul; Long, Fenella; Robinson, Rachel; Marsh, Glenn A.; Wang, Lin-Fa

2012-01-01

Hendra virus (HeV) infection in humans is characterized by an influenza like illness, which may progress to pneumonia or encephalitis and lead to death. The pathogenesis of HeV infection is poorly understood, and the lack of a mouse model has limited the opportunities for pathogenetic research. In this project we reassessed the role of mice as an animal model for HeV infection and found that mice are susceptible to HeV infection after intranasal exposure, with aged mice reliably developing encephalitic disease. We propose an anterograde route of neuroinvasion to the brain, possibly along olfactory nerves. This is supported by evidence for the development of encephalitis in the absence of viremia and the sequential distribution of viral antigen along pathways of olfaction in the brain of intranasally challenged animals. In our studies mice developed transient lower respiratory tract infection without progressing to viremia and systemic vasculitis that is common to other animal models. These studies report a new animal model of HeV encephalitis that will allow more detailed studies of the neuropathogenesis of HeV infection, particularly the mode of viral spread and possible sequestration within the central nervous system; investigation of mechanisms that moderate the development of viremia and systemic disease; and inform the development of improved treatment options for human patients. PMID:22808132

[Acute encephalitis. Neuropsychiatric manifestations as expression of influenza virus infection].

PubMed

Moreno-Flagge, Noris; Bayard, Vicente; Quirós, Evelia; Alonso, Tomás

2009-01-01

The aim is to review the encephalitis in infants and adolescents as well as its etiology, clinical manifestation, epidemiology, physiopathology, diagnostic methods and treatment, and the neuropsyquiatric signs appearing an influenza epidemy. Encephalitis is an inflammation of the central nervous system (CNS) which involves the brain. The clinical manifestations usually are: headache, fever and confusional stage. It could also be manifested as seizures, personality changes, or psiqyiatric symptoms. The clinical manifestations are related to the virus and the cell type affected in the brain. A meningitis or encephalopathy need to be ruled out. It could be present as an epidemic or isolated form, beeing this the most frequent form. It could be produced by a great variety of infections agents including virus, bacterias, fungal and parasitic. Viral causes are herpesvirus, arbovirus, rabies and enterovirus. Bacterias such as Borrelia burgdorferi, Rickettsia and Mycoplasma neumoniae. Some fungal causes are: Coccidioides immitis and Histoplasma capsulatum. More than 100 agents are related to encephalitis. The diagnosis of encephalitis is a challenge for the clinician and its infectious etiology is clear in only 40 to 70% of all cases. The diagnosis of encephalitis can be established with absolute certainty only by the microscopic examination of brain tissue. Epidemiology is related to age of the patients, geographic area, season, weather or the host immune system. Early intervention can reduce the mortality rate and sequels. We describe four patients with encephalitis and neuropsychiatric symptoms during an influenza epidemic.

Venezuelan equine encephalitis virus infection causes modulation of inflammatory and immune response genes in mouse brain

PubMed Central

Sharma, Anuj; Bhattacharya, Bhaskar; Puri, Raj K; Maheshwari, Radha K

2008-01-01

Background Neurovirulent Venezuelan equine encephalitis virus (VEEV) causes lethal encephalitis in equines and is transmitted to humans by mosquitoes. VEEV is highly infectious when transmitted by aerosol and has been developed as a bio-warfare agent, making it an important pathogen to study from a military and civilian standpoint. Molecular mechanisms of VEE pathogenesis are poorly understood. To study these, the gene expression profile of VEEV infected mouse brains was investigated. Changes in gene expression were correlated with histological changes in the brain. In addition, a molecular framework of changes in gene expression associated with progression of the disease was studied. Results Our results demonstrate that genes related to important immune pathways such as antigen presentation, inflammation, apoptosis and response to virus (Cxcl10, CxCl11, Ccl5, Ifr7, Ifi27 Oas1b, Fcerg1,Mif, Clusterin and MHC class II) were upregulated as a result of virus infection. The number of over-expressed genes (>1.5-fold level) increased as the disease progressed (from 197, 296, 400, to 1086 at 24, 48, 72 and 96 hours post infection, respectively). Conclusion Identification of differentially expressed genes in brain will help in the understanding of VEEV-induced pathogenesis and selection of biomarkers for diagnosis and targeted therapy of VEEV-induced neurodegeneration. PMID:18558011

Development of an anti-dengue NS1 IgG ELISA to evaluate exposure to dengue virus.

PubMed

Nascimento, Eduardo J M; George, James K; Velasco, Melissa; Bonaparte, Matthew I; Zheng, Lingyi; DiazGranados, Carlos A; Marques, Ernesto T A; Huleatt, James W

2018-07-01

Dengue virus infection elicits immune responses to multiple viral antigens including antibodies to dengue non-structural protein 1 (NS1) which are rapidly induced and detected within days of infection. The recombinant, live, attenuated, tetravalent dengue vaccine (CYD-TDV; Sanofi Pasteur) uses the yellow fever vaccine virus as a back-bone but expresses dengue virus pre-membrane and envelop proteins. Since CYD-TDV does not express dengue NS1, we evaluated the utility of dengue NS1-specific IgG antibodies as biomarkers of dengue exposure in CYD-TDV recipients and controls. We optimized and evaluated a quantitative anti-dengue NS1 IgG enzyme-linked immunosorbent assay (ELISA). Parameters assessed included: accuracy, dilutability/linearity, precision, limit of quantitation and specificity. The assay specificity was further evaluated using Japanese Encephalitis virus, West Nile virus, Yellow Fever virus or Zika virus positive sera samples collected following confirmed infection or vaccination. Receiver-operating-characteristics (ROC) curves as well as sensitivity and specificity for discriminating previous dengue exposure were assessed using 1250 reference samples. Overall, the anti-dengue NS1 IgG ELISA was able to discriminate previous dengue exposure from non-exposure before vaccination with CYD-TDV (ROC area under the curve > 0.9). Assessment of paired samples from 2511 vaccinated participants showed high overall agreement (93%) between pre-vaccination and post-vaccination dengue serostatus classification based on the anti-dengue NS1 IgG ELISA. However, misclassification of dengue serostatus was observed after vaccination likely due to a combination of asymptomatic dengue infections, assay variability and a modest effect of CYD-TDV on the anti-dengue NS1 IgG ELISA readout. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Present and Future Arboviral Threats

PubMed Central

Weaver, Scott C.; Reisen, William K.

2009-01-01

Arthropod-borne viruses (arboviruses) are important causes of human disease nearly worldwide. All arboviruses circulate among wild animals, and many cause disease after spillover transmission to humans and agriculturally important domestic animals that are incidental or dead-end hosts. Viruses such as dengue (DENV) and chikungunya (CHIKV) viruses that have lost the requirement for enzootic amplification now produce extensive epidemics in tropical urban centers. Many arboviruses recently have increased in importance as human and veterinary pathogens using a variety of mechanisms. Beginning in 1999, West Nile virus (WNV) underwent a dramatic geographic expansion into the Americas. High amplification associated with avian virulence coupled with adaptation for replication at higher temperatures in mosquito vectors, it has caused the largest epidemic of arboviral encephalitis ever reported in the Americas. Japanese encephalitis virus (JEV), the most frequent arboviral cause of encephalitis worldwide, has spread throughout most of Asia and as far south as Australia from its putative origin in Indonesia and Malaysia. JEV has caused major epidemics as it invaded new areas, often enabled by rice culture and amplification in domesticated swine. Rift Valley fever virus (RVFV), another arbovirus that infects humans after amplification in domesticated animals, undergoes epizootic transmission during wet years following droughts. Warming of the Indian Ocean, linked to the El Niño-Southern Oscillation in the Pacific, leads to heavy rainfall in east Africa inundating surface pools and vertically-infected mosquito eggs laid during previous seasons. Like WNV, JEV and RVFV could become epizootic and epidemic in the Americas if introduced unintentionally via commerce or intentionally for nefarious purposes. Climate warming also could facilitate the expansion of the distributions of many arboviruses, as documented for bluetongue viruses (BTV), major pathogens of ruminants. BTV, especially BTV-8, invaded Europe after climate warming enabled the major midge vector to expand is distribution northward into southern Europe and extended the transmission season and vectorial capacity of local midge species. Perhaps the greatest health risk of arboviral emergence comes from extensive tropical urbanization and the colonization of this expanding habitat by the highly anthropophilic (attracted to humans) mosquito, Aedes aegypti. These factors led to the emergence of permanent endemic cycles of urban DENV and chikungunya virus (CHIKV), as well as seasonal interhuman transmission of yellow fever and Zika viruses. The recent invasion into the Americas, Europe and Africa of Ae. albopictus, an important CHIKV and secondary DENV vector, could enhance urban transmission of these viruses in tropical as well as temperate regions. The minimal requirements for sustained endemic arbovirus transmission, adequate human viremia and vector competence of Ae. aegypti and/or Ae. albopictus, may be met by two other viruses with the potential to become major human pathogens: Venezuelan equine encephalitis virus, already an important cause of neurological disease in humans and equids throughout the Americas, and Mayaro virus, a close relative of CHIKV that produces a comparably debilitating arthralgic disease in South America. Further research is needed to understand the potential of these and other arboviruses to emerge in the future, invade new geographic areas, and become important public and veterinary health problems. PMID:19857523

[Analysis of pathogen spectrum of Encephalitis/Meningitis in northwestern area of China].

PubMed

Zhang, Xiao-shu; Wang, Xu-xia; Yu, De-shan; Jiang, Jian-xiang; Zhang, Guang-ye; Wang, Fang; Li, Hui

2013-10-01

To learn the characteristics of pathogen spectrum of Encephalitis /Meningitis in northwestern area of China. Between January 1st 2009 and March 31st 2011, a total of 569 patients with clinical symptoms of Encephalitis/Meningitis were selected from the hospitals in Gansu, Qinghai,Inner Mongolia and Xinjiang province. 1514 samples of specimen were collected from the 515 patients, to detect the IgM of Japanese encephalitis virus (JEV), enterovirus (EV, including Coxsackie virus, ECHO virus and enterovirus 71), Mumps virus, Herpes simplex virus (HSV) in blood and cerebrospinal fluid. Meanwhile, Neisseria meningitis (Nm), Haemophilus influenzae Type B (Hib), Staphylococcus, Streptococcus pneumonia, Streptococcus Suis, E. Coli and Cryptococci were also identified. The detection results were analyzed by different region, time and age range. Pathogenic bacteria were identified in the specimen from 16 patients, with the rate at 3.65%, of which the dominant ones were Streptococcus pneumonia (7 patients, 43.75%). Virus were identified in the specimen from 132 patients, with the rate at 27.05%, of which the dominant types were EV and HSV, accounting for 33.33% (44 cases) and 31.82% (42 cases) respectively. The detection rate of virus showed a significant seasonal trend, with the peak appearing between June and November each year. The peak of EV detection was between July and September, with 24 cases detected out; the peak of HSV was between June and August (11 cases detected out); mumps virus was mainly found between July and December (25 cases). There was no significant time-distribution found in the detection of bacteria. The EV and HSV were mainly distributed in Gansu and Qinghai province (70 cases) ;most of mumps virus were found in Gansu province (24 cases);and JEV were only found in Gansu province (20 cases). The viral pathogen spectrum was identified in all ages, and the EV and mumps virus were mainly found in children aged 0-14 years old (42 and 17 cases respectively) ; JEV were identified in people over 15 years old, with 13 detected out of the 20 patients. The main pathogen of acute encephalitis and meningitis in northwestern area of China was virus, and the main pathogens of encephalitis and meningitis in children under 15 years were Herpes simplex virus and Mumps virus.

Powassan virus infection presenting as acute disseminated encephalomyelitis in Tennessee.

PubMed

Hicar, Mark D; Edwards, Kathryn; Bloch, Karen

2011-01-01

Powassan virus is a rarely diagnosed cause of encephalitis, and is associated with significant neurologic sequelae. Although symptomatic infections with Powassan virus occur primarily in adults, we report a case of confirmed Powassan neuroinvasive disease in a child presenting to a Tennessee hospital, with symptoms and imaging studies suggestive of acute disseminated encephalomyelitis.

Genetic Profiling and Comorbidities of Zika Infection.

PubMed

Moni, Mohammad Ali; Lio', Pietro

2017-09-15

The difficulty in distinguishing infection by Zika virus (ZIKV) from other flaviviruses is a global health concern, particularly given the high risk of neurologic complications (including Guillain-Barré syndrome [GBS]) with ZIKV infection. We developed quantitative frameworks to compare and explore infectome, diseasome, and comorbidity of ZIKV infections. We analyzed gene expression microarray and RNA-Seq data from ZIKV, West Nile fever (WNF), chikungunya, dengue, yellow fever, Japanese encephalitis virus, GBS, and control datasets. Using neighborhood-based benchmarking and multilayer network topology, we constructed relationship networks based on the Online Mendelian Inheritance in Man database and our identified significant genes. ZIKV infections showed dysregulation in expression of 929 genes. Forty-seven genes were highly expressed in both ZIKV and dengue infections. However, ZIKV shared <15 significant transcripts with other flavivirus infections. Notably, dysregulation of MAFB and SELENBP1 was common to ZIKV, dengue, and GBS infection; ATF5, TNFAIP3, and BAMB1 were common to ZIKV, dengue, and WNF; and NAMPT and PMAlP1 were common to ZIKV, GBS, and WNF. Phylogenetic, ontologic, and pathway analyses showed that ZIKV infection most resembles dengue fever. We have developed methodologies to investigate disease mechanisms and predictions for infectome, diseasome, and comorbidities quantitatively, and identified particular similarities between ZIKV and dengue infections. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Tick-borne encephalitis: A review of epidemiology, clinical characteristics, and management

PubMed Central

Bogovic, Petra; Strle, Franc

2015-01-01

Tick-borne encephalitis is an infection of central nervous system caused by tick-borne encephalitis virus transmitted to humans predominantly by tick bites. During the last few decades the incidence of the disease has been increasing and poses a growing health problem in almost all endemic European and Asian countries. Most cases occur during the highest period of tick activity, in Central Europe mainly from April to November. Tick-borne encephalitis is more common in adults than in children. Clinical spectrum of the disease ranges from mild meningitis to severe meningoencephalitis with or without paralysis. Rare clinical manifestations are an abortive form of the disease and a chronic progressive form. A post-encephalitic syndrome, causing long-lasting morbidity that often affects the quality of life develops in up to 50% of patients after acute tick-borne encephalitis. Clinical course and outcome vary by subtype of tick-borne encephalitis virus (the disease caused by the European subtype has milder course and better outcome than the disease caused by Siberian and Far-Easter subtypes), age of patients (increasing age is associated with less favorable outcome), and host genetic factors. Since clinical features and laboratory results of blood and cerebrospinal fluid are nonspecific, the diagnosis must be confirmed by microbiologic findings. The routine laboratory confirmation of the tick-borne encephalitis virus infection is based mainly on the detection of specific IgM and IgG antibodies in serum (and cerebrospinal fluid), usually by enzyme-linked immunosorbent assay. There is no specific antiviral treatment for tick-borne encephalitis. Vaccination can effectively prevent the disease and is indicated for persons living in or visiting tick-borne encephalitis endemic areas. PMID:25984517

Development of a human live attenuated West Nile infectious DNA vaccine: Suitability of attenuating mutations found in SA14-14-2 for WN vaccine design

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yamshchikov, Vladimir, E-mail: yaximik@gmail.com; Manuvakhova, Marina; Rodriguez, Efrain

Direct attenuation of West Nile (WN) virus strain NY99 for the purpose of vaccine development is not feasible due to its high virulence and pathogenicity. Instead, we created highly attenuated chimeric virus W1806 with the serological identity of NY99. To further attenuate W1806, we investigated effects of mutations found in Japanese encephalitis virus vaccine SA14-14-2. WN viruses carrying all attenuating mutations lost infectivity in mammalian, but not in mosquito cells. No single reversion restored infectivity in mammalian cells, although increased infectivity in mosquito cells was observed. To identify a subset of mutations suitable for further attenuation of W1806, we analyzedmore » effects of E{sub 138}K and K{sub 279}M changes on virulence, growth properties, and immunogenicity of derivatized W956, from which chimeric W1806 inherited its biological properties and attenuation profile. Despite strong dominant attenuating effect, introduction of only two mutations was not sufficient for attenuating W1806 to the safety level acceptable for human use. - Highlights: • Further attenuation of a WN vaccine precursor is outlined. • Effect of SA14-14-2 attenuating mutations is tested. • Mechanism of attenuation is proposed and illustrated. • The need for additional attenuating mutations is justified.« less

Japanese Encephalitis Virus Immunoglobulin M Antibodies in Porcine Sera

DTIC Science & Technology

1985-10-01

units of other prototype flavivirus suckling mouse brain antigens were used: 2.0 0 0 00 Wesselsbron, Langat , Tembusu, and Dengue type 2. which are o all...strongly reactive :. sentinel pig sera and all 7 positive abattoir sera were Discussion • . retested, using Wesselsbron, Langat , Tembusu, or Den

Herpes simplex and varicella zoster CNS infections: clinical presentations, treatments and outcomes.

PubMed

Kaewpoowat, Quanhathai; Salazar, Lucrecia; Aguilera, Elizabeth; Wootton, Susan H; Hasbun, Rodrigo

2016-06-01

To describe the clinical manifestations, cerebrospinal fluid (CSF) characteristics, imaging studies and prognostic factors of adverse clinical outcomes (ACO) among adults with herpes simplex virus (HSV) or varicella zoster virus (VZV) CNS infections. Retrospective review of adult patients with positive HSV or VZV polymerase chain reaction on CSF from an observational study of meningitis or encephalitis in Houston, TX (2004-2014), and New Orleans, LA (1999-2008). Ninety-eight adults patients were identified; 25 had encephalitis [20 (20.4 %) HSV, 5 (5.1 %) VZV], and 73 had meningitis [60 (61.1 %) HSV and 13 (13.3 %) VZV]. HSV and VZV had similar presentations except for nausea (P < 0.01) and rash (P < 0.001). The CSF profile did not differ between HSV and VZV infection. Abnormal neuroimaging findings were found in 11.6 % (10/86) brain CTs and 21.3 % (16/75) brain MRIs. The EEG was abnormal in 57.9 % (11/19). Sixteen patients (16.3 %) had an ACO (10 HSV encephalitis, 3 VZV encephalitis and 3 VZV meningitis). Intravenous acyclovir administered within 48 h was protective against an ACO [OR 0.19 (0.04-0.80), P = 0.02). However, on logistic regression only Charlson comorbidity score >1 and an encephalitis presentation were independently associated with an ACO. The treatment for HSV meningitis was variable, and all patients had a good clinical outcome. Alpha herpes CNS infections due to HSV and VZV infections have similar clinical and laboratory manifestations. ACO was observed more frequently in those patients with comorbidities and an encephalitis presentation.

Viruses in reptiles

PubMed Central

2011-01-01

The etiology of reptilian viral diseases can be attributed to a wide range of viruses occurring across different genera and families. Thirty to forty years ago, studies of viruses in reptiles focused mainly on the zoonotic potential of arboviruses in reptiles and much effort went into surveys and challenge trials of a range of reptiles with eastern and western equine encephalitis as well as Japanese encephalitis viruses. In the past decade, outbreaks of infection with West Nile virus in human populations and in farmed alligators in the USA has seen the research emphasis placed on the issue of reptiles, particularly crocodiles and alligators, being susceptible to, and reservoirs for, this serious zoonotic disease. Although there are many recognised reptilian viruses, the evidence for those being primary pathogens is relatively limited. Transmission studies establishing pathogenicity and cofactors are likewise scarce, possibly due to the relatively low commercial importance of reptiles, difficulties with the availability of animals and permits for statistically sound experiments, difficulties with housing of reptiles in an experimental setting or the inability to propagate some viruses in cell culture to sufficient titres for transmission studies. Viruses as causes of direct loss of threatened species, such as the chelonid fibropapilloma associated herpesvirus and ranaviruses in farmed and wild tortoises and turtles, have re-focused attention back to the characterisation of the viruses as well as diagnosis and pathogenesis in the host itself. 1. Introduction 2. Methods for working with reptilian viruses 3. Reptilian viruses described by virus families 3.1. Herpesviridae 3.2. Iridoviridae 3.2.1 Ranavirus 3.2.2 Erythrocytic virus 3.2.3 Iridovirus 3.3. Poxviridae 3.4. Adenoviridae 3.5. Papillomaviridae 3.6. Parvoviridae 3.7. Reoviridae 3.8. Retroviridae and inclusion body disease of Boid snakes 3.9. Arboviruses 3.9.1. Flaviviridae 3.9.2. Togaviridae 3.10. Caliciviridae 3.11. Picornaviridae 3.12. Paramyxoviridae 4. Summary 5. Acknowledgements 6. Competing interests 7. References PMID:21933449

Active Immunization in the United States: Developments over the Past Decade

PubMed Central

Dennehy, Penelope H.

2001-01-01

The Centers for Disease Control and Prevention has identified immunization as the most important public health advance of the 20th century. The purpose of this article is to review the changes that have taken place in active immunization in the United States over the past decade. Since 1990, new vaccines have become available to prevent five infectious diseases: varicella, rotavirus, hepatitis A, Lyme disease, and Japanese encephalitis virus infection. Improved vaccines have been developed to prevent Haemophilus influenzae type b, pneumococcus, pertussis, rabies, and typhoid infections. Immunization strategies for the prevention of hepatitis B, measles, meningococcal infections, and poliomyelitis have changed as a result of the changing epidemiology of these diseases. Combination vaccines are being developed to facilitate the delivery of multiple antigens, and improved vaccines are under development for cholera, influenza, and meningococcal disease. Major advances in molecular biology have enabled scientists to devise new approaches to the development of vaccines against diseases ranging from respiratory viral to enteric bacterial infections that continue to plague the world's population. PMID:11585789

Change in Dengue and Japanese Encephalitis Seroprevalence Rates in Sri Lanka

PubMed Central

Jeewandara, Chandima; Gomes, Laksiri; Paranavitane, S. A.; Tantirimudalige, Mihiri; Panapitiya, Sumedha Sandaruwan; Jayewardene, Amitha; Fernando, Samitha; Fernando, R. H.; Prathapan, Shamini

2015-01-01

Background Sri Lanka has been affected by epidemics of dengue infections for many decades and the incidence and severity of dengue infections have been rising each year. Therefore, we investigated the age stratified seroprevalence of dengue infections in order to facilitate future dengue vaccine strategies. In addition, since the symptomatic dengue infections have increased during the past few decades, we also investigated the possible association with Japanese Encephalitis Virus (JEV) antibody seropositivity with symptomatic dengue in a community cohort in Sri Lanka. Methods 1689 healthy individuals who were attending a primary health care facility were recruited. Dengue and JEV antibody status was determined in all individuals and JEV vaccination status was recorded. Results 1152/1689 (68.2%) individuals were seropositive for dengue and only 133/1152 (11.5%) of them had been hospitalized to due to dengue. A significant and positive correlation was observed for dengue antibody seropositivity and age in children (Spearmans R = 0.84, p = 0.002) and in adults (Spearmans R = 0.96, p = 0.004). We observed a significant rise in the age stratified seroprevalence rates in children over a period of 12 years. For instance, in year 2003 the annual seroconversion rate was 1.5% per annum, which had risen to 3.79% per annum by 2014. We also found that both adults (p<0.001) and in children (p = 0.03) who were hospitalized due to dengue were more likely to be seropositive for JEV antibodies. However, 244 (91.4%) of adults who were seropositive for JEV had not had the JEV vaccine. Conclusions Dengue seroprevalence rates have risen significantly over the last 12 years in Sri Lanka, possibly due to increased transmission. As individuals who were hospitalized due to dengue were more likely to be seropositive for JEV, the possibility of cross-reactive assays and/or of JEV infection on immunity to the DENV and clinical disease severity should be further investigated. PMID:26696417

The first detection of the tick-borne encephalitis virus (TBEV) RNA in Dermacentor reticulatus ticks collected from the lowland European bison (Bison bonasus bonasus L.).

PubMed

Biernat, Beata; Karbowiak, Grzegorz; Stańczak, Joanna; Masny, Aleksander; Werszko, Joanna

2016-01-01

Tick borne encephalitis virus (TBEV) (Flaviviridae, Flavivirus) is the causative agent of tick-borne encephalitis (TBE), a potentially fatal neurological infection. The disease is endemic in a large region in Eurasia, where is transmitted mainly by hard ticks: Ixodes ricinus and I. persulcatus. It is known that also Dermacentor reticulatus is involved in a circulation of TBEV, but the knowledge of its importance in the TBE epidemiology is still insufficient. The Białowieża Primeval Forest is located in eastern Poland and it is a well-known endemic focus of tick-borne encephalitis. The aim of this study was to identify the prevalence of tick-borne encephalitis virus (TBEV) in Dermacentor reticulatus ticks collected from European bison (Bison bonasus bonasus), an important host of hard ticks in the Białowieża Primeval Forest. In the years 2008-2009, a total of 114 adult D. reticulatus ticks were collected from 7 European bison and examined individually for the presence of TBEV RNA using nested RT-PCR assay. Positive results were noted in 18.42% of ticks. This is the first record of TBEV infection in ticks collected from European bison.

Functional Information Stored in the Conserved Structural RNA Domains of Flavivirus Genomes

PubMed Central

Fernández-Sanlés, Alba; Ríos-Marco, Pablo; Romero-López, Cristina; Berzal-Herranz, Alfredo

2017-01-01

The genus Flavivirus comprises a large number of small, positive-sense single-stranded, RNA viruses able to replicate in the cytoplasm of certain arthropod and/or vertebrate host cells. The genus, which has some 70 member species, includes a number of emerging and re-emerging pathogens responsible for outbreaks of human disease around the world, such as the West Nile, dengue, Zika, yellow fever, Japanese encephalitis, St. Louis encephalitis, and tick-borne encephalitis viruses. Like other RNA viruses, flaviviruses have a compact RNA genome that efficiently stores all the information required for the completion of the infectious cycle. The efficiency of this storage system is attributable to supracoding elements, i.e., discrete, structural units with essential functions. This information storage system overlaps and complements the protein coding sequence and is highly conserved across the genus. It therefore offers interesting potential targets for novel therapeutic strategies. This review summarizes our knowledge of the features of flavivirus genome functional RNA domains. It also provides a brief overview of the main achievements reported in the design of antiviral nucleic acid-based drugs targeting functional genomic RNA elements. PMID:28421048

Parasitic Cowbirds have increased immunity to West Nile and other mosquitoborne encephalitis viruses

USGS Publications Warehouse

Reisen, W.K.; Hahn, D.C.

2006-01-01

The rapid geographic spread of West Nile Virus [WNV, Flaviviridae, Flavivirus] across the United States has stimulated interest in comparative host infection studies of avian species to delineate competent reservoir hosts critical for viral amplification. Striking taxonomic differences in avian susceptibility have been noted, offering the opportunity to strategically select species on the basis of life history traits to examine aspects of pathogen virulence or host immunity. We hypothesized that avian brood parasites would show increased resistance to pathogens compared to related taxa, because they have been exposed in their evolutionary history to a wide array of infectious organisms from their different parenting species. The Brown-headed Cowbird (Molothrus ater) is a generalist brood parasite that parasitizes 200+ North American species. Elevated exposure to other species? parasites may have created an unusual degree of pathogen resistance. We compared the relative susceptibility of adult cowbirds to three closely-related non-parasitic species, Red-winged blackbirds, Tricolored blackbirds and Brewer?s blackbirds, to invading NY99 strain of WNV that is highly virulent for many passeriform birds. Previously we had experimentally infected these species with two North American mosquitoborne encephalitis viruses, western equine encephalomyelitis virus [WEEV, Togaviridae, Alphavirus] and St. Louis encephalitis virus [SLEV, Flaviviridae, Flavivirus]. Our results showed that cowbirds exhibited significantly lower viremia responses against all three viruses as well as after co-infection with both WEEV and WNV than did the three related, non-parasitic species. These data supported our hypothesis and indicated that cowbirds were more resistant to infection to both native and introduced viruses.

Study on the occurrence of tick-borne encephalitis virus RNA in European bison (Bison bonasus) eliminated at Białowieza Primeval Forest (north-eastern Poland) in 2005-2009.

PubMed

Biernat, Beata; Karbowiak, Grzegorz

2014-01-01

Tick-borne encephalitis virus (TBEV) (Flaviviridae, Flavivirus) is an arthropod-borne virus, an etiologic agent of tick-borne encephalitis (TBE), an infection involving the central nervous system. The disease is endemic in a large region in Eurasia where it is transmitted mainly by Ixodes ricinus in Europe and I. persulcatus ticks in Asia. This is the most important tick-transmitted arbovirus of human pathogenicity in Europe. The Białowieza Primeval Forest is a well-known endemic focus of tick-borne encephalitis. The aim of this study was to identify the prevalence of tickborne encephalitis virus (TBEV) in European bison, the important hosts of ticks in the Białowieza Primeval Forest. In the years 2005-2009, 95 blood samples were collected from European bison and examined for the presence of TBEV using nRT-PCR method. No positive results were obtained. For better understanding of TBEV vertebrate reservoir hosts in Poland, further investigations are needed.

Postviral autoimmune encephalitis: manifestations in children and adults.

PubMed

Prüss, Harald

2017-06-01

Autoimmune encephalitis is an increasingly recognized neuropsychiatric condition seen in patients of all ages. Herpes virus infections of the brain can antedate the development of pathogenic autoantibodies against N-methyl-D-aspartate receptors and further neuronal surface proteins, leading to neuronal dysfunction and relapsing symptoms. This review will recapitulate the recent scientific progress, clinical manifestations in children and adults, therapeutic options, and etiological concepts on how autoimmunity develops. Postviral autoimmune encephalitis has been established as disease mechanism after herpes simplex virus encephalitis. Relapsing symptoms in the absence of virus occur in up to 20% of cases. The clinical presentation is relatively stereotyped in children, consisting of choreoathetosis and reduced levels of consciousness. Adults commonly present with psychiatric abnormalities and cognitive changes. Virus-induced antibody generation seems to be a widespread mechanism not confined to Herpesviridae and N-methyl-D-aspartate receptor antibodies SUMMARY: The presence of prolonged, atypical, or relapsing symptoms after virus encephalitis must be actively determined, requiring early follow-up visits of patients, and should always prompt the search for underlying autoantibodies. Relapsing symptoms can markedly improve with immunotherapy, thus treatment, including corticosteroids, plasma separation, immunoglobulins, and rituximab is usually recommended, even if no specific antibody was detected.

Zika fever and congenital Zika syndrome: An unexpected emerging arboviral disease.

PubMed

Chan, Jasper F W; Choi, Garnet K Y; Yip, Cyril C Y; Cheng, Vincent C C; Yuen, Kwok-Yung

2016-05-01

Unlike its mosquito-borne relatives, such as dengue, West Nile, and Japanese encephalitis viruses, which can cause severe human diseases, Zika virus (ZIKV) has emerged from obscurity by its association with a suspected "congenital Zika syndrome", while causing asymptomatic or mild exanthematous febrile infections which are dengue- or rubella-like in infected individuals. Despite having been discovered in Uganda for almost 60 years, <20 human cases were reported before 2007. The massive epidemics in the Pacific islands associated with the ZIKV Asian lineage in 2007 and 2013 were followed by explosive outbreaks in Latin America in 2015. Although increased mosquito breeding associated with the El Niño effect superimposed on global warming is suspected, genetic changes in its RNA virus genome may have led to better adaptation to mosquitoes, other animal reservoirs, and human. We reviewed the epidemiology, clinical manifestation, virology, pathogenesis, laboratory diagnosis, management, and prevention of this emerging infection. Laboratory diagnosis can be confounded by cross-reactivity with other circulating flaviviruses. Besides mosquito bite and transplacental transmission, the risk of other potential routes of transmission by transfusion, transplantation, sexual activity, breastfeeding, respiratory droplet, and animal bite is discussed. Epidemic control requires adequate clearance of mosquito breeding grounds, personal protection against mosquito bite, and hopefully a safe and effective vaccine. Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Cytokine Expression in the Tracheobronchial Lymph Nodes of Pigs Infected with Pseudorabies Virus

USDA-ARS?s Scientific Manuscript database

Pseudorabies virus (PRV) is a neurotropic alphaherpesvirus that produces fatal encephalitis in newborn pigs, respiratory disorders in fattening pigs and reproductive failure in sows. Infection of the respiratory tract by PRV, involves mononuclear cells in draining tracheobronchial lymph nodes (TBLN)...

Mutation analysis of the fusion domain region of St. Louis encephalitis virus envelope protein

DOE Office of Scientific and Technical Information (OSTI.GOV)

Trainor, Nicole B.; Crill, Wayne D.; Roberson, Jill A.

2007-04-10

The immune response to flavivirus infections produces both species-specific and flavivirus cross-reactive antibodies. The presence of cross-reactive antibodies complicates serodiagnosis of flavivirus infections, especially secondary infections caused by a heterologous virus. A successful public health response to the growing global threat posed by flaviviruses necessitates the development of virus-specific diagnostic antigens. The flavivirus envelope (E) glycoprotein is the principle antigen stimulating protective immunity during infection. Using recombinant St. Louis encephalitis virus-like particles (VLPs), we have identified amino acid residues involved in flavivirus cross-reactive epitope determinants. Most significant among the residues studied are three highly conserved amino acids in the fusionmore » peptide: Gly104, Gly106, and Leu107. Substitutions of these residues dramatically influenced VLP secretion and cross-reactive monoclonal antibody reactivity. These results provide critical insight into the antigenic structure of the flaviviral E protein and toward development of species-specific diagnostic antigens that should improve both flavivirus diagnosis and estimates of disease burden.« less

Last 20 aa of the West Nile virus NS1' protein are responsible for its retention in cells and the formation of unique heat-stable dimers.

PubMed

Young, Lucy B; Melian, Ezequiel Balmori; Setoh, Yin Xiang; Young, Paul R; Khromykh, Alexander A

2015-05-01

West Nile virus (WNV), a mosquito-borne flavivirus, is the major cause of arboviral encephalitis in the USA. As with other members of the Japanese encephalitis virus serogroup, WNV produces an additional non-structural protein, NS1', a C-terminal extended product of NS1 generated as the result of a -1 programmed ribosomal frameshift (PRF). We have previously shown that mutations abolishing the PRF, and consequently NS1', resulted in reduced neuroinvasiveness. However, whether this was caused by the PRF event itself or by the lack of a PRF product, NS1', or a combination of both, remains undetermined. Here, we showed that WNV NS1' formed a unique subpopulation of heat- and low-pH-stable dimers. C-terminal truncations and mutational analysis employing an NS1'-expressing plasmid showed that stability of NS1' dimers was linked to the penultimate 10 aa. To examine the role of NS1' heat-stable dimers in virus replication and pathogenicity, a stop codon mutation was introduced into NS1' to create a WNV producing a truncated version of NS1' lacking the last 20 aa, but not affecting the PRF. NS1' protein produced by this mutant virus was secreted more efficiently than WT NS1', indicating that the sequence of the last 20 aa of NS1' was responsible for its cellular retention. Further analysis of this mutant showed growth kinetics in cells and virulence in weanling mice after peripheral infection similar to the WT WNVKUN, suggesting that full-length NS1' was not essential for virus replication in vitro and for virulence in mice. © 2015 The Authors.

Diagnosis and treatment of viral encephalitis

PubMed Central

Chaudhuri, A; Kennedy, P

2002-01-01

Acute encephalitis constitutes a medical emergency. In most cases, the presence of focal neurological signs and focal seizures will distinguish encephalitis from encephalopathy. Acute disseminated encephalomyelitis is a non-infective inflammatory encephalitis that may require to be treated with steroids. Acute infective encephalitis is usually viral. Herpes simplex encephalitis (HSE) is the commonest sporadic acute viral encephalitis in the Western world. Magnetic resonance imaging of brain is the investigation of choice in HSE and the diagnosis may be confirmed by the polymerase chain reaction test for the virus in the cerebrospinal fluid. In this article, we review the diagnosis, investigations, and management of acute encephalitis. With few exceptions (for example, aciclovir for HSE), no specific therapy is available for most forms of viral encephalitis. Mortality and morbidity may be high and long term sequelae are known among survivors. The emergence of unusual forms of zoonotic encephalitis has posed an important public health problem. Vaccination and vector control measures are useful preventive strategies in certain arboviral and zoonotic encephalitis. However, we need better antiviral therapy to meet the challenge of acute viral encephalitis more effectively. PMID:12415078

West Nile seroprevalence study in Bolivian horses, 2011.

PubMed

Mazzei, Maurizio; Savini, Giovanni; Di Gennaro, Annapia; Macchioni, Fabio; Prati, Maria Cristina; Guzmàn, Limberg Rojas; Tolari, Francesco

2013-12-01

West Nile virus (WNV) is a mosquito-borne virus belonging to the family Flaviviridae included in the Japanese encephalitis antigenic complex (JEAC). A seroepidemiological study was carried out in 2011 using 160 horse sera collected from different areas of Bolivia to investigate the presence of WNV antibody. A high proportion (59.4%) of the tested sera were positive to a commercially available WNV competitive enzyme-linked immunosorbent assay (C-ELISA). Sixty-six randomly selected C-ELISA-positive sera were further tested by WNV plaque reduction neutralization test (PRNT), virus neutralization (VN), and immunoglobulin M (IgM)-WNV ELISA to exclude false-positive results due to possible cross-reactions to other members of the JEAC and to investigate if the horses were recently infected. No WNV IgM was detected in these samples, whereas neutralizing antibodies were found in 21 and 18 samples by PRNT and VN, respectively. In conclusion, a high proportion of the Bolivian horses included in this study reacted serologically against viruses of the JEAC. WNV was partially responsible (31.8%) for these reactions, supporting the conclusion that WNV circulated in Bolivia.

Incidence of varicella zoster virus infections of the central nervous system in the elderly: a large tertiary hospital-based series (2007-2014).

PubMed

Arruti, M; Piñeiro, L D; Salicio, Y; Cilla, G; Goenaga, M A; López de Munain, A

2017-06-01

The aim of the study was to describe the clinical and epidemiological characteristics of the central nervous system (CNS) infection by varicella zoster virus (VZV) in patients older than 65 years in a tertiary community hospital. We retrospectively analysed the results of cerebrospinal fluid (CSF) testing in patients older than 65 years between 2007 and 2014 with clinically suspected VZV infection with CNS involvement. Patients whose CSF samples were positive for VZV DNA were included, as were those with negative results who simultaneously presented herpes zoster and CSF or magnetic resonance imaging findings suggestive of CNS infection, and in whom other possible aetiologies had been ruled out. The study included 280 patients. The disease was considered to be caused by a VZV infection in 32 patients (11.4%), of which 23 cases were virologically confirmed (detection of VZV DNA in CSF). The most frequent diagnosis of the patients with VZV CNS infection was encephalitis (83.3%), followed by meningitis (13.3%) and cerebellitis (3.3%). The mean annual incidence of VZV CNS infection was 3.0 cases per 100,000 inhabitants. VZV was the most common cause of encephalitis and viral meningitis, ahead of herpes simplex virus (n = 9). At the time of discharge, 12 (40%) patients showed neurological sequelae. Five patients (20%) died during hospitalization, all with encephalitis. Patients with a fatal outcome had significantly higher median age and longer delay before initiating acyclovir. In conclusion, VZV was the first cause of encephalitis in our elderly population. Despite acyclovir treatment, there was a high rate of case fatality and sequelae at discharge.

A Multi-Agent Alphavirus DNA Vaccine Delivered by Intramuscular Electroporation Elicits Robust and Durable Virus Specific Immune Responses in Mice and Rabbits and Completely Protects Mice against Lethal Venezuelan, Western, and Eastern Equine Encephalitis Virus Aerosol Challenges

DTIC Science & Technology

2016-07-26

protection against aerosol viral challenge in animal studies (13-15). In addition, immune 89 interference has been documented when the VEEV, EEEV, and WEEV...in developing protective DNA vaccines for WEEV and EEEV that 536 provide significantly increased protection against lethal viral aerosol challenge...Arboviral infections in the United States. Infect Dis Clin North Am 5:73-102. 723 3. Bale JF, Jr. 1993. Viral encephalitis. Med Clin North Am 77:25-42. 724

Present and future arboviral threats.

PubMed

Weaver, Scott C; Reisen, William K

2010-02-01

Arthropod-borne viruses (arboviruses) are important causes of human disease nearly worldwide. All arboviruses circulate among wild animals, and many cause disease after spillover transmission to humans and agriculturally important domestic animals that are incidental or dead-end hosts. Viruses such as dengue (DENV) and chikungunya (CHIKV) that have lost the requirement for enzootic amplification now produce extensive epidemics in tropical urban centers. Many arboviruses recently have increased in importance as human and veterinary pathogens using a variety of mechanisms. Beginning in 1999, West Nile virus (WNV) underwent a dramatic geographic expansion into the Americas. High amplification associated with avian virulence coupled with adaptation for replication at higher temperatures in mosquito vectors, has caused the largest epidemic of arboviral encephalitis ever reported in the Americas. Japanese encephalitis virus (JEV), the most frequent arboviral cause of encephalitis worldwide, has spread throughout most of Asia and as far south as Australia from its putative origin in Indonesia and Malaysia. JEV has caused major epidemics as it invaded new areas, often enabled by rice culture and amplification in domesticated swine. Rift Valley fever virus (RVFV), another arbovirus that infects humans after amplification in domesticated animals, undergoes epizootic transmission during wet years following droughts. Warming of the Indian Ocean, linked to the El Niño-Southern Oscillation in the Pacific, leads to heavy rainfall in east Africa inundating surface pools and vertically infected mosquito eggs laid during previous seasons. Like WNV, JEV and RVFV could become epizootic and epidemic in the Americas if introduced unintentionally via commerce or intentionally for nefarious purposes. Climate warming also could facilitate the expansion of the distributions of many arboviruses, as documented for bluetongue viruses (BTV), major pathogens of ruminants. BTV, especially BTV-8, invaded Europe after climate warming and enabled the major midge vector to expand is distribution northward into southern Europe, extending the transmission season and vectorial capacity of local midge species. Perhaps the greatest health risk of arboviral emergence comes from extensive tropical urbanization and the colonization of this expanding habitat by the highly anthropophilic (attracted to humans) mosquito, Aedes aegypti. These factors led to the emergence of permanent endemic cycles of urban DENV and CHIKV, as well as seasonal interhuman transmission of yellow fever virus. The recent invasion into the Americas, Europe and Africa by Aedes albopictus, an important CHIKV and secondary DENV vector, could enhance urban transmission of these viruses in tropical as well as temperate regions. The minimal requirements for sustained endemic arbovirus transmission, adequate human viremia and vector competence of Ae. aegypti and/or Ae. albopictus, may be met by two other viruses with the potential to become major human pathogens: Venezuelan equine encephalitis virus, already an important cause of neurological disease in humans and equids throughout the Americas, and Mayaro virus, a close relative of CHIKV that produces a comparably debilitating arthralgic disease in South America. Further research is needed to understand the potential of these and other arboviruses to emerge in the future, invade new geographic areas, and become important public and veterinary health problems. Copyright 2009 Elsevier B.V. All rights reserved.

Animal models of highly pathogenic RNA viral infections: encephalitis viruses.

PubMed

Holbrook, Michael R; Gowen, Brian B

2008-04-01

The highly pathogenic RNA viruses that cause encephalitis include a significant number of emerging or re-emerging viruses that are also considered potential bioweapons. Many of these viruses, including members of the family Flaviviridae, the genus Alphavirus in the family Togaviridae, and the genus Henipavirus in the family Paramyxoviridae, circulate widely in their endemic areas, where they are transmitted by mosquitoes or ticks. They use a variety of vertebrate hosts, ranging from birds to bats, in their natural life cycle. As was discovered in the United States, the introduction of a mosquito-borne encephalitis virus such as West Nile virus can cause significant health and societal concerns. There are no effective therapeutics for treating diseases caused by any of these viruses and there is limited, if any, vaccine availability for most. In this review we provide a brief summary of the current status of animal models used to study highly pathogenic encephalitic RNA viruses for the development of antiviral therapeutics and vaccines.

Exploiting mosquito sugar feeding to detect mosquito-borne pathogens

PubMed Central

Hall-Mendelin, Sonja; Ritchie, Scott A.; Johansen, Cheryl A.; Zborowski, Paul; Cortis, Giles; Dandridge, Scott; Hall, Roy A.; van den Hurk, Andrew F.

2010-01-01

Arthropod-borne viruses (arboviruses) represent a global public health problem, with dengue viruses causing millions of infections annually, while emerging arboviruses, such as West Nile, Japanese encephalitis, and chikungunya viruses have dramatically expanded their geographical ranges. Surveillance of arboviruses provides vital data regarding their prevalence and distribution that may be utilized for biosecurity measures and the implementation of disease control strategies. However, current surveillance methods that involve detection of virus in mosquito populations or sero-conversion in vertebrate hosts are laborious, expensive, and logistically problematic. We report a unique arbovirus surveillance system to detect arboviruses that exploits the process whereby mosquitoes expectorate virus in their saliva during sugar feeding. In this system, infected mosquitoes captured by CO2-baited updraft box traps are allowed to feed on honey-soaked nucleic acid preservation cards within the trap. The cards are then analyzed for expectorated virus using real-time reverse transcription-PCR. In field trials, this system detected the presence of Ross River and Barmah Forest viruses in multiple traps deployed at two locations in Australia. Viral RNA was preserved for at least seven days on the cards, allowing for long-term placement of traps and continuous collection of data documenting virus presence in mosquito populations. Furthermore no mosquito handling or processing was required and cards were conveniently shipped to the laboratory overnight. The simplicity and efficacy of this approach has the potential to transform current approaches to vector-borne disease surveillance by streamlining the monitoring of pathogens in vector populations. PMID:20534559

Effects of virus dose and extrinsic incubation temperature on vector competence of Culex nigripalpus (Diptera: Culicidae) for St. Louis encephalitis virus.

PubMed

Richards, Stephanie L; Anderson, Sheri L; Lord, Cynthia C; Tabachnick, Walter J

2012-11-01

Culex nigripalpus Theobald is a primary vector of St. Louis encephalitis virus in the southeastern United States. Cx. nigripalpus females were fed blood containing a low (4.0 +/- 0.01 log10 plaque-forming unit equivalents (PFUeq) /ml) or high (4.7 +/- 0.1 log10 PFUeq/ml) St. Louis encephalitis virus dose and maintained at extrinsic incubation temperatures (EIT) of 25 or 28 degrees C for 12 d. Vector competence was measured via quantitative real-time reverse transcriptase polymerase chain reaction to estimate PFUeq using rates of infection, dissemination, and transmission. There were no differences in infection rates between the two EITs at either dose. The low dose had higher infection rates at both EITs. Dissemination rates were significantly higher at 28 degrees C compared with 25 degrees C at both doses. Virus transmission was observed (<7%) only at 28 degrees C for both doses. The virus titer in body tissues was greater at 28 degrees C compared with 25 degrees C at both doses. The difference between the EITs was greater at the low dose, resulting in a higher titer for the low dose than the high dose at 28 degrees C. Virus titers in leg tissues were greater in mosquitoes fed the high versus low dose, but were not influenced by EIT. Further investigations using a variety of environmental and biological factors would be useful in exploring the complexity of vector competence.

Effects of Virus Dose and Extrinsic Incubation Temperature on Vector Competence of Culex nigripalpus (Diptera: Culicidae) for St. Louis Encephalitis Virus

PubMed Central

RICHARDS, STEPHANIE L.; ANDERSON, SHERI L.; LORD, CYNTHIA C.; TABACHNICK, WALTER J.

2013-01-01

Culex nigripalpus Theobald is a primary vector of St. Louis encephalitis virus in the southeastern United States. Cx. nigripalpus females were fed blood containing a low (4.0 ± 0.01 log10 plaque-forming unit equivalents (PFUeq)/ml) or high (4.7 ± 0.1 log10 PFUeq/ml) St. Louis encephalitis virus dose and maintained at extrinsic incubation temperatures (EIT) of 25 or 28°C for 12 d. Vector competence was measured via quantitative real-time reverse transcriptase polymerase chain reaction to estimate PFUeq using rates of infection, dissemination, and transmission. There were no differences in infection rates between the two EITs at either dose. The low dose had higher infection rates at both EITs. Dissemination rates were significantly higher at 28°C compared with 25°C at both doses. Virus transmission was observed (<7%) only at 28°C for both doses. The virus titer in body tissues was greater at 28°C compared with 25°C at both doses. The difference between the EITs was greater at the low dose, resulting in a higher titer for the low dose than the high dose at 28°C. Virus titers in leg tissues were greater in mosquitoes fed the high versus low dose, but were not influenced by EIT. Further investigations using a variety of environmental and biological factors would be useful in exploring the complexity of vector competence. PMID:23270182

Experimental infection of goats with tick-borne encephalitis virus and the possibilities to prevent virus transmission by raw goat milk.

PubMed

Balogh, Zsuzsanna; Egyed, László; Ferenczi, Emőke; Bán, Enikő; Szomor, Katalin N; Takács, Mária; Berencsi, György

2012-01-01

The aim of this work was to study the tick-borne encephalitis virus (TBEV) infection of goats and the possibilities to prevent human milk-borne infections either by immunizing animals or the heat treatment of milk. An experiment was conducted with 20 milking goats. Ten goats (half of them immunized) were challenged with live TBEV and 10 were left uninfected. Clinical signs and body temperatures of the animals were recorded and milk samples were collected daily. The presence of viral RNA and infectious virions in milk were detected by RT-PCR and intracerebral inoculation of suckling mice, respectively. Milk samples containing infectious virions were subjected to various heat treatment conditions and retested afterwards to assess the effect on infectivity. The infected goats did not show any clinical signs or fever compared to uninfected ones. Infectious virions were detected for 8-19 days from the milk samples (genome for 3-18 days by PCR) of infected goats. Immunized goats did not shed the virus. After heat treatment of the milk, the inoculated mice survived. Goats shed the virus with their milk without showing any symptoms. Human milk-borne infections can be avoided both by immunizing goats and boiling/pasteurizing infected milk. Copyright © 2011 S. Karger AG, Basel.

[Role of Toscana virus in meningo-encephalitis in Tunisia].

PubMed

Bahri, O; Fazaa, O; Ben Alaya-Bouafif, N; Bouloy, M; Triki, H; Bouattour, A

2011-12-01

To detect the presence of Toscana virus (TOSV) circulation in Tunisia and to study its role in viral meningo-encephalitis. A total of 315 (167 sera and 178 cerobrospinal fluid [CSF]) samples was investigated. These samples are colleted from Tunisian patients with neurological diseases during the period between January 2003 and December 2009. All samples were tested negative for enterovirus, Herpes Simplex virus and West Nile virus. Detection for IgM and IgG specific to TOSV was done by ELISA tests. Specific IgM for TOSV were detected in 10 % of patients with neurological diseases (31 cases). These recent infections were distributed throughout the study period and predominated during summer and automn. Patients were originated, in the majority from the coastal region. IgG were isolated in 22 cases (7 %) corresponding to previous infection. This is the first report of TOSV circulating in Tunisia and its frequent implication in neurological diseases. These results incited to include TOSV as one of the viral etiologies to target in the diagnosis of viral meningitis and encephalitis in the country. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Potential role of deer tick virus in Powassan encephalitis cases in Lyme disease-endemic areas of New York, U.S.A.

PubMed

El Khoury, Marc Y; Camargo, Jose F; White, Jennifer L; Backenson, Bryon P; Dupuis, Alan P; Escuyer, Kay L; Kramer, Laura; St George, Kirsten; Chatterjee, Debarati; Prusinski, Melissa; Wormser, Gary P; Wong, Susan J

2013-12-01

Powassan virus, a member of the tick-borne encephalitis group of flaviviruses, encompasses 2 lineages with separate enzootic cycles. The prototype lineage of Powassan virus (POWV) is principally maintained between Ixodes cookei ticks and the groundhog (Marmota momax) or striped skunk (Mephitis mephitis), whereas the deer tick virus (DTV) lineage is believed to be maintained between Ixodes scapularis ticks and the white-footed mouse (Peromyscus leucopus). We report 14 cases of Powassan encephalitis from New York during 2004-2012. Ten (72%) of the patients were residents of the Lower Hudson Valley, a Lyme disease-endemic area in which I. scapularis ticks account for most human tick bites. This finding suggests that many of these cases were caused by DTV rather than POWV. In 2 patients, DTV infection was confirmed by genetic sequencing. As molecular testing becomes increasingly available, more cases of Powassan encephalitis may be determined to be attributable to the DTV lineage.

Potential Role of Deer Tick Virus in Powassan Encephalitis Cases in Lyme Disease–endemic Areas of New York, USA

PubMed Central

Camargo, Jose F.; White, Jennifer L.; Backenson, Bryon P.; Dupuis, Alan P.; Escuyer, Kay L.; Kramer, Laura; St. George, Kirsten; Chatterjee, Debarati; Prusinski, Melissa; Wormser, Gary P.; Wong, Susan J.

2013-01-01

Powassan virus, a member of the tick-borne encephalitis group of flaviviruses, encompasses 2 lineages with separate enzootic cycles. The prototype lineage of Powassan virus (POWV) is principally maintained between Ixodes cookei ticks and the groundhog (Marmota momax) or striped skunk (Mephitis mephitis), whereas the deer tick virus (DTV) lineage is believed to be maintained between Ixodes scapularis ticks and the white-footed mouse (Peromyscus leucopus). We report 14 cases of Powassan encephalitis from New York during 2004–2012. Ten (72%) of the patients were residents of the Lower Hudson Valley, a Lyme disease–endemic area in which I. scapularis ticks account for most human tick bites. This finding suggests that many of these cases were caused by DTV rather than POWV. In 2 patients, DTV infection was confirmed by genetic sequencing. As molecular testing becomes increasingly available, more cases of Powassan encephalitis may be determined to be attributable to the DTV lineage. PMID:24274334

A MicroRNA Screen Identifies the Wnt Signaling Pathway as a Regulator of the Interferon Response during Flavivirus Infection

PubMed Central

Smith, Jessica L.; Jeng, Sophia; McWeeney, Shannon K.

2017-01-01

ABSTRACT The impact of mosquito-borne flavivirus infections worldwide is significant, and many critical aspects of these viruses' biology, including virus-host interactions, host cell requirements for replication, and how virus-host interactions impact pathology, remain to be fully understood. The recent reemergence and spread of flaviviruses, including dengue virus (DENV), West Nile virus (WNV), and Zika virus (ZIKV), highlight the importance of performing basic research on this important group of pathogens. MicroRNAs (miRNAs) are small, noncoding RNAs that modulate gene expression posttranscriptionally and have been demonstrated to regulate a broad range of cellular processes. Our research is focused on identifying pro- and antiflaviviral miRNAs as a means of characterizing cellular pathways that support or limit viral replication. We have screened a library of known human miRNA mimics for their effect on the replication of three flaviviruses, DENV, WNV, and Japanese encephalitis virus (JEV), using a high-content immunofluorescence screen. Several families of miRNAs were identified as inhibiting multiple flaviviruses, including the miRNA miR-34, miR-15, and miR-517 families. Members of the miR-34 family, which have been extensively characterized for their ability to repress Wnt/β-catenin signaling, demonstrated strong antiflaviviral effects, and this inhibitory activity extended to other viruses, including ZIKV, alphaviruses, and herpesviruses. Previous research suggested a possible link between the Wnt and type I interferon (IFN) signaling pathways. Therefore, we investigated the role of type I IFN induction in the antiviral effects of the miR-34 family and confirmed that these miRNAs potentiate interferon regulatory factor 3 (IRF3) phosphorylation and translocation to the nucleus, the induction of IFN-responsive genes, and the release of type I IFN from transfected cells. We further demonstrate that the intersection between the Wnt and IFN signaling pathways occurs at the point of glycogen synthase kinase 3β (GSK3β)–TANK-binding kinase 1 (TBK1) binding, inducing TBK1 to phosphorylate IRF3 and initiate downstream IFN signaling. In this way, we have identified a novel cellular signaling network with a critical role in regulating the replication of multiple virus families. These findings highlight the opportunities for using miRNAs as tools to discover and characterize unique cellular factors involved in supporting or limiting virus replication, opening up new avenues for antiviral research. IMPORTANCE MicroRNAs are a class of small regulatory RNAs that modulate cellular processes through the posttranscriptional repression of multiple transcripts. We hypothesized that individual miRNAs may be capable of inhibiting viral replication through their effects on host proteins or pathways. To test this, we performed a high-content screen for miRNAs that inhibit the replication of three medically relevant members of the flavivirus family: West Nile virus, Japanese encephalitis virus, and dengue virus 2. The results of this screen identify multiple miRNAs that inhibit one or more of these viruses. Extensive follow-up on members of the miR-34 family of miRNAs, which are active against all three viruses as well as the closely related Zika virus, demonstrated that miR-34 functions through increasing the infected cell's ability to respond to infection through the interferon-based innate immune pathway. Our results not only add to the knowledge of how viruses interact with cellular pathways but also provide a basis for more extensive data mining by providing a comprehensive list of miRNAs capable of inhibiting flavivirus replication. Finally, the miRNAs themselves or cellular pathways identified as modulating virus infection may prove to be novel candidates for the development of therapeutic interventions. PMID:28148804

A MicroRNA Screen Identifies the Wnt Signaling Pathway as a Regulator of the Interferon Response during Flavivirus Infection.

PubMed

Smith, Jessica L; Jeng, Sophia; McWeeney, Shannon K; Hirsch, Alec J

2017-04-15

The impact of mosquito-borne flavivirus infections worldwide is significant, and many critical aspects of these viruses' biology, including virus-host interactions, host cell requirements for replication, and how virus-host interactions impact pathology, remain to be fully understood. The recent reemergence and spread of flaviviruses, including dengue virus (DENV), West Nile virus (WNV), and Zika virus (ZIKV), highlight the importance of performing basic research on this important group of pathogens. MicroRNAs (miRNAs) are small, noncoding RNAs that modulate gene expression posttranscriptionally and have been demonstrated to regulate a broad range of cellular processes. Our research is focused on identifying pro- and antiflaviviral miRNAs as a means of characterizing cellular pathways that support or limit viral replication. We have screened a library of known human miRNA mimics for their effect on the replication of three flaviviruses, DENV, WNV, and Japanese encephalitis virus (JEV), using a high-content immunofluorescence screen. Several families of miRNAs were identified as inhibiting multiple flaviviruses, including the miRNA miR-34, miR-15, and miR-517 families. Members of the miR-34 family, which have been extensively characterized for their ability to repress Wnt/β-catenin signaling, demonstrated strong antiflaviviral effects, and this inhibitory activity extended to other viruses, including ZIKV, alphaviruses, and herpesviruses. Previous research suggested a possible link between the Wnt and type I interferon (IFN) signaling pathways. Therefore, we investigated the role of type I IFN induction in the antiviral effects of the miR-34 family and confirmed that these miRNAs potentiate interferon regulatory factor 3 (IRF3) phosphorylation and translocation to the nucleus, the induction of IFN-responsive genes, and the release of type I IFN from transfected cells. We further demonstrate that the intersection between the Wnt and IFN signaling pathways occurs at the point of glycogen synthase kinase 3β (GSK3β)-TANK-binding kinase 1 (TBK1) binding, inducing TBK1 to phosphorylate IRF3 and initiate downstream IFN signaling. In this way, we have identified a novel cellular signaling network with a critical role in regulating the replication of multiple virus families. These findings highlight the opportunities for using miRNAs as tools to discover and characterize unique cellular factors involved in supporting or limiting virus replication, opening up new avenues for antiviral research. IMPORTANCE MicroRNAs are a class of small regulatory RNAs that modulate cellular processes through the posttranscriptional repression of multiple transcripts. We hypothesized that individual miRNAs may be capable of inhibiting viral replication through their effects on host proteins or pathways. To test this, we performed a high-content screen for miRNAs that inhibit the replication of three medically relevant members of the flavivirus family: West Nile virus, Japanese encephalitis virus, and dengue virus 2. The results of this screen identify multiple miRNAs that inhibit one or more of these viruses. Extensive follow-up on members of the miR-34 family of miRNAs, which are active against all three viruses as well as the closely related Zika virus, demonstrated that miR-34 functions through increasing the infected cell's ability to respond to infection through the interferon-based innate immune pathway. Our results not only add to the knowledge of how viruses interact with cellular pathways but also provide a basis for more extensive data mining by providing a comprehensive list of miRNAs capable of inhibiting flavivirus replication. Finally, the miRNAs themselves or cellular pathways identified as modulating virus infection may prove to be novel candidates for the development of therapeutic interventions. Copyright © 2017 American Society for Microbiology.

Species-specific disruption of STING-dependent antiviral cellular defenses by the Zika virus NS2B3 protease.

PubMed

Ding, Qiang; Gaska, Jenna M; Douam, Florian; Wei, Lei; Kim, David; Balev, Metodi; Heller, Brigitte; Ploss, Alexander

2018-06-18

The limited host tropism of numerous viruses causing disease in humans remains incompletely understood. One example is Zika virus (ZIKV), an RNA virus that has reemerged in recent years. Here, we demonstrate that ZIKV efficiently infects fibroblasts from humans, great apes, New and Old World monkeys, but not rodents. ZIKV infection in human-but not murine-cells impairs responses to agonists of the cGMP-AMP synthase/stimulator of IFN genes (cGAS/STING) signaling pathway, suggesting that viral mechanisms to evade antiviral defenses are less effective in rodent cells. Indeed, human, but not mouse, STING is subject to cleavage by proteases encoded by ZIKV, dengue virus, West Nile virus, and Japanese encephalitis virus, but not that of yellow fever virus. The protease cleavage site, located between positions 78/79 of human STING, is only partially conserved in nonhuman primates and rodents, rendering these orthologs resistant to degradation. Genetic disruption of STING increases the susceptibility of mouse-but not human-cells to ZIKV. Accordingly, expression of only mouse, not human, STING in murine STING knockout cells rescues the ZIKV suppression phenotype. STING-deficient mice, however, did not exhibit increased susceptibility, suggesting that other redundant antiviral pathways control ZIKV infection in vivo. Collectively, our data demonstrate that numerous RNA viruses evade cGAS/STING-dependent signaling and affirm the importance of this pathway in shaping the host range of ZIKV. Furthermore, our results explain-at least in part-the decreased permissivity of rodent cells to ZIKV, which could aid in the development of mice model with inheritable susceptibility to ZIKV and other flaviviruses.

Diagnosis and management of acute encephalitis.

PubMed

Halperin, J J

2017-01-01

Encephalitis is typically viral (approximately half of diagnosed cases) or autoimmune (about a quarter) with the remainder remaining undiagnosable at this time. All require general supportive care but only a minority requires intensive care admission - in these intubation, to protect the airway or to treat status epilepticus with anesthetic drugs, may be needed. In some dysautonomia with wide blood pressure fluctuations is the principal concern. Remarkably, in addition to supportive care, specific treatment options are available for the majority - immune-modulating therapy for those with autoimmune disorders, antiviral therapy for herpes simplex 1 and 2, and varicella-zoster encephalitis. Flavivirus infections (West Nile, Japanese encephalitis, tick-borne encephalitis) remain the most common other identified cause of encephalitis but no specific intervention is available. Overall long-term outcomes are favorable in the majority of patients with encephalitis, a proportion that hopefully will improve with further advances in diagnostic technology and therapeutic interventions. © 2017 Elsevier B.V. All rights reserved.

Electron microscopic diagnosis of human flavivirus encephalitis: use of confocal microscopy as an aid.

PubMed

Chu, C T; Howell, D N; Morgenlander, J C; Hulette, C M; McLendon, R E; Miller, S E

1999-10-01

The distinction between intracranial viral infections and inflammatory conditions requiring immunosuppression is important. Although specific laboratory reagents are readily available for some viruses, diagnosis of arbovirus infection is more difficult. Transmission electron microscopy (TEM) theoretically allows identification of viral particles independent of reagent availability, but it has limited sensitivity. We report two cases of human flavivirus encephalitis diagnosed by TEM. Laser scanning confocal microscopy (LSCM) was used in one case to survey unembedded tissue slices for focal abnormalities, from which fragments smaller than 1 mm2 were excised for epoxy embedding. This facilitated TEM identification of intracytoplasmic, budding, 35-40 nm spherical virus particles, confirmed by serology as St. Louis encephalitis. In contrast to mosquitoes and newborn mice, in which high viral loads are associated with minimal tissue responses, these biopsies showed florid angiodestructive inflammation and microgliosis, with rare virions in necrotic perivascular cells and astrocytes. To our knowledge, this represents the first ultrastructural study of St. Louis encephalitis in humans, indicating the potential value of LSCM-aided TEM.

Genomic changes in an attenuated genotype I Japanese encephalitis virus and comparison with virulent parental strain.

PubMed

Zhou, Yuyong; Wu, Rui; Feng, Yao; Zhao, Qin; Wen, Xintian; Huang, Xiaobo; Wen, Yiping; Yan, Qigui; Huang, Yong; Ma, Xiaoping; Han, Xinfeng; Cao, Sanjie

2018-06-01

Genotype I Japanese encephalitis virus (JEV) strain SCYA201201 was previously isolated from brain tissues of aborted piglets. In this study, we obtained an attenuated SCYA201201-0901 strain by serial passage of strain SCYA201201-1 in Syrian baby hamster kidney cells, combined with multiple plaque purifications and selection for virulence in mice. We investigated the genetic changes associated with attenuation by comparing the entire genomes of SCYA201201-0901 and SCYA201201-1. Sequence comparisons identified 14 common amino acid substitutions in the coding region, with two nucleotide point mutations in the 5'-untranslated region (UTR) and another three in the 3'-UTR, which differed between the attenuated and virulent strains. In addition, a total of 13 silent nucleotide mutations were found after attenuation. These substitutions, alone or in combination, may be responsible for the attenuated phenotype of the SCYA201201-0901 strain in mice. This information will contribute to our understanding of attenuation and of the molecular basis of virulence in genotype I strains such as SCYA201201-0901, as well as aiding the development of safer JEV vaccines.

Japanese encephalitis vaccines: Immunogenicity, protective efficacy, effectiveness, and impact on the burden of disease

PubMed Central

Gore, Milind M.

2017-01-01

ABSTRACT Japanese encephalitis (JE) is a serious public health concern in most of Asia. The disease is caused by JE virus (JEV), a flavivirus transmitted by Culex mosquitoes. Several vaccines have been developed to control JE in endemic areas as well as to protect travelers and military personnel who visit or are commissioned from non-endemic to endemic areas. The vaccines include inactivated vaccines produced in mouse brain or cell cultures, live attenuated vaccines, and a chimeric vaccine based on the live attenuated yellow fever virus 17D vaccine strain. All the marketed vaccines belong to the JEV genotype III, but have been shown to be efficacious against other genotypes and strains, with varying degrees of cross-neutralization, albeit at levels deemed to be protective. The protective responses have been shown to last three or more years, depending on the type of vaccine and the number of doses. This review presents a brief account of the different JE vaccines, their immunogenicity and protective ability, and the impact of JE vaccines in reducing the burden of disease in endemic countries. PMID:28301270

Molecular epidemiology of Japanese encephalitis in northern Vietnam, 1964-2011: genotype replacement.

PubMed

Do, Loan Phuong; Bui, Trang Minh; Hasebe, Futoshi; Morita, Kouichi; Phan, Nga Thi

2015-04-01

Japanese encephalitis virus (JEV) is an arthropod-borne virus causing serious public health issues in Asia. JEV consists of five genotypes and recent studies have shown the emergence of JEV genotype I (GI) and its replacement of genotype III (GIII). Using an archival JEV collection, we investigated the molecular evolution of JEV in Vietnam over the last 48 years (1964-2012) in humans, mosquitoes, and pigs, within the global context. The nine JEV isolates from humans, pigs, and mosquitoes sequenced in this study and 29 sequences available in GenBank were used to analyze the envelope (E) protein of the Vietnamese JEVs. A collection of 225 cerebrospinal fluid specimens from patients with suspected Japanese encephalitis (JE) was also tested and genotyped with real-time RT-PCR. The 38 E genes identified with sequencing and nine Vietnamese JEV strains genotyped with real-time RT-PCR, belonging to two lineages, evolved in accordance with those in the rest of the world. The first GIII strain was detected in humans in Vietnam in 1964, and in mosquitoes in 1979, whereas GI strains were first detected in humans and mosquitoes in 1990 and 1994, respectively. After 2004, GI was the only genotype detected in Vietnam, demonstrating that the GIIII strains had been displaced by GI strains. Five haplotypes were identified in the Vietnamese JEVs, with SKSS predominant. The S123N and S123R substitutions in the E protein were already present in the Vietnamese JEVs. This study describes the long evolutionary history of JEV in Vietnam over 34 years, which correlates well with the global evolution of JEV. The Vietnamese GIII strains have been replaced by GI strains in mosquitoes, pigs, and humans. The predominant haplotypes of the Vietnamese strains support this genotype displacement in Vietnam. Further surveillance is required to confirm the disappearance of the GIII strains in nature and the emergence of new pathogens causing encephalitis in Vietnam, after the long-term use of JEV vaccines in that country.

Structure of the thermally stable Zika virus.

PubMed

Kostyuchenko, Victor A; Lim, Elisa X Y; Zhang, Shuijun; Fibriansah, Guntur; Ng, Thiam-Seng; Ooi, Justin S G; Shi, Jian; Lok, Shee-Mei

2016-05-19

Zika virus (ZIKV), formerly a neglected pathogen, has recently been associated with microcephaly in fetuses, and with Guillian-Barré syndrome in adults. Here we present the 3.7 Å resolution cryo-electron microscopy structure of ZIKV, and show that the overall architecture of the virus is similar to that of other flaviviruses. Sequence and structural comparisons of the ZIKV envelope (E) protein with other flaviviruses show that parts of the E protein closely resemble the neurovirulent West Nile and Japanese encephalitis viruses, while others are similar to dengue virus (DENV). However, the contribution of the E protein to flavivirus pathobiology is currently not understood. The virus particle was observed to be structurally stable even when incubated at 40 °C, in sharp contrast to the less thermally stable DENV. This is also reflected in the infectivity of ZIKV compared to DENV serotypes 2 and 4 (DENV2 and DENV4) at different temperatures. The cryo-electron microscopy structure shows a virus with a more compact surface. This structural stability of the virus may help it to survive in the harsh conditions of semen, saliva and urine. Antibodies or drugs that destabilize the structure may help to reduce the disease outcome or limit the spread of the virus.

Cycluridine: A novel antiviral effective against flaviviruses

PubMed Central

Galabov, Angel S; Mukova, Lucia; Abashev, Yuriy P; Wassilewa, Lilia; Tzvetkov, Petko; Minkov, Vassil; Barinskiy, Igor F; Rice, Charles M; Ouzounov, Sergey; Sidzhakova, Dorotea

2017-01-01

This review describes the contemporary state of research for antivirals effective against flaviviruses, especially focusing on inhibitors of the pestivirus causative agent of bovine viral diarrhoea virus. We highlight cycluridine, an originally synthesized Mannich’s base [a tetrahydro-2(1H)-pyrimidinones derivative], as a highly effective antiviral possessing a strong inhibitory effect on bovine viral diarrhoea virus replication. Cycluridine was active against replication of a wide variety of bovine viral diarrhoea virus strains in cell cultures. The drug-sensitive period in the bovine viral diarrhoea virus replication cycle included the latent period and the exponential phase; a 90-min delay in the peak of viral RNA synthesis was observed. Cycluridine administered orally manifested a pronounced protective effect in calves with natural mucosal disease/viral diarrhoea and calves experimentally infected with bovine viral diarrhoea virus. Its magnitude of activity and selectivity places cycluridine in the lead among all known substances with anti- bovine viral diarrhoea virus activity. Additionally, cycluridine applied subcutaneously showed anti-tick-born encephalitis virus activity, manifesting a marked protective effect in mice infected with tick-born encephalitis virus. Cycluridine could be a prospective antiviral in veterinary and medical practice for the treatment of bovine viral diarrhoea virus and other flavivirus infections. PMID:28768435

Management of adult infectious encephalitis in metropolitan France.

PubMed

Goulenok, T; Buzelé, R; Duval, X; Bruneel, F; Stahl, J P; Fantin, B

2017-05-01

Infectious encephalitis is a severe disease leading to a high mortality and morbidity. The most frequent causes include Herpes simplex virus, Varicella Zoster virus, Listeria monocytogenes, and Mycobacterium tuberculosis. Urgent treatment is required (anti-infective therapy and nonspecific supportive care). The aim of this study was to define treatment strategy, empirical and after microbiological documentation at 48hours, through a systematic literature review. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Utilisation of ISA Reverse Genetics and Large-Scale Random Codon Re-Encoding to Produce Attenuated Strains of Tick-Borne Encephalitis Virus within Days.

PubMed

de Fabritus, Lauriane; Nougairède, Antoine; Aubry, Fabien; Gould, Ernest A; de Lamballerie, Xavier

2016-01-01

Large-scale codon re-encoding is a new method of attenuating RNA viruses. However, the use of infectious clones to generate attenuated viruses has inherent technical problems. We previously developed a bacterium-free reverse genetics protocol, designated ISA, and now combined it with large-scale random codon-re-encoding method to produce attenuated tick-borne encephalitis virus (TBEV), a pathogenic flavivirus which causes febrile illness and encephalitis in humans. We produced wild-type (WT) and two re-encoded TBEVs, containing 273 or 273+284 synonymous mutations in the NS5 and NS5+NS3 coding regions respectively. Both re-encoded viruses were attenuated when compared with WT virus using a laboratory mouse model and the relative level of attenuation increased with the degree of re-encoding. Moreover, all infected animals produced neutralizing antibodies. This novel, rapid and efficient approach to engineering attenuated viruses could potentially expedite the development of safe and effective new-generation live attenuated vaccines.

Tick-borne encephalitis virus infects human brain microvascular endothelial cells without compromising blood-brain barrier integrity.

PubMed

Palus, Martin; Vancova, Marie; Sirmarova, Jana; Elsterova, Jana; Perner, Jan; Ruzek, Daniel

2017-07-01

Alteration of the blood-brain barrier (BBB) is a hallmark of tick-borne encephalitis (TBE), a life-threating human viral neuroinfection. However, the mechanism of BBB breakdown during TBE, as well as TBE virus (TBEV) entry into the brain is unclear. Here, primary human microvascular endothelial cells (HBMECs) were infected with TBEV to study interactions with the BBB. Although the number of infected cells was relatively low in culture (<5%), the infection was persistent with high TBEV yields (>10 6 pfu/ml). Infection did not induce any significant changes in the expression of key tight junction proteins or upregulate the expression of cell adhesion molecules, and did not alter the highly organized intercellular junctions between HBMECs. In an in vitro BBB model, the virus crossed the BBB via a transcellular pathway without compromising the integrity of the cell monolayer. The results indicate that HBMECs may support TBEV entry into the brain without altering BBB integrity. Copyright © 2017 Elsevier Inc. All rights reserved.

Properties of the tick-borne encephalitis virus population during persistent infection of ixodid ticks and tick cell lines.

PubMed

Belova, Oxana A; Litov, Alexander G; Kholodilov, Ivan S; Kozlovskaya, Liubov I; Bell-Sakyi, Lesley; Romanova, Lidiya Iu; Karganova, Galina G

2017-10-01

Tick-borne encephalitis virus (TBEV) is the causative agent of tick-borne encephalitis (TBE), a vector-borne zoonotic neuroinfection. For successful circulation in natural foci the virus has to survive in the vector for a long period of time. Information about the effect of long-term infection of ticks on properties of the viral population is of great importance. In recent years, changes in the eco-epidemiology of TBEV due to changes in distribution of ixodid ticks have been observed. These changes in TBEV-endemic areas could result in a shift of the main tick vector species, which in turn may lead to changes in properties of the virus. In the present study we evaluated the selective pressure on the TBEV population during persistent infection of various species of ticks and tick cell lines. TBEV effectively replicated and formed persistent infection in ticks and tick cell lines of the vector species (Ixodes spp.), potential vectors (Dermacentor spp.) and non-vector ticks (Hyalomma spp.). During TBEV persistence in Ixodes and Dermacentor ticks, properties of the viral population remained virtually unchanged. In contrast, persistent TBEV infection of tick cell lines from both vector and non-vector ticks favoured selection of viral variants with low neuroinvasiveness for laboratory mice and substitutions in the E protein that increased local positive charge of the virion. Thus, selective pressure on viral population may differ in ticks and tick cell lines during persistent infection. Nevertheless, virus variants with properties of the original strain adapted to mouse CNS were not eliminated from the viral population during long-term persistence of TBEV in ticks and tick cell lines. Copyright © 2017 Elsevier GmbH. All rights reserved.

Herpes simplex virus serotype and entry receptor availability alter CNS disease in a mouse model of neonatal HSV.

PubMed

Kopp, Sarah J; Ranaivo, Hantamalala R; Wilcox, Douglas R; Karaba, Andrew H; Wainwright, Mark S; Muller, William J

2014-12-01

Outcomes of neonates with herpes simplex virus (HSV) encephalitis are worse after infection with HSV-2 when compared with HSV-1. The proteins herpes virus entry mediator (HVEM) and nectin-1 mediate HSV entry into susceptible cells. Prior studies have shown receptor-dependent differences in pathogenesis that depend on route of inoculation and host developmental age. We investigated serotype-related differences in HSV disease and their relationship to entry receptor availability in a mouse model of encephalitis. Mortality was attenuated in 7-d-old, wild-type (WT) mice inoculated with HSV-1(F) when compared with HSV-2(333). No serotype-specific differences were seen after inoculation of adult mice. HSV-1 pathogenesis was also attenuated relative to HSV-2 in newborn but not adult mice lacking HVEM or nectin-1. HSV-2 requires nectin-1 for encephalitis in adult but not newborn mice; in contrast, nectin-1 was important for HSV-1 pathogenesis in both age groups. Early viral replication was independent of age, viral serotype, or mouse genotype, suggesting host responses influence outcomes. In this regard, significantly greater amounts of inflammatory mediators were detected in brain homogenates from WT newborns 2 d after infection compared with adults and receptor-knockout newborns. Dysregulation of inflammatory responses induced by infection may influence the severity of HSV encephalitis.

Aerial applications of ultra-low-volume insecticides to control the vector of Japanese encephalitis in Korea

PubMed Central

Self, L. S.; Ree, H. I.; Lofgren, C. S.; Shim, J. C.; Chow, C. Y.; Shin, H. K.; Kim, K. H.

1973-01-01

As a suitable emergency measure to arrest epidemics of Japanese encephalitis in Korea, the ultra-low-volume method of spraying insecticide to control the mosquito vector Culex tritaeniorhynchus has been tested in 2 successive years over a 16-km 2 area, utilizing a large fixed-wing aircraft. Malathion concentrate applied at 0.36 litres/ha gave insufficient control of the parous (infective) females, and no reduction in total numbers of this species. Fenitrothion concentrate applied at 0.45 litres/ha resulted in a 77-87% reduction in total numbers and an 87-98% reduction in parous females over a 4-day period. PMID:4368385

Lipids and flaviviruses, present and future perspectives for the control of dengue, Zika, and West Nile viruses.

PubMed

Martín-Acebes, Miguel A; Vázquez-Calvo, Ángela; Saiz, Juan-Carlos

2016-10-01

Flaviviruses are emerging arthropod-borne pathogens that cause life-threatening diseases such as yellow fever, dengue, West Nile encephalitis, tick-borne encephalitis, Kyasanur Forest disease, tick-borne encephalitis, or Zika disease. This viral genus groups >50 viral species of small enveloped plus strand RNA virus that are phylogenetically closely related to hepatitis C virus. Importantly, the flavivirus life cycle is intimately associated to host cell lipids. Along this line, flaviviruses rearrange intracellular membranes from the endoplasmic-reticulum of the infected cells to develop adequate platforms for viral replication and particle biogenesis. Moreover, flaviviruses dramatically orchestrate a profound reorganization of the host cell lipid metabolism to create a favorable environment for viral multiplication. Consistently, recent work has shown the importance of specific lipid classes in flavivirus infections. For instances, fatty acid synthesis is linked to viral replication, phosphatidylserine and phosphatidylethanolamine are involved on the entry of flaviviruses, sphingolipids (ceramide and sphingomyelin) play a key role on virus assembly and pathogenesis, and cholesterol is essential for innate immunity evasion in flavivirus-infected cells. Here, we revise the current knowledge on the interactions of the flaviviruses with the cellular lipid metabolism to identify potential targets for future antiviral development aimed to combat these relevant health-threatening pathogens. Copyright © 2016 Elsevier B.V. All rights reserved.

Nipah virus outbreak in Malaysia.

PubMed

Chua, Kaw Bing

2003-04-01

Nipah virus, a novel paramyxovirus, closely related to Hendra virus emerged in northern part of Peninsular Malaysia in 1998. The virus caused an outbreak of severe febrile encephalitis in humans with a high mortality rate, whereas, in pigs, encephalitis and respiratory diseases but with a relatively low mortality rate. The outbreak subsequently spread to various regions of the country and Singapore in the south due to the movement of infected pigs. Nipah virus caused systemic infections in humans, pigs and other mammals. Histopathological and radiological findings were characteristic of the disease. Fruitbats of Pteropid species were identified as the natural reservoir hosts. Evidence suggested that climatic and anthropogenic driven ecological changes coupled with the location of piggeries in orchard and the design of pigsties allowed the spill-over of this novel paramyxovirus from its reservoir host into the domestic pigs and ultimately to humans and other animals.

West Nile Virus Infection in Sheep.

PubMed

Rimoldi, G; Mete, A; Adaska, J M; Anderson, M L; Symmes, K P; Diab, S

2017-01-01

West Nile virus (WNV) infection has been detected in many species of birds and mammals, but scant information is available about the disease in small ruminants. West Nile virus was diagnosed in 6 sheep with neurological signs and encephalitis, in California between 2002 and 2014. All sheep had severe lymphoplasmacytic meningoencephalitis. Lymphoplasmacytic myelitis was also detected in 2 sheep where the spinal cord was examined. Brain tissue was positive for WNV detected by polymerase chain reaction in 6 of 6 sheep and by immunohistochemistry (IHC) in 5 of 6 sheep. Viral antigen was not detected by IHC in extraneural tissues in the 3 sheep examined. West Nile virus RNA was sequenced from 2 of 6 sheep, and each one clusters closely with WNV isolated from mosquito pools from nearby locations at similar times. West Nile virus was the most common cause of viral encephalitis in sheep diagnosed at this laboratory between 2002 and 2014, accounting for 6 of 9 sheep.

Ocular histopathology in Eastern equine encephalitis: A case report.

PubMed

Lad, Eleonora M; Ong, Sally S; Proia, Alan D

2017-04-01

To describe the ophthalmic symptoms and histopathological findings in a human case of Eastern equine encephalitis (EEE). The patient was a septuagenarian male whose presentation and clinical course were thought to be most consistent with viral meningoencephalitis. ELISA suggested recent infection with EEE virus. Microscopic analysis of the brain demonstrated perivascular lymphohistiocytic cuffing which was consistent with viral type encephalitis. Similarly, both eyes manifested a lymphohistiocytic infiltrate in the retina and optic nerve and a reduced number of ganglion cells. To our knowledge, this is the first report of ophthalmological and ocular pathology observations in an EEE patient. Interestingly, the inflammatory findings in the retina are reminiscent of the central nervous system effects of EEE virus. These findings are relevant given the recent epidemic of microcephaly and ophthalmic complications secondary to another arboviral virus, the Zika virus.

Identifying Attenuating Mutations: Tools for a New Vaccine Design against Flaviviruses.

PubMed

Khou, Cécile; Pardigon, Nathalie

2017-01-01

Emerging Flaviviruses pose an increasing threat to global human health. To date, human vaccines against yellow fever virus (YFV), Japanese encephalitis virus (JEV), dengue virus (DV), and tick-borne encephalitis virus (TBEV) exist. However, there is no human vaccine against other Flaviviruses such as Zika virus (ZIKV) and West Nile virus (WNV). In order to restrict their spread and to protect populations against the diseases they induce, vaccines against these emerging viruses must be designed. Obtaining new live attenuated Flavivirus vaccines using molecular biology methods is now possible. Molecular infectious clones of the parental viruses are relatively easy to generate. Key mutations present in live attenuated vaccines or mutations known to have a key role in the Flavivirus life cycle and/or interactions with their hosts can be identified by sequencing, and are then inserted in infectious clones by site-directed mutagenesis. More recently, the use of chimeric viruses and large-scale reencoding and introduction of microRNA target sequences have also been tested. Indeed, a combination of these methods will help in designing new generations of vaccines against emerging and reemerging Flaviviruses. © 2017 S. Karger AG, Basel.

Guiding dengue vaccine development using knowledge gained from the success of the yellow fever vaccine

PubMed Central

Liang, Huabin; Lee, Min; Jin, Xia

2016-01-01

Flaviviruses comprise approximately 70 closely related RNA viruses. These include several mosquito-borne pathogens, such as yellow fever virus (YFV), dengue virus (DENV), and Japanese encephalitis virus (JEV), which can cause significant human diseases and thus are of great medical importance. Vaccines against both YFV and JEV have been used successfully in humans for decades; however, the development of a DENV vaccine has encountered considerable obstacles. Here, we review the protective immune responses elicited by the vaccine against YFV to provide some insights into the development of a protective DENV vaccine. PMID:26435066

Guiding dengue vaccine development using knowledge gained from the success of the yellow fever vaccine.

PubMed

Liang, Huabin; Lee, Min; Jin, Xia

2016-01-01

Flaviviruses comprise approximately 70 closely related RNA viruses. These include several mosquito-borne pathogens, such as yellow fever virus (YFV), dengue virus (DENV), and Japanese encephalitis virus (JEV), which can cause significant human diseases and thus are of great medical importance. Vaccines against both YFV and JEV have been used successfully in humans for decades; however, the development of a DENV vaccine has encountered considerable obstacles. Here, we review the protective immune responses elicited by the vaccine against YFV to provide some insights into the development of a protective DENV vaccine.

Mosquito Bites

MedlinePlus

... humans. Other mosquito-borne infections include yellow fever, malaria and some types of brain infection (encephalitis). Symptoms ... carry certain diseases, such as West Nile virus, malaria, yellow fever and dengue fever. The mosquito obtains ...

Acute West Nile Virus Meningoencephalitis Diagnosed Via Metagenomic Deep Sequencing of Cerebrospinal Fluid in a Renal Transplant Patient.

PubMed

Wilson, M R; Zimmermann, L L; Crawford, E D; Sample, H A; Soni, P R; Baker, A N; Khan, L M; DeRisi, J L

2017-03-01

Solid organ transplant patients are vulnerable to suffering neurologic complications from a wide array of viral infections and can be sentinels in the population who are first to get serious complications from emerging infections like the recent waves of arboviruses, including West Nile virus, Chikungunya virus, Zika virus, and Dengue virus. The diverse and rapidly changing landscape of possible causes of viral encephalitis poses great challenges for traditional candidate-based infectious disease diagnostics that already fail to identify a causative pathogen in approximately 50% of encephalitis cases. We present the case of a 14-year-old girl on immunosuppression for a renal transplant who presented with acute meningoencephalitis. Traditional diagnostics failed to identify an etiology. RNA extracted from her cerebrospinal fluid was subjected to unbiased metagenomic deep sequencing, enhanced with the use of a Cas9-based technique for host depletion. This analysis identified West Nile virus (WNV). Convalescent serum serologies subsequently confirmed WNV seroconversion. These results support a clear clinical role for metagenomic deep sequencing in the setting of suspected viral encephalitis, especially in the context of the high-risk transplant patient population. © 2016 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of American Society of Transplant Surgeons.

Structure of a Venezuelan equine encephalitis virus assembly intermediate isolated from infected cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lamb, Kristen; Lokesh, G.L.; Sherman, Michael

2010-10-25

Venezuelan equine encephalitis virus (VEEV) is a prototypical enveloped ssRNA virus of the family Togaviridae. To better understand alphavirus assembly, we analyzed newly formed nucleocapsid particles (termed pre-viral nucleocapsids) isolated from infected cells. These particles were intermediates along the virus assembly pathway, and ultimately bind membrane-associated viral glycoproteins to bud as mature infectious virus. Purified pre-viral nucleocapsids were spherical with a unimodal diameter distribution. The structure of one class of pre-viral nucleocapsids was determined with single particle reconstruction of cryo-electron microscopy images. These studies showed that pre-viral nucleocapsids assembled into an icosahedral structure with a capsid stoichiometry similar to themore » mature nucleocapsid. However, the individual capsomers were organized significantly differently within the pre-viral and mature nucleocapsids. The pre-viral nucleocapsid structure implies that nucleocapsids are highly plastic and undergo glycoprotein and/or lipid-driven rearrangements during virus self-assembly. This mechanism of self-assembly may be general for other enveloped viruses.« less

Antibodies generated by immunization with the NS1 protein of West Nile virus confer partial protection against lethal Japanese encephalitis virus challenge.

PubMed

Sun, EnCheng; Zhao, Jing; TaoYang; Xu, QingYuan; Qin, YongLi; Wang, WenShi; Wei, Peng; Wu, DongLai

2013-09-27

Japanese encephalitis virus (JEV) and West Nile virus (WNV) are two medically important flaviviruses that can cause severe hemorrhagic and encephalitic diseases in humans. Immune responses directed against the NS1 protein of flaviviruses can confer protection against lethal viral challenge. Previous studies have shown that the WNV NS1 protein harbors epitopes that elicit antibodies that cross react with JEV. Here we demonstrate that the WNV NS1 protein not only contains cross-reactive epitopes, but that the antibodies elicited by these cross-reactive epitopes provide partial protection against lethal JEV challenge in a mouse model. Mice immunized with WNV NS1 protein showed reduced morbidity and mortality following both intracerebral and intraperitoneal JEV challenge. WNV NS1 immunization attenuated the extent of lung pathology generated following JEV challenge, and delayed the appearance of other pathological findings including vascular cuffing. By screening and identifying the specific WNV NS1 protein-derived peptides recognized by serum antibodies elicited by immunization with WNV NS1 protein and by JEV challenge, we found after JEV challenge will induce several new epitopes, but which epitope primarily contribute to antibody-mediated cross protection need further evaluation. The knowledge and reagents generated in this study have potential applications in vaccine and subunit vaccine development for WNV and JEV. Copyright © 2013 Elsevier B.V. All rights reserved.

Virus signaling and apoptosis in the central nervous system infection.

PubMed

Perkins, Dana

2005-09-01

Viruses target the central nervous system (CNS) incidentally, due to complications of systemic infection, or specifically, by ascending via the axons of peripheral and cranial nerves. In the CNS, viruses cause acute disease (viz. encephalitis), latent infections or neurodegenerative pathology. Causation of acute disease or immune-mediated pathology, and virus involvement in the etiology of chronic neurodegenerative diseases depends, at least in part, on the ability to commander signaling pathways. Better understanding of these virus-host cell interactions will help identify molecular targets for the development of improved therapeutic strategies.

The zoonotic flaviviruses of southern, south-eastern and eastern Asia, and Australasia: the potential for emergent viruses.

PubMed

Mackenzie, J S; Williams, D T

2009-08-01

The genus Flaviviridae comprises about 70 members, of which about 30 are found in southern, south-eastern and eastern Asia and Australasia. These include major pathogens such as Japanese encephalitis (JE), West Nile (WN), Murray Valley encephalitis (MVE), tick-borne encephalitis, Kyasanur Forest disease virus, and the dengue viruses. Other members are known to be associated with mild febrile disease in humans, or with no known disease. In addition, novel flaviviruses continue to be discovered, as demonstrated recently by New Mapoon virus in Australia, Sitiawan virus in Malaysia, and ThCAr virus in Thailand. About 19 of these viruses are mosquito-borne, six are tick-borne, and four have no known vector and represent isolates from rodents or bats. Evidence from phylogenetic studies suggest that JE, MVE and Alfuy viruses probably emerged in the Malaya-Indonesian region from an African progenitor virus, possibly a virus related to Usutu virus. WN virus, however, is believed to have emerged in Africa, and then dispersed through avian migration. Evidence suggests that there are at least seven genetic lineages of WN virus, of which lineage 1b spread to Australasia as Kunjin virus, lineages 1a and 5 spread to India, and lineage 6 spread to Malaysia. Indeed, flaviviruses have a propensity to spread and emerge in new geographic areas, and they represent a potential source for new disease emergence. Many of the factors associated with disease emergence are present in the region, such as changes in land use and deforestation, increasing population movement, urbanization, and increasing trade. Furthermore, because of their ecology and dependence on climate, there is a strong likelihood that global warming may significantly increase the potential for disease emergence and/or spread.

Peromyscus leucopus mouse brain transcriptome response to Powassan virus infection.

PubMed

Mlera, Luwanika; Meade-White, Kimberly; Dahlstrom, Eric; Baur, Rachel; Kanakabandi, Kishore; Virtaneva, Kimmo; Porcella, Stephen F; Bloom, Marshall E

2018-02-01

Powassan virus (POWV) is a tick-borne Flavivirus responsible for life-threatening encephalitis in North America and some regions of Russia. The ticks that have been reported to transmit the virus belong to the Ixodes species, and they feed on small-to-medium-sized mammals, such as Peromyscus leucopus mice, skunks, and woodchucks. We previously developed a P. leucopus mouse model of POWV infection, and the model is characterized by a lack of clinical signs of disease following intraperitoneal or intracranial inoculation. However, intracranial inoculation results in mild subclinical encephalitis from 5 days post infection (dpi), but the encephalitis resolves by 28 dpi. We used RNA sequencing to profile the P. leucopus mouse brain transcriptome at different time points after intracranial challenge with POWV. At 24 h post infection, 42 genes were significantly differentially expressed and the number peaked to 232 at 7 dpi before declining to 31 at 28 dpi. Using Ingenuity Pathway Analysis, we determined that the genes that were significantly expressed from 1 to 15 dpi were mainly associated with interferon signaling. As a result, many interferon-stimulated genes (ISGs) were upregulated. Some of the ISGs include an array of TRIMs (genes encoding tripartite motif proteins). These results will be useful for the identification of POWV restriction factors.

[Herpetic encephalitis: a clinical case].

PubMed

Dryhant, L P; Sereda, V H; Kushpiĭ, O V; Tkachenko, V V; Kravchuk, N A; Inhula, N I; Sizina, A V; Sachko, Iu Iu; Andrusenko, A S; Tytenko, Iu I; Babirad, A M

2012-01-01

An example of diagnostics and treatment of patient is in-process made with herpetic encephalitis. It is well-proven in researches, that a herpetic encephalitis is 11.5% among sharp encephalitises. Morbidity is sporadic, some researchers specify on an increase its spring. An infection can be passed tiny and pin a way. Seasonal vibrations are not incident to the herpetic encephalitis. Two peaks of morbidity are on 5-30 years and age more senior 50 years. More than in 95% cases the virus of simple herpes of type serves as an exciter of herpetic encephalitis 1. A characteristic triad of herpetic encephalitis is the sharp feverish beginning, development of cramps of dzheksonovskogo type and violation of consciousness, developing usually after a brief respirator infection. Sometimes sudden development of cramps and loss of consciousness is preceded a fever. Example of such development of disease is made an in our work.

Diagnostic Approach to Viral Acute Encephalitis Syndrome (AES) in Paediatric Age Group: A Study from New Delhi.

PubMed

Goel, Shipra; Chakravarti, Anita; Mantan, Mukta; Kumar, Surinder; Ashraf, Md Anzar

2017-09-01

Acute Encephalitis Syndrome has heralded the emergence of multiple virulent pathogens, which may result in severe morbidity and mortality. In India, encephalitis is not notified and there has been a dearth of analysis for trends in encephalitis death rates and causation. A downward trend has been observed in encephalitis deaths, due to 'known' causes, which can be largely explained by improvement in diagnostic, treatment, and prevention methods. There is still a very high proportion of encephalitis deaths in developing countries, where the aetiological diagnosis of the pathogen is not established and thus, lies the importance of monitoring encephalitis morbidity and mortality with a view to improve pathogen diagnosis and identify emerging infectious diseases. To formulate a diagnostic approach to viral acute encephalitis syndrome in paediatric age group. A cross-sectional study including 50 paediatric patients, clinically diagnosed with acute encephalitis syndrome using WHO criteria was conducted. The CSF of all the patients was evaluated to diagnose the aetiology for viral pathogens. ELISA was used for diagnosing Japanese encephalitis and dengue encephalitis; and multiplex real time PCR was used for detecting HSV-1, HSV-2, Varicella zoster virus, Mumps virus, Enterovirus and Parechovirus. Confirmed diagnosis was established in 11 (22%) of 50 cases. A confirmed or probable viral agent of encephalitis was found in 7 (14%), bacterial agent was found in 2 (4%), non-infectious aetiology was found in 2 (4%). Fatal outcome was independently associated with patient age. Despite extensive testing, the aetiologies of more than three fourth of the cases remains elusive. Nevertheless the result from the present study may be useful for future design of early diagnosis and treatment of the disease. New strategies for pathogen identification and continued analysis of clinical features and case histories should help us improve our ability to diagnose, treat and prevent encephalitis.

Flavivirus-induced antibody cross-reactivity

PubMed Central

Mansfield, Karen L.; Horton, Daniel L.; Johnson, Nicholas; Li, Li; Barrett, Alan D. T.; Smith, Derek J.; Galbraith, Sareen E.; Solomon, Tom

2011-01-01

Dengue viruses (DENV) cause countless human deaths each year, whilst West Nile virus (WNV) has re-emerged as an important human pathogen. There are currently no WNV or DENV vaccines licensed for human use, yet vaccines exist against other flaviviruses. To investigate flavivirus cross-reactivity, sera from a human cohort with a history of vaccination against tick-borne encephalitis virus (TBEV), Japanese encephalitis virus (JEV) and yellow fever virus (YFV) were tested for antibodies by plaque reduction neutralization test. Neutralization of louping ill virus (LIV) occurred, but no significant neutralization of Murray Valley encephalitis virus was observed. Sera from some individuals vaccinated against TBEV and JEV neutralized WNV, which was enhanced by YFV vaccination in some recipients. Similarly, some individuals neutralized DENV-2, but this was not significantly influenced by YFV vaccination. Antigenic cartography techniques were used to generate a geometric illustration of the neutralization titres of selected sera against WNV, TBEV, JEV, LIV, YFV and DENV-2. This demonstrated the individual variation in antibody responses. Most sera had detectable titres against LIV and some had titres against WNV and DENV-2. Generally, LIV titres were similar to titres against TBEV, confirming the close antigenic relationship between TBEV and LIV. JEV was also antigenically closer to TBEV than WNV, using these sera. The use of sera from individuals vaccinated against multiple pathogens is unique relative to previous applications of antigenic cartography techniques. It is evident from these data that notable differences exist between amino acid sequence identity and mapped antigenic relationships within the family Flaviviridae. PMID:21900425

Flavivirus-induced antibody cross-reactivity.

PubMed

Mansfield, Karen L; Horton, Daniel L; Johnson, Nicholas; Li, Li; Barrett, Alan D T; Smith, Derek J; Galbraith, Sareen E; Solomon, Tom; Fooks, Anthony R

2011-12-01

Dengue viruses (DENV) cause countless human deaths each year, whilst West Nile virus (WNV) has re-emerged as an important human pathogen. There are currently no WNV or DENV vaccines licensed for human use, yet vaccines exist against other flaviviruses. To investigate flavivirus cross-reactivity, sera from a human cohort with a history of vaccination against tick-borne encephalitis virus (TBEV), Japanese encephalitis virus (JEV) and yellow fever virus (YFV) were tested for antibodies by plaque reduction neutralization test. Neutralization of louping ill virus (LIV) occurred, but no significant neutralization of Murray Valley encephalitis virus was observed. Sera from some individuals vaccinated against TBEV and JEV neutralized WNV, which was enhanced by YFV vaccination in some recipients. Similarly, some individuals neutralized DENV-2, but this was not significantly influenced by YFV vaccination. Antigenic cartography techniques were used to generate a geometric illustration of the neutralization titres of selected sera against WNV, TBEV, JEV, LIV, YFV and DENV-2. This demonstrated the individual variation in antibody responses. Most sera had detectable titres against LIV and some had titres against WNV and DENV-2. Generally, LIV titres were similar to titres against TBEV, confirming the close antigenic relationship between TBEV and LIV. JEV was also antigenically closer to TBEV than WNV, using these sera. The use of sera from individuals vaccinated against multiple pathogens is unique relative to previous applications of antigenic cartography techniques. It is evident from these data that notable differences exist between amino acid sequence identity and mapped antigenic relationships within the family Flaviviridae.

Post-licensure, phase IV, safety study of a live attenuated Japanese encephalitis recombinant vaccine in children in Thailand.

PubMed

Chotpitayasunondh, Tawee; Pruekprasert, Pornpimol; Puthanakit, Thanyawee; Pancharoen, Chitsanu; Tangsathapornpong, Auchara; Oberdorfer, Peninnah; Kosalaraksa, Pope; Prommalikit, Olarn; Tangkittithaworn, Suwimon; Kerdpanich, Phirangkul; Techasaensiri, Chonnamet; Korejwo, Joanna; Chuenkitmongkol, Sunate; Houillon, Guy

2017-01-05

Japanese encephalitis is a mosquito-borne viral disease endemic in most countries in Asia. A recombinant live, attenuated Japanese encephalitis virus vaccine, JE-CV, is licensed in 14 countries, including Thailand, for the prevention of Japanese encephalitis in adults and children. This was a prospective, phase IV, open-label, multicentre, safety study of JE-CV conducted from November 2013 to April 2015, to evaluate rare serious adverse events (AEs). JE-CV was administered to 10,000 healthy children aged 9months to <5years in Thailand as a primary (Group 1) or booster (Group 2) vaccination. Serious AEs (SAEs), including AEs of special interest, up to 60days after administration were evaluated. Immediate Grade 3 systemic AEs up to 30min after JE-CV administration were also described. The median age of participants was 1.1years in Group 1 and 3.8years in Group 2. SAEs were reported in 204 (3.0%) participants in Group 1 and 59 (1.9%) participants in Group 2. Among a total of 294 SAEs in 263 participants, only three events occurring in two participants were considered related to vaccination. All three cases were moderate urticaria, none of which met the definition of AEs of special interest for hypersensitivity. AEs of special interest were reported in 28 (0.4%) participants in Group 1 and 4 (0.1%) participants in Group 2; none were considered related to vaccination. Febrile convulsion was the most frequently reported AE of special interest: 25 (0.4%) participants in Group 1; and 2 (<0.1%) in Group 2. There were no cases of Japanese encephalitis reported. No Grade 3 immediate systemic AEs were reported after any JE-CV vaccination. Our study did not identify any new safety concerns with JE-CV and confirms its good safety profile. This study was registered on www.clinicaltrials.gov (NCT01981967; Universal Trial Number: U1111-1127-7052). Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

In vivo Expression of Inducible Nitric Oxide Synthase in Experimentally Induced Neurologic Diseases

NASA Astrophysics Data System (ADS)

Koprowski, Hilary; Zheng, Yong Mu; Heber-Katz, Ellen; Fraser, Nigel; Rorke, Lucy; Fu, Zhen Fang; Hanlon, Cathleen; Dietzschold, Bernhard

1993-04-01

The purpose of this study was to investigate the induction of inducible nitric oxide synthase (iNOS) mRNA in the brain tissue of rats and mice under the following experimental conditions: in rats infected with borna disease virus and rabies virus, in mice infected with herpes simplex virus, and in rats after the induction of experimental allergic encephalitis. The results showed that iNOS mRNA, normally nondetectable in the brain, was present in animals after viral infection or after induction of experimental allergic encephalitis. The induction of iNOS mRNA coincided with the severity of clinical signs and in some cases with the presence of inflammatory cells in the brain. The results indicate that nitric oxide produced by cells induced by iNOS may be the toxic factor accounting for cell damage and this may open the door to approaches to the study of the pathogenesis of neurological diseases.

Alpha-Synuclein Expression Restricts RNA Viral Infections in the Brain.

PubMed

Beatman, Erica L; Massey, Aaron; Shives, Katherine D; Burrack, Kristina S; Chamanian, Mastooreh; Morrison, Thomas E; Beckham, J David

2015-12-30

We have discovered that native, neuronal expression of alpha-synuclein (Asyn) inhibits viral infection, injury, and disease in the central nervous system (CNS). Enveloped RNA viruses, such as West Nile virus (WNV), invade the CNS and cause encephalitis, yet little is known about the innate neuron-specific inhibitors of viral infections in the CNS. Following WNV infection of primary neurons, we found that Asyn protein expression is increased. The infectious titer of WNV and Venezuelan equine encephalitis virus (VEEV) TC83 in the brains of Asyn-knockout mice exhibited a mean increase of 10(4.5) infectious viral particles compared to the titers in wild-type and heterozygote littermates. Asyn-knockout mice also exhibited significantly increased virus-induced mortality compared to Asyn heterozygote or homozygote control mice. Virus-induced Asyn localized to perinuclear, neuronal regions expressing viral envelope protein and the endoplasmic reticulum (ER)-associated trafficking protein Rab1. In Asyn-knockout primary neuronal cultures, the levels of expression of ER signaling pathways, known to support WNV replication, were significantly elevated before and during viral infection compared to those in Asyn-expressing primary neuronal cultures. We propose a model in which virus-induced Asyn localizes to ER-derived membranes, modulates virus-induced ER stress signaling, and inhibits viral replication, growth, and injury in the CNS. These data provide a novel and important functional role for the expression of native alpha-synuclein, a protein that is closely associated with the development of Parkinson's disease. Neuroinvasive viruses such as West Nile virus are able to infect neurons and cause severe disease, such as encephalitis, or infection of brain tissue. Following viral infection in the central nervous system, only select neurons are infected, implying that neurons exhibit innate resistance to viral infections. We discovered that native neuronal expression of alpha-synuclein inhibited viral infection in the central nervous system. When the gene for alpha-synuclein was deleted, mice exhibited significantly decreased survival, markedly increased viral growth in the brain, and evidence of increased neuron injury. Virus-induced alpha-synuclein localized to intracellular neuron membranes, and in the absence of alpha-synuclein expression, specific endoplasmic reticulum stress signaling events were significantly increased. We describe a new neuron-specific inhibitor of viral infections in the central nervous system. Given the importance of alpha-synuclein as a cause of Parkinson's disease, these data also ascribe a novel functional role for the native expression of alpha-synuclein in the CNS. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Psychosis in a 15-Year-Old Female with Herpes Simplex Encephalitis in a Background of Mannose-Binding Lecithin Deficiency.

PubMed

Asogwa, Kenneth; Buabeng, Kwame; Kaur, Amarjit

2017-01-01

Historically, psychotic disorder has been associated with viral infection. Herpes simplex infections and Epstein-Barr virus (EBV) among other viral infections have been implicated in psychotic disorder. Of note in this case report is psychotic disorder that occurred following reactivation of herpes simplex infection in a background of mannose-binding lecithin (MBL) deficiency, childhood EBV infection, and severe psychosocial stress. Herpes simplex encephalitis (HSE) remains a significant cause of morbidity and mortality despite advancement in its treatment with intravenous acyclovir. Many studies have reported psychiatric and neurological manifestation of herpes simplex infection following primary or reactivated infection, while others suggest milder clinical course of herpes simplex encephalitis in a background of immunosuppression. Another contributory factor to psychotic disorder in this case is childhood EBV exposure which has been reported to increase the risk of psychosis in adolescence and adulthood. This case report describes a 15-year-old female with MBL deficiency who presented with psychosis caused by reactivated herpes simplex infection and had good clinical recovery. Based on childhood Epstein-Barr virus exposure and psychosis in adolescence (current case), she is at increased risk of psychotic disorder in adulthood, which underscores the importance of long-term monitoring.

Tick Infestation Risk and Borrelia burgdorferi s.l. Infection-Induced Increase in Host-Finding Efficacy of Female Ixodes ricinus Under Natural Conditions

DTIC Science & Technology

2008-02-14

worldwide, only a few are vaccine -preventable (e.g., tick-borne encephalitis, yellow fever, Japanese encephalitis, and plague). For this reason...western Germany underscore the considerable risk of acquiring Lyme borreliosis in Central Europe. Since no licensed vaccine exists for Lyme borreliosis...Acknowledgements We thank Marco Isack, Sabine Barz, Thorsten Lange, Bernd Bocklet and Dirk Hiller for their assistance with fieldwork. TibMolBiol

Microbial study of meningitis and encephalitis cases.

PubMed

Selim, Heba S; El-Barrawy, Mohamed A; Rakha, Magda E; Yingst, Samuel L; Baskharoun, Magda F

2007-01-01

Meningitis and/or encephalitis can pose a serious public health problem especially during outbreaks. A rapid and accurate diagnosis is important for effective earlier treatment. This study aimed to identify the possible microbial causes of meningitis and/or encephalitis cases. CSF and serum samples were collected from 322 patients who had signs and symptoms suggestive of meningitis and/or encephalitis. Out of 250 cases with confirmed clinical diagnosis, 83 (33.2%) were definitely diagnosed as bacterial meningitis and/or encephalitis cases (by using CSF culture, biochemical tests, latex agglutination test, and CSF stain), 17 (6.8%) were definitely diagnosed as having viral causes ( by viral isolation on tissue culture, PCR and ELISA), and one (0.4%) was diagnosed as fungal meningitis case (by India ink stain, culture, and biochemical tests). Also, there was one encephalitis case with positive serum ELISA IgM antibodies against Sandfly scilian virus. N. meningitidis, S. pneumonia and M. tuberculosis were the most frequently detected bacterial agents, while Enteroviruses, herpes simplex viruses and varicella zoster viruses were the most common viral agents encountered. Further studies are needed to assess the role of different microbial agents in CNS infections and their effective methods of diagnosis.

78 FR 22268 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panels (SEP): Initial Review

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-15

...; Strengthening Surveillance for Japanese Encephalitis in India, FOA GH13-004; and Research and Technical... GH13-003; Strengthening Surveillance for Japanese Encephalitis in India, FOA GH13-004; and Research and... of Karnataka and Kerala, India, FOA GH13-003; Strengthening Surveillance for Japanese Encephalitis in...

Development of simple and rapid assay to detect viral RNA of tick-borne encephalitis virus by reverse transcription-loop-mediated isothermal amplification.

PubMed

Hayasaka, Daisuke; Aoki, Kotaro; Morita, Kouichi

2013-03-04

Tick-borne encephalitis virus (TBEV) is a causative agent of acute central nervous system disease in humans. It has three subtypes, far eastern (FE), Siberian (Sib) and European (Eu) subtypes, which are distributed over a wide area of Europe and Asia. The objective of this study was to develop a simple and rapid assay for the detection of TBEV RNA by using reverse-transcriptase loop-mediated isothermal amplification (RT-LAMP) method that can differentiate the three subtypes of TBEV and can be used for clinical diagnosis and epidemiological study. Primers for TBEV-specific and subtype-specific RT-LAMP assay were designed to target the consensus sequence in NS1 of all subtypes and the consensus sequence in the E gene of each subtype, respectiveluy. In vitro transcribed RNA of Oshima strain that belongs to FE subtype was serially diluted and used to examine the sensitivity of the assay. Cross-reactivity of subtype-specific RT-LAMP assay was tested by using the RNA of Oshima and Sofjin (FE), IR-99 (Sib) and Hochosterwitz (Eu) strains. RNA extracted from the mixtures of TBEV and ticks, and of TBEV and human blood, and the mouse tissues infected with TBEV, were evaluated in the assay. Positive amplification was observed by real-time monitoring of turbidity and by visual detection of color change. The sensitivity of TBEV-specific RT-LAMP assay was 102 copies of target RNA per reaction volume. FE-specific RT-LAMP assay amplified viral genes of Oshima and Sofjin strains but not of IR-99 and Hochosterwitz strains, and of Japanese encephalitis virus. RT-LAMP assay for Sib and for Eu specifically amplified viral genes of IR-99 and Hochosterwitz strains, respectively. We also showed that tick or human blood extract did not inhibit the amplification of viral gene during the assay. Furthermore, we confirmed that the TBEV RT-LAMP could detect virus RNA from peripheral and central nervous system tissues of laboratory mice infected with TBEV. TBEV RT-LAMP assay offers a sensitive, specific, rapid and easy-to-handle method for the detection of TBEV RNA in tick samples and this may be applied in the clinical samples collected from TBE-suspected patients.

Recovery of West Nile Virus Envelope Protein Domain III Chimeras with Altered Antigenicity and Mouse Virulence

PubMed Central

McAuley, Alexander J.; Torres, Maricela; Plante, Jessica A.; Huang, Claire Y.-H.; Bente, Dennis A.

2016-01-01

ABSTRACT Flaviviruses are positive-sense, single-stranded RNA viruses responsible for millions of human infections annually. The envelope (E) protein of flaviviruses comprises three structural domains, of which domain III (EIII) represents a discrete subunit. The EIII gene sequence typically encodes epitopes recognized by virus-specific, potently neutralizing antibodies, and EIII is believed to play a major role in receptor binding. In order to assess potential interactions between EIII and the remainder of the E protein and to assess the effects of EIII sequence substitutions on the antigenicity, growth, and virulence of a representative flavivirus, chimeric viruses were generated using the West Nile virus (WNV) infectious clone, into which EIIIs from nine flaviviruses with various levels of genetic diversity from WNV were substituted. Of the constructs tested, chimeras containing EIIIs from Koutango virus (KOUV), Japanese encephalitis virus (JEV), St. Louis encephalitis virus (SLEV), and Bagaza virus (BAGV) were successfully recovered. Characterization of the chimeras in vitro and in vivo revealed differences in growth and virulence between the viruses, with in vivo pathogenesis often not being correlated with in vitro growth. Taken together, the data demonstrate that substitutions of EIII can allow the generation of viable chimeric viruses with significantly altered antigenicity and virulence. IMPORTANCE The envelope (E) glycoprotein is the major protein present on the surface of flavivirus virions and is responsible for mediating virus binding and entry into target cells. Several viable West Nile virus (WNV) variants with chimeric E proteins in which the putative receptor-binding domain (EIII) sequences of other mosquito-borne flaviviruses were substituted in place of the WNV EIII were recovered, although the substitution of several more divergent EIII sequences was not tolerated. The differences in virulence and tissue tropism observed with the chimeric viruses indicate a significant role for this sequence in determining the pathogenesis of the virus within the mammalian host. Our studies demonstrate that these chimeras are viable and suggest that such recombinant viruses may be useful for investigation of domain-specific antibody responses and the more extensive definition of the contributions of EIII to the tropism and pathogenesis of WNV or other flaviviruses. PMID:26912625

Recovery of West Nile Virus Envelope Protein Domain III Chimeras with Altered Antigenicity and Mouse Virulence.

PubMed

McAuley, Alexander J; Torres, Maricela; Plante, Jessica A; Huang, Claire Y-H; Bente, Dennis A; Beasley, David W C

2016-05-01

Flaviviruses are positive-sense, single-stranded RNA viruses responsible for millions of human infections annually. The envelope (E) protein of flaviviruses comprises three structural domains, of which domain III (EIII) represents a discrete subunit. The EIII gene sequence typically encodes epitopes recognized by virus-specific, potently neutralizing antibodies, and EIII is believed to play a major role in receptor binding. In order to assess potential interactions between EIII and the remainder of the E protein and to assess the effects of EIII sequence substitutions on the antigenicity, growth, and virulence of a representative flavivirus, chimeric viruses were generated using the West Nile virus (WNV) infectious clone, into which EIIIs from nine flaviviruses with various levels of genetic diversity from WNV were substituted. Of the constructs tested, chimeras containing EIIIs from Koutango virus (KOUV), Japanese encephalitis virus (JEV), St. Louis encephalitis virus (SLEV), and Bagaza virus (BAGV) were successfully recovered. Characterization of the chimeras in vitro and in vivo revealed differences in growth and virulence between the viruses, within vivo pathogenesis often not being correlated within vitro growth. Taken together, the data demonstrate that substitutions of EIII can allow the generation of viable chimeric viruses with significantly altered antigenicity and virulence. The envelope (E) glycoprotein is the major protein present on the surface of flavivirus virions and is responsible for mediating virus binding and entry into target cells. Several viable West Nile virus (WNV) variants with chimeric E proteins in which the putative receptor-binding domain (EIII) sequences of other mosquito-borne flaviviruses were substituted in place of the WNV EIII were recovered, although the substitution of several more divergent EIII sequences was not tolerated. The differences in virulence and tissue tropism observed with the chimeric viruses indicate a significant role for this sequence in determining the pathogenesis of the virus within the mammalian host. Our studies demonstrate that these chimeras are viable and suggest that such recombinant viruses may be useful for investigation of domain-specific antibody responses and the more extensive definition of the contributions of EIII to the tropism and pathogenesis of WNV or other flaviviruses. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Identification of host genes leading to West Nile virus encephalitis in mice brain using RNA-seq analysis

PubMed Central

Kumar, Mukesh; Belcaid, Mahdi; Nerurkar, Vivek R.

2016-01-01

Differential host responses may be critical determinants of distinct pathologies of West Nile virus (WNV) NY99 (pathogenic) and WNV Eg101 (non-pathogenic) strains. We employed RNA-seq technology to analyze global differential gene expression in WNV-infected mice brain and to identify the host cellular factors leading to lethal encephalitis. We identified 1,400 and 278 transcripts, which were differentially expressed after WNV NY99 and WNV Eg101 infections, respectively, and 147 genes were common to infection with both the viruses. Genes that were up-regulated in infection with both the viruses were mainly associated with interferon signaling. Genes associated with inflammation and cell death/apoptosis were only expressed after WNV NY99 infection. We demonstrate that differences in the activation of key pattern recognition receptors resulted in the induction of unique innate immune profiles, which corresponded with the induction of interferon and inflammatory responses. Pathway analysis of differentially expressed genes indicated that after WNV NY99 infection, TREM-1 mediated activation of toll-like receptors leads to the high inflammatory response. In conclusion, we have identified both common and specific responses to WNV NY99 and WNV Eg101 infections as well as genes linked to potential resistance to infection that may be targets for therapeutics. PMID:27211830

West Nile Virus and Other Nationally Notifiable Arboviral Diseases - United States, 2014.

PubMed

Lindsey, Nicole P; Lehman, Jennifer A; Staples, J Erin; Fischer, Marc

2015-09-04

Arthropod-borne viruses (arboviruses) are transmitted to humans primarily through the bites of infected mosquitoes and ticks. West Nile virus (WNV) is the leading cause of domestically acquired arboviral disease in the United States (1). However, several other arboviruses also cause sporadic cases and seasonal outbreaks. This report summarizes surveillance data reported to CDC in 2014 for WNV and other nationally notifiable arboviruses, excluding dengue. Forty-two states and the District of Columbia (DC) reported 2,205 cases of WNV disease. Of these, 1,347 (61%) were classified as WNV neuroinvasive disease (e.g., meningitis, encephalitis, or acute flaccid paralysis), for a national incidence of 0.42 cases per 100,000 population. After WNV, the next most commonly reported cause of arboviral disease was La Crosse virus (80 cases), followed by Jamestown Canyon virus (11), St. Louis encephalitis virus (10), Powassan virus (8), and Eastern equine encephalitis virus (8). WNV and other arboviruses cause serious illness in substantial numbers of persons each year. Maintaining surveillance programs is important to help direct prevention activities.

Enhancing the antiviral potency of ER α-glucosidase inhibitor IHVR-19029 against hemorrhagic fever viruses in vitro and in vivo.

PubMed

Ma, Julia; Zhang, Xuexiang; Soloveva, Veronica; Warren, Travis; Guo, Fang; Wu, Shuo; Lu, Huagang; Guo, Jia; Su, Qing; Shen, Helen; Solon, Eric; Comunale, Mary Ann; Mehta, Anand; Guo, Ju-Tao; Bavari, Sina; Du, Yanming; Block, Timothy M; Chang, Jinhong

2018-02-01

Targeting host functions essential for viral replication has been considered as a broad spectrum and resistance-refractory antiviral approach. However, only a few host functions have, thus far, been validated as broad-spectrum antiviral targets in vivo. ER α-glucosidases I and II have been demonstrated to be essential for the morphogenesis of many enveloped viruses, including members from four families of viruses causing hemorrhagic fever. In vivo antiviral efficacy of various iminosugar-based ER α-glucosidase inhibitors has been reported in animals infected with Dengue, Japanese encephalitis, Ebola, Marburg and influenza viruses. Herein, we established Huh7.5-derived cell lines with ER α-glucosidase I or II knockout using CRISPR/Cas9 and demonstrated that the replication of Dengue, Yellow fever and Zika viruses was reduced by only 1-2 logs in the knockout cell lines. The results clearly indicate that only a partial suppression of viral replication can possibly be achieved with a complete inhibition of ER-α-glucosidases I or II by their inhibitors. We therefore explore to improve the antiviral efficacy of a lead iminosugar IHVR-19029 through combination with another broad-spectrum antiviral agent, favipiravir (T-705). Indeed, combination of IHVR-19029 and T-705 synergistically inhibited the replication of Yellow fever and Ebola viruses in cultured cells. Moreover, in a mouse model of Ebola virus infection, combination of sub-optimal doses of IHVR-19029 and T-705 significantly increased the survival rate of infected animals. We have thus proved the concept of combinational therapeutic strategy for the treatment of viral hemorrhagic fevers with broad spectrum host- and viral- targeting antiviral agents. Copyright © 2017 Elsevier B.V. All rights reserved.

Encephalitis - Multiple Languages

MedlinePlus

... dialect) (繁體中文) Expand Section Vaccine Information Statement (VIS) -- Japanese Encephalitis Vaccine: What You Need to Know - English PDF Vaccine Information Statement (VIS) -- Japanese Encephalitis Vaccine: What You Need to Know - 繁體中文 ( ...

Diagnosis of herpes simplex virus infection by immunofluorescence.

PubMed Central

Taber, L H; Brasier, F; Couch, R B; Greenberg, S B; Jones, D; Knight, V

1976-01-01

The utility of the indirect immunofluorescent antibody (IFA) technique for diagnosis of herpes simplex virus (HSV) infection was examined by testing specimens for this agent from 31 patients with encephalitis or meningitis, 17 with conjunctivitis, 19 with genital disease, and 1 with genital disease and meningitis. Brain biopsy tissue from four patients with encephalitis was positive by IFA and virus culture for HSV. Leukocytes in cerebrospinal fluid from these four patients and one with HSV meningitis were also positive by IFA, but virus isolation attempts on the fluid were all negative. Conjunctival scrapings from two patients with conjunctivitis were positive for HSV by both IFA and virus culture. Eleven of 12 culture-positive lesions of herpes progenitalis were positive by IFA, and 1 dark field-positive syphilitic chancre was also positive for HSV by both IFA and culture. Evidence for specificity of the results was provided by internal controls in each test and negative results from patients with other diagnoses. Thus, the IFA technique constituted a rapid, sensitive, and specific diagnostic method for the diagnosis of HSV infections. PMID:178689

N-Desmethylclozapine, Fluoxetine, and Salmeterol Inhibit Postentry Stages of the Dengue Virus Life Cycle.

PubMed

Medigeshi, Guruprasad R; Kumar, Rinki; Dhamija, Ekta; Agrawal, Tanvi; Kar, Meenakshi

2016-11-01

Around 10,000 people die each year due to severe dengue disease, and two-thirds of the world population lives in a region where dengue disease is endemic. There has been remarkable progress in dengue virus vaccine development; however, there are no licensed antivirals for dengue disease, and none appear to be in clinical trials. We took the approach of repositioning approved drugs for anti-dengue virus activity by screening a library of pharmacologically active compounds. We identified N-desmethylclozapine, fluoxetine hydrochloride, and salmeterol xinafoate as dengue virus inhibitors based on reductions in the numbers of infected cells and viral titers. Dengue virus RNA levels were diminished in inhibitor-treated cells, and this effect was specific to dengue virus, as other flaviviruses, such as Japanese encephalitis virus and West Nile virus, or other RNA viruses, such as respiratory syncytial virus and rotavirus, were not affected by these inhibitors. All three inhibitors specifically inhibited dengue virus replication with 50% inhibitory concentrations (IC 50 s) in the high-nanomolar range. Estimation of negative-strand RNA intermediates and time-of-addition experiments indicated that inhibition was occurring at a postentry stage, most probably at the initiation of viral RNA replication. Finally, we show that inhibition is most likely due to the modulation of the endolysosomal pathway and induction of autophagy. Copyright © 2016 Medigeshi et al.

A structural perspective of the flavivirus life cycle.

PubMed

Mukhopadhyay, Suchetana; Kuhn, Richard J; Rossmann, Michael G

2005-01-01

Dengue, Japanese encephalitis, West Nile and yellow fever belong to the Flavivirus genus, which is a member of the Flaviviridae family. They are human pathogens that cause large epidemics and tens of thousands of deaths annually in many parts of the world. The structural organization of these viruses and their associated structural proteins has provided insight into the molecular transitions that occur during the viral life cycle, such as assembly, budding, maturation and fusion. This review focuses mainly on structural studies of dengue virus.

West Nile virus: North American experience

USGS Publications Warehouse

Hofmeister, Erik K.

2011-01-01

West Nile virus, a mosquito-vectored flavivirus of the Japanese encephalitis serogroup, was first detected in North America following an epizootic in the New York City area in 1999. In the intervening 11 years since the arrival of the virus in North America, it has crossed the contiguous USA, entered the Canadian provinces bordering the USA, and has been reported in the Caribbean islands, Mexico, Central America and, more recently, South America. West Nile virus has been reported in over 300 species of birds in the USA and has caused the deaths of thousands of birds, local population declines of some avian species, the clinical illness and deaths of thousands of domestic horses, and the clinical disease in over 30 000 Americans and the deaths of over 1000. Prior to the emergence of West Nile virus in North America, St. Louis encephalitis virus and Dengue virus were the only other known mosquito-transmitted flaviviruses in North America capable of causing human disease. This review will discuss the North American experience with mosquito-borne flavivirus prior to the arrival of West Nile virus, the entry and spread of West Nile virus in North America, effects on wild bird populations, genetic changes in the virus, and the current state of West Nile virus transmission.

Herpesvirus-associated central nervous system diseases after allogeneic hematopoietic stem cell transplantation.

PubMed

Wu, Meiqing; Huang, Fen; Jiang, Xinmiao; Fan, Zhiping; Zhou, Hongsheng; Liu, Can; Jiang, Qianli; Zhang, Yu; Zhao, Ke; Xuan, Li; Zhai, Xiao; Zhang, Fuhua; Yin, Changxin; Sun, Jing; Feng, Ru; Liu, Qifa

2013-01-01

Herpesvirus infections of the central nervous system (CNS) are associated with encephalitis/myelitis and lymphoproliferative diseases in immunocompromised individuals. As of now, data of herpesvirus-associated CNS diseases in transplant recipients is limited. Hence, in this prospective study, we investigated the incidence of herpesvirus-associated CNS diseases and explored the diagnosis of these diseases in 281 allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Herpesvirus-DNA and cerebrospinal fluid (CSF) cells were sampled from 58 recipients with herpesvirus-associated diseases or with unexplainable CNS manifestations. Results showed that 23 patients were diagnosed as herpesvirus-associated CNS diseases, including 15 Epstein-Barr virus (EBV)-associated diseases (4 encephalitis and 11 lymphoproliferative diseases), 5 herpes simplex virus type 1 encephalitis, 2 cytomegalovirus encephalitis/myelitis and 1 varicella zoster virus encephalitis. The median time of diseases onset was 65 (range 22-542) days post-transplantation. The 3-year cumulative incidence of herpesvirus-associated encephalitis/myelitis and post-transplant lymphoproliferative disorder (PTLD) was 6.3% ± 1.9% and 4.1% ± 1.2%, respectively. Of the evaluable cases, CSF cells mainly consisted of CD19(+)CD20(+) B cells (7/11) and had clonal rearrangement of immunoglobulin genes (3/11) in patients with CNS-PTLD. On the contrary, in patients with encephalitis/myelitis, CSF cells were comprised of different cell populations and none of the gene rearrangement was detected. Herpesvirus-associated CNS diseases are common in the early stages of allo-HSCT, wherein EBV is the most frequent causative virus. The immunophenotypic and clonal analysis of CSF cells might be helpful in the differential diagnosis between encephalitis and lymphoproliferative diseases.

Monocyte/macrophage trafficking in acquired immunodeficiency syndrome encephalitis: lessons from human and nonhuman primate studies.

PubMed

Fischer-Smith, Tracy; Bell, Christie; Croul, Sidney; Lewis, Mark; Rappaport, Jay

2008-08-01

Here the authors discuss evidence in human and animal models supporting two opposing views regarding the pathogenesis of human immunodeficiency virus (HIV) in the central nervous system (CNS): (1) HIV infection in the CNS is a compartmentalized infection, with the virus-infected macrophages entering the CNS early, infecting resident microglia and astrocytes, and achieving a state of latency with evolution toward a fulminant CNS infection late in the course of disease; or alternatively, (2) events in the periphery lead to altered monocyte/macrophage (MPhi) homeostasis, with increased CNS invasion of infected and/or uninfected MPhis. Here the authors have reevaluated evidence presented in the favor of the latter model, with a discussion of phenotypic characteristics distinguishing normal resident microglia with those accumulating in HIV encephalitis (HIVE). CD163 is normally expressed by perivascular MPhi s but not resident microglia in normal CNS of humans and rhesus macaques. In agreement with other studies, the authors demonstrate expression of CD163 by brain MPhi s in HIVE and simian immunodeficiency virus encephalitis (SIVE). CNS tissues from HIV-sero positive individuals with HIVE or HIV-associated progressive multifocal leukoencephalopathy (PML) were also examined. In HIVE, the authors further demonstrate colocalization of CD163 and CD16 (Fcgamma III recptor) gene expression, the latter marker associated with HIV infection of monocyte in vivo and permissivity of infection. Indeed, CD163(+) MPhis and microglia are often productively infected in HIVE CNS. In SIV infected rhesus macaques, CD163(+) cells accumulate perivascularly, within nodular lesions and the parenchyma in animals with encephalitis. Likewise, parenchymal microglia and perivascular MPhi s are CD163(+) in HIVE. In contrast to HIVE, CD163(+)perivascular and parenchymal MPhi s in HIV-associated PML were only associated with areas of demyelinating lesions. Interestingly, SIV-infected rhesus macaques whose viral burden was predominantly at 1 x 10(6) copies/ml or greater developed encephalitis. To further investigate the relationship between CD163(+)/CD16(+) MPhis/microglia in the CNS and altered homeostasis in the periphery, the authors performed flow-cytometric analyses of peripheral blood mononuclear cells (PBMCs) from SIV-infected rhesus macaques. The results demonstrate an increase in the percent frequency of CD163(+)/CD16(+) monocytes in animals with detectable virus that correlated significantly with increased viral burden and CD4(+) T-cell decline. These results suggest the importance of this monocyte subset in HIV/SIV CNS disease, and also in the immune pathogenesis of lentiviral infection. The authors further discuss the potential role of CD163(+)/CD16(+) monocyte/MPhi subset expansion, altered myeloid homeostasis, and potential consequences for immune polarization and suppression. The results and discussion here suggest new avenues for the development of acquired immunodeficiency syndrome (AIDS) therapeutics and vaccine design.

Japanese encephalitis virus replication is negatively regulated by autophagy and occurs on LC3-I- and EDEM1-containing membranes.

PubMed

Sharma, Manish; Bhattacharyya, Sankar; Nain, Minu; Kaur, Manpreet; Sood, Vikas; Gupta, Vishal; Khasa, Renu; Abdin, Malik Z; Vrati, Sudhanshu; Kalia, Manjula

2014-09-01

Autophagy is a lysosomal degradative pathway that has diverse physiological functions and plays crucial roles in several viral infections. Here we examine the role of autophagy in the life cycle of JEV, a neurotropic flavivirus. JEV infection leads to induction of autophagy in several cell types. JEV replication was significantly enhanced in neuronal cells where autophagy was rendered dysfunctional by ATG7 depletion, and in Atg5-deficient mouse embryonic fibroblasts (MEFs), resulting in higher viral titers. Autophagy was functional during early stages of infection however it becomes dysfunctional as infection progressed resulting in accumulation of misfolded proteins. Autophagy-deficient cells were highly susceptible to virus-induced cell death. We also observed JEV replication complexes that are marked by nonstructural protein 1 (NS1) and dsRNA colocalized with endogenous LC3 but not with GFP-LC3. Colocalization of NS1 and LC3 was also observed in Atg5 deficient MEFs, which contain only the nonlipidated form of LC3. Viral replication complexes furthermore show association with a marker of the ER-associated degradation (ERAD) pathway, EDEM1 (ER degradation enhancer, mannosidase α-like 1). Our data suggest that virus replication occurs on ERAD-derived EDEM1 and LC3-I-positive structures referred to as EDEMosomes. While silencing of ERAD regulators EDEM1 and SEL1L suppressed JEV replication, LC3 depletion exerted a profound inhibition with significantly reduced RNA levels and virus titers. Our study suggests that while autophagy is primarily antiviral for JEV and might have implications for disease progression and pathogenesis of JEV, nonlipidated LC3 plays an important autophagy independent function in the virus life cycle.

A single tube PCR assay for simultaneous amplification of HSV-1/-2, VZV, CMV, HHV-6A/-6B, and EBV DNAs in cerebrospinal fluid from patients with virus-related neurological diseases.

PubMed

Yamamoto, T; Nakamura, Y

2000-10-01

Cerebrospinal fluid (CSF) specimens from 27 patients with encephalitis, meningitis, and other neurological diseases were studied for the presence of herpes simplex virus types 1 and 2 (HSV-1/-2), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesviruses 6A and 6B (HHV-6A/-6B) and Epstein-Barr virus (EBV) DNA using the polymerase chain reaction (PCR) method. The DNAs were amplified using two sets of consensus primer pairs in a single tube, bringing simultaneous amplification of the herpesviruses. The PCR products were analyzed by agarose gel electrophoresis, and Southern blot hybridization with virus-type specific probes, thus allowing discrimination between the different types of herpesviruses to be made. Each virus-specific probe was highly specific for identifying the PCR product. Thirty CSF specimens from 13 patients with encephalitis and 10 specimens from 10 patients with meningitis, respectively, were examined using this method. Eight patients with encephalitis and six with meningitis were positive for different herpesviruses, including patients with coinfections (HSV-1/-2 and VZV, VZV and CMV). Among four CSF specimens from four patients with other neurological disorders, dual amplification of CMV and EBV was present. Since identification of the types of herpesviruses in this system requires a very small amount of CSF, and is completed with one PCR, it is useful for routine diagnosis of herpesvirus infections in diagnostic laboratories. The viruses responsible for central nervous system infection are easily detected with various coinfection and serial patterns of herpesviruses, by this consensus primer-based PCR method. This may give an insight into the relationship between virus-related neurological diseases (VRNDS) and herpesvirus infections.

The impact of eastern equine encephalitis virus on efforts to recover the endangered whooping crane

USGS Publications Warehouse

Carpenter, J.W.; Clark, G.G.; Watts, D.M.; Cooper, J.E.

1989-01-01

The whooping crane (Grus americana), although never abundant in North America, became endangered primarily because of habitat modification and destruction. To help recovery, a captive propagation and reintroduction program was initiated at the Patuxent Wildlife Research Center (PWRC) in 1966. However, in 1984, 7 of 39 whooping cranes at PWRC died from infection by eastern equine encephalitis (EEE) virus, an arbovirus that infects a wide variety of indigenous bird species, although mortality is generally restricted to introduced birds. Following identification of the aetiological agent, surveillance and control measures were implemented, including serological monitoring of both wild and captive birds for EEE viral antibody and assay of locally-trapped mosquitoes for virus. In addition, an inactivated EEE virus vaccine developed for use in humans was evaluated in captive whooping cranes. Results so far suggest that the vaccine will afford protection to susceptible birds.

Interferon production by cells infected with subacute sclerosing panencephalitis (SSPE) virus or measles virus.

PubMed

Hasegawa, Shunji; Mori, Natsumi; Satomi, Mika; Jiang, Da-Peng; Hotta, Hak; Matsushige, Takeshi; Ichiyama, Takashi

2011-12-01

Subacute sclerosing panencephalitis (SSPE) is a rare progressive neurodegenerative encephalitis caused by some variants of measles virus (MV). The structure of SSPE virus in the brains of SSPE patients is different from that of MV. The difference in interferon (IFN) production between cells infected with SSPE virus and those infected with MV remains unclear. We measured the concentrations of IFN-α, β, γ, and λ1 (interleukin (IL)-29) from MV- or SSPE virus-infected B95a cells (a marmoset B-lymphoblastoid cell line). SSPE virus-infected B95a cells produced significantly higher levels of IFN-α and λ1 than did MV-infected or mock-infected cells. Our results suggest that SSPE virus and MV induce different IFN production profiles. Copyright © 2011 Elsevier Ltd. All rights reserved.

A glance at subgenomic flavivirus RNAs and microRNAs in flavivirus infections.

PubMed

Bavia, Lorena; Mosimann, Ana Luiza Pamplona; Aoki, Mateus Nóbrega; Duarte Dos Santos, Claudia Nunes

2016-05-28

The family Flaviviridae comprises a wide variety of viruses that are distributed worldwide, some of which are associated with high rates of morbidity and mortality. There are neither vaccines nor antivirals for most flavivirus infections, reinforcing the importance of research on different aspects of the viral life cycle. During infection, cytoplasmic accumulation of RNA fragments mainly originating from the 3' UTRs, which have been designated subgenomic flavivirus RNAs (sfRNAs), has been detected. It has been shown that eukaryotic exoribonucleases are involved in viral sfRNA production. Additionally, viral and human small RNAs (sRNAs) have also been found in flavivirus-infected cells, especially microRNAs (miRNAs). miRNAs were first described in eukaryotic cells and in a mature and functional state present as single-stranded 18-24 nt RNA fragments. Their main function is the repression of translation through base pairing with cellular mRNAs, besides other functions, such as mRNA degradation. Canonical miRNA biogenesis involves Drosha and Dicer, however miRNA can also be generated by alternative pathways. In the case of flaviviruses, alternative pathways have been suggested. Both sfRNAs and miRNAs are involved in viral infection and host cell response modulation, representing interesting targets of antiviral strategies. In this review, we focus on the generation and function of viral sfRNAs, sRNAs and miRNAs in West Nile, dengue, Japanese encephalitis, Murray Valley encephalitis and yellow fever infections, as well as their roles in viral replication, translation and cell immune response evasion. We also give an overview regarding other flaviviruses and the generation of cellular miRNAs during infection.

[Interaction of the Siberian and Far Eastern subtypes of tick-borne encephalitis virus in mammals with mixed infection. Competition of the subtypes in acute and inapparent infection].

PubMed

Gerasimov, S G; Pogodina, V V; Koliasnikova, N M; Karan', L S; Malenko, G V; Levina, L S

2011-01-01

Long-term monitoring of natural tick-borne encephalitis virus (TBEV) populations could reveal the change of TBEV subtypes, the displacement of the Far Eastern (FE) subtype, and its substitution for the Siberian (Sib) subtype. Acute and inapparent mixed infections were studied in Syrian hamsters to understand this phenomenon. The animals were inoculated with the Sib subtype and then with the FE one of TBEV (JQ845440-YaroslavI-Aver-08 and Fj214132-Kemerovo-Phateev-1954 strains). The inapparent form developed more frequently in mixed infection. Viral progeny was genotyped by reverse transcription polymerase chain reaction and hybridization fluorescence detection using genotype-specific probes. Independent reproduction of strains in the brain gave way to competition. The FE subtype dominated in hamster youngsters with acute infection. The Sib subtype had selective benefits in asymptomatic infection (adult hamsters infected intracerebrally and subcutaneously and youngsters infected subcutaneously). The competition of the subtypes was imperfect.

TC-83 vaccine protects against airborne or subcutaneous challenge with heterologous mouse-virulent strains of Venezuelan equine encephalitis virus.

PubMed

Phillpotts, R J; Wright, A J

1999-02-26

Vaccination with TC-83 virus produced solid protection against subcutaneous challenge with Venezuelan equine encephalitis (VEEV) viruses from homologous and heterologous serogroups, but breakthrough infection and disease occurred after airborne challenge. Breakthrough occurred more often with time after vaccination, and was more frequent with epizootic, homologous serogroup 1A/B viruses than with enzootic, heterologous serogroup viruses. A decrease in VEEV-specific IgA levels in the respiratory tract of vaccinated mice may explain the increased frequency of breakthrough with time after vaccination. However increased breakthrough with the highly virulent homologous serogroup 1A/B viruses (compared to less virulent viruses from heterologous serogroups) may be a consequence of their greater ability to invade the brain via the olfactory neuroepithelium and olfactory nerve.

West Nile Virus and Other Nationally Notifiable Arboviral Diseases - United States, 2016.

PubMed

Burakoff, Alexis; Lehman, Jennifer; Fischer, Marc; Staples, J Erin; Lindsey, Nicole P

2018-01-12

Arthropod-borne viruses (arboviruses) are transmitted to humans primarily through the bites of infected mosquitoes and ticks. West Nile virus (WNV) is the leading cause of domestically acquired arboviral disease in the continental United States (1,2). Other arboviruses, including La Crosse, Powassan, Jamestown Canyon, St. Louis encephalitis, and eastern equine encephalitis viruses, cause sporadic cases of disease and occasional outbreaks. This report summarizes surveillance data reported to CDC for 2016 for nationally notifiable arboviruses. It excludes dengue, chikungunya, and Zika viruses, as these are primarily nondomestic viruses typically acquired through travel. Forty-seven states and the District of Columbia (DC) reported 2,240 cases of domestic arboviral disease, including 2,150 (96%) WNV disease cases. Of the WNV disease cases, 1,310 (61%) were classified as neuroinvasive disease (e.g., meningitis, encephalitis, acute flaccid paralysis), for a national incidence of 0.41 cases per 100,000 population. After WNV, the most frequently reported arboviruses were La Crosse (35 cases), Powassan (22), and Jamestown Canyon (15) viruses. Because arboviral diseases continue to cause serious illness, maintaining surveillance is important to direct prevention activities.

Establishment of a panel of in-house polyclonal antibodies for the diagnosis of enterovirus infections.

PubMed

Kotani, Osamu; Iwata-Yoshikawa, Naoko; Suzuki, Tadaki; Sato, Yuko; Nakajima, Noriko; Koike, Satoshi; Iwasaki, Takuya; Sata, Tetsutaro; Yamashita, Teruo; Minagawa, Hiroko; Taguchi, Fumihiro; Hasegawa, Hideki; Shimizu, Hiroyuki; Nagata, Noriyo

2015-04-01

The aim of this study was to establish a reliable method of virus detection for the diagnosis of critical enterovirus infections such as acute infective encephalitis, encephalomyelitis and myocarditis. Because histopathological and immunohistochemical analyses of paraffin-embedded tissues play an important role in recognizing infectious agents in tissue samples, six in-house polyclonal antibodies raised against three representative enteroviruses using an indirect immunofluorescence assay and immunohistochemistry were examined. This panel of polyclonal antibodies recognized three serotypes of enterovirus. Two of the polyclonal antibodies were raised against denatured virus particles from enterovirus A71, one was raised against the recombinant VP1 protein of coxsackievirus B3, and the other for poliovirus type 1 were raised against denatured virus particles, the recombinant VP1 protein and peptide 2C. Western blot analysis revealed that each of these antibodies recognized the corresponding viral antigen and none cross-reacted with non-enteroviruses within the family Picornaviridae. However, all cross-reacted to some extent with the antigens derived from other serotypes of enterovirus. Indirect immunofluorescence assay and immunohistochemistry revealed that the virus capsid and non-structural proteins were localized in the cytoplasm of affected culture cells, and skeletal muscles and neurons in neonatal mice experimentally-infected with human enterovirus. The antibodies also recognized antigens derived from recent clinical isolates of enterovirus A71, coxsackievirus B3 and poliovirus. In addition, immunohistochemistry revealed that representative antibodies tested showed the same recognition pattern according to each serotype. Thus, the panel of in-house anti-enterovirus polyclonal antibodies described herein will be an important tool for the screening and pathological diagnosis for enterovirus infections, and may be useful for the classification of different enterovirus serotypes, including coxsackieviruses A and B, echoviruses, enterovirus A71 and poliovirus. © 2014 Japanese Society of Neuropathology.

Atypical presentation of West Nile virus in a newly diagnosed human immunodeficiency virus patient in New York City.

PubMed

Josekutty, Joby; Yeh, Richard; Mathew, Sheena; Ene, Ada; Ramessar, Nina; Trinidad, Jennilee

2013-04-01

Central nervous system manifestations of West Nile virus (WNV) infection include meningitis, encephalitis, and poliomyelitis-like syndrome. We describe a 44-year-old man with no past medical history who presented with a meningoencephalitic syndrome and spastic paralysis bilaterally in the upper and lower extremities, hyperreflexia, and myoclonus and was ultimately diagnosed as being infected with HIV and WNV.

Rift valley Fever virus encephalitis is associated with an ineffective systemic immune response and activated T cell infiltration into the CNS in an immunocompetent mouse model.

PubMed

Dodd, Kimberly A; McElroy, Anita K; Jones, Tara L; Zaki, Sherif R; Nichol, Stuart T; Spiropoulou, Christina F

2014-06-01

Rift Valley fever virus (RVFV) causes outbreaks of severe disease in livestock and humans throughout Africa and the Arabian Peninsula. In people, RVFV generally causes a self-limiting febrile illness but in a subset of individuals, it progresses to more serious disease. One manifestation is a delayed-onset encephalitis that can be fatal or leave the afflicted with long-term neurologic sequelae. In order to design targeted interventions, the basic pathogenesis of RVFV encephalitis must be better understood. To characterize the host immune responses and viral kinetics associated with fatal and nonfatal infections, mice were infected with an attenuated RVFV lacking NSs (ΔNSs) that causes lethal disease only when administered intranasally (IN). Following IN infection, C57BL/6 mice developed severe neurologic disease and succumbed 7-9 days post-infection. In contrast, inoculation of ΔNSs virus subcutaneously in the footpad (FP) resulted in a subclinical infection characterized by a robust immune response with rapid antibody production and strong T cell responses. IN-inoculated mice had delayed antibody responses and failed to clear virus from the periphery. Severe neurological signs and obtundation characterized end stage-disease in IN-inoculated mice, and within the CNS, the development of peak virus RNA loads coincided with strong proinflammatory responses and infiltration of activated T cells. Interestingly, depletion of T cells did not significantly alter survival, suggesting that neurologic disease is not a by-product of an aberrant immune response. Comparison of fatal (IN-inoculated) and nonfatal (FP-inoculated) ΔNSs RVFV infections in the mouse model highlighted the role of the host immune response in controlling viral replication and therefore determining clinical outcome. There was no evidence to suggest that neurologic disease is immune-mediated in RVFV infection. These results provide important insights for the future design of vaccines and therapeutic options.

Immunogenicity of a Japanese encephalitis chimeric virus vaccine as a booster dose after primary vaccination with SA14-14-2 vaccine in Thai children.

PubMed

Janewongwirot, Pakpoom; Puthanakit, Thanyawee; Anugulruengkitt, Suvaporn; Jantarabenjakul, Watsamon; Phasomsap, Chayapa; Chumket, Sompong; Yoksan, Sutee; Pancharoen, Chitsanu

2016-10-17

Japanese Encephalitis chimeric virus vaccine (JE-CV) and SA14-14-2 vaccine are live-attenuated JE vaccines produced from the same virus strain. Data on interchangeability is limited. To evaluate the immunogenicity and safety of JE-CV booster after primary vaccination with SA14-14-2 vaccine. This study was an open-label clinical trial in Thai children who had received a primary SA14-14-2 vaccination at 12-24monthsbefore enrollment (ClinicalTrials.gov NCT02602652). JE-CV was administered. A 50% plaque reduction neutralization test (PRNT 50 ) against three virus strains; JE-CV, SA-14-14-2andwild-type JE virus was measured before and 28-days post vaccination. The laboratory was performed at PRNT 50 titers ⩾10 (1/dil) were considered seroprotective against JE. Geometric mean titer (GMT) of PRNT 50 was calculated. Adverse events were observed for 28days. From March 2014 to June 2015, 50 children (64% male) were enrolled. Mean age and duration after primary vaccination was 26.9 (SD 4.6) and 12.8 (SD 2.7) months, respectively. The proportion of participants who had PRNT 50 pre and post-booster vaccination were 92% and 96% against JE-CV virus, 56% and 98% against SA-14-14-2 strain and 70% and 98% against wild-type JE virus, respectively. Solicited injection site reactions including erythema, pain and swelling occurred in 18%, 10% and 4% of subjects, respectively. Four children (8%) had fever (⩾37.7Celsius). Eight children (16%) had adverse events, which were not related to the vaccine. AJE-CV booster dose is highly immunogenic and safe among children who previously received SA14-14-2 vaccine. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Type I Interferon Response Determines Differences in Choroid Plexus Susceptibility between Newborns and Adults in Herpes Simplex Virus Encephalitis.

PubMed

Wilcox, Douglas R; Folmsbee, Stephen S; Muller, William J; Longnecker, Richard

2016-04-12

Newborns are significantly more susceptible to severe viral encephalitis than adults, with differences in the host response to infection implicated as a major factor. However, the specific host signaling pathways responsible for differences in susceptibility and neurologic morbidity have remained unknown. In a murine model of HSV encephalitis, we demonstrated that the choroid plexus (CP) is susceptible to herpes simplex virus 1 (HSV-1) early in infection of the newborn but not the adult brain. We confirmed susceptibility of the CP to HSV infection in a human case of newborn HSV encephalitis. We investigated components of the type I interferon (IFN) response in the murine brain that might account for differences in cell susceptibility and found that newborns have a dampened interferon response and significantly lower basal levels of the alpha/beta interferon (IFN-α/β) receptor (IFNAR) than do adults. To test the contribution of IFNAR to restricting infection from the CP, we infected IFNAR knockout (KO) adult mice, which showed restored CP susceptibility to HSV-1 infection in the adult. Furthermore, reduced IFNAR levels did not account for differences we found in the basal levels of several other innate signaling proteins in the wild-type newborn and the adult, including protein kinase R (PKR), that suggested specific regulation of innate immunity in the developing brain. Viral targeting of the CP, a region of the brain that plays a critical role in neurodevelopment, provides a link between newborn susceptibility to HSV and long-term neurologic morbidity among survivors of newborn HSV encephalitis. Compared to adults, newborns are significantly more susceptible to severe disease following HSV infection. Over half of newborn HSV infections result in disseminated disease or encephalitis, with long-term neurologic morbidity in 2/3 of encephalitis survivors. We investigated differences in host cell susceptibility between newborns and adults that contribute to severe central nervous system disease in the newborn. We found that, unlike the adult brain, the newborn choroid plexus (CP) was susceptible early in HSV-1 infection. We demonstrated that IFN-α/β receptor levels are lower in the newborn brain than in the adult brain and that deletion of this receptor restores susceptibility of the CP in the adult brain. The CP serves as a barrier between the blood and the cerebrospinal fluid and plays a role in proper neurodevelopment. Susceptibility of the newborn choroid plexus to HSV-1 has important implications in viral spread to the brain and, also, in the neurologic morbidity following HSV encephalitis. Copyright © 2016 Wilcox et al.

Quantitative autoradiographic mapping of herpes simplex virus encephalitis with a radiolabeled antiviral drug

DOE Office of Scientific and Technical Information (OSTI.GOV)

Saito, Y.; Price, R.W.; Rottenberg, D.A.

1982-09-17

2'-Fluoro-5-methyl-1-..beta..-D-arabinosyluracil (FMAU) labeled with carbon-14 was used to image herpes simplex virus type 1-infected regions of rat brain by quantitative autoradiography. FMAU is a potent antiviral pyrimidine nucleoside which is selectively phosphorylated by virus-coded thymidine kinase. When the labeled FMAU was administered 6 hours before the rats were killed, the selective uptake and concentration of the drug and its metabolites by infected cells (defined by immunoperoxidase staining of viral antigens) allowed quantitative definition and mapping of HSV-1-infected structures in autoradiograms of brain sections. These results shown that quantitative autoradiography can be used to characterize the local metabolism of antiviral drugsmore » by infected cells in vivo. They also suggest that the selective uptake of drugs that exploit viral thymidine kinase for their antiviral effect can, by appropriate labeling, be used in conjunction with clinical neuroimaging techniques to define infected regions of human brain, thereby providing a new approach to the diagnosis of herpes encephalitis in man.« less

Pharmacokinetics of the Antiviral Lectin Griffithsin Administered by Different Routes Indicates Multiple Potential Uses.

PubMed

Barton, Christopher; Kouokam, J Calvin; Hurst, Harrell; Palmer, Kenneth E

2016-12-17

Griffithsin (GRFT) is a red alga-derived lectin with demonstrated broad spectrum antiviral activity against enveloped viruses, including severe acute respiratory syndrome-Coronavirus (SARS-CoV), Japanese encephalitis virus (JEV), hepatitis C virus (HCV), and herpes simplex virus-2 (HSV-2). However, its pharmacokinetic profile remains largely undefined. Here, Sprague Dawley rats were administered a single dose of GRFT at 10 or 20 mg/kg by intravenous, oral, and subcutaneous routes, respectively, and serum GRFT levels were measured at select time points. In addition, the potential for systemic accumulation after oral dosing was assessed in rats after 10 daily treatments with GRFT (20 or 40 mg/kg). We found that parenterally-administered GRFT in rats displayed a complex elimination profile, which varied according to administration routes. However, GRFT was not orally bioavailable, even after chronic treatment. Nonetheless, active GRFT capable of neutralizing HIV-Env pseudoviruses was detected in rat fecal extracts after chronic oral dosing. These findings support further evaluation of GRFT for pre-exposure prophylaxis against emerging epidemics for which specific therapeutics are not available, including systemic and enteric infections caused by susceptible enveloped viruses. In addition, GRFT should be considered for antiviral therapy and the prevention of rectal transmission of HIV-1 and other susceptible viruses.

A Cluster of Fatal Tick-borne Encephalitis Virus Infection in Organ Transplant Setting.

PubMed

Lipowski, Dariusz; Popiel, Marta; Perlejewski, Karol; Nakamura, Shota; Bukowska-Osko, Iwona; Rzadkiewicz, Ewa; Dzieciatkowski, Tomasz; Milecka, Anna; Wenski, Wojciech; Ciszek, Michal; Debska-Slizien, Alicja; Ignacak, Ewa; Cortes, Kamila Caraballo; Pawelczyk, Agnieszka; Horban, Andrzej; Radkowski, Marek; Laskus, Tomasz

2017-03-15

Tick-borne encephalitis virus (TBEV) infection has become a major health problem in Europe and is currently a common cause of viral brain infection in many countries. Encephalitis in transplant recipients, althrough rare, is becoming a recognized complication. Our study provides the first description of transmission of TBEV through transplantation of solid organs. Three patients who received solid organ transplants from a single donor (2 received kidney, and 1 received liver) developed encephalitis 17-49 days after transplantation and subsequently died. Blood and autopsy tissue samples were tested by next-generation sequencing (NGS) and reverse transcription polymerase chain reaction (RT-PCR). All 3 recipients were first analyzed in autopsy brain tissue samples and/or cerebrospinal fluid by NGS, which yielded 24-52 million sequences per sample and 9-988 matched TBEV sequences in each patient. The presence of TBEV was confirmed by RT-PCR in all recipients and in the donor, and direct sequencing of amplification products corroborated the presence of the same viral strain. We demonstrated transmission of TBEV by transplantation of solid organs. In such a setting, TBEV infection may be fatal, probably due to pharmacological immunosuppression. Organ donors should be screened for TBEV when coming from or visiting endemic areas. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

USSR Report, Life Sciences Biomedical and Behavioral Sciences.

DTIC Science & Technology

1984-03-14

demonstrated that infection with tick-borne encephalitis (TBE) virus or Langat virus leads to the appearance of two populations of autoreactive T...cells formed in mice ^fected wiA the TBE or Langat viruses exert a protective effect by preventing the maturation of the ACTL precursor cells Into

Expanding possibilities for intervention against small ruminant lentiviruses through genetic marker-assisted selective breeding

USDA-ARS?s Scientific Manuscript database

Small ruminant lentiviruses include members that infect sheep (ovine lentivirus [OvLV]; also known as ovine progressive pneumonia virus/maedi-visna virus) and goats (caprine arthritis encephalitis virus [CAEV]). Breed differences in seroprevalence and proviral concentration of OvLV had suggested a s...

A conserved predicted pseudoknot in the NS2A-encoding sequence of West Nile and Japanese encephalitis flaviviruses suggests NS1' may derive from ribosomal frameshifting

PubMed Central

Firth, Andrew E; Atkins, John F

2009-01-01

Japanese encephalitis, West Nile, Usutu and Murray Valley encephalitis viruses form a tight subgroup within the larger Flavivirus genus. These viruses utilize a single-polyprotein expression strategy, resulting in ~10 mature proteins. Plotting the conservation at synonymous sites along the polyprotein coding sequence reveals strong conservation peaks at the very 5' end of the coding sequence, and also at the 5' end of the sequence encoding the NS2A protein. Such peaks are generally indicative of functionally important non-coding sequence elements. The second peak corresponds to a predicted stable pseudoknot structure whose biological importance is supported by compensatory mutations that preserve the structure. The pseudoknot is preceded by a conserved slippery heptanucleotide (Y CCU UUU), thus forming a classical stimulatory motif for -1 ribosomal frameshifting. We hypothesize, therefore, that the functional importance of the pseudoknot is to stimulate a portion of ribosomes to shift -1 nt into a short (45 codon), conserved, overlapping open reading frame, termed foo. Since cleavage at the NS1-NS2A boundary is known to require synthesis of NS2A in cis, the resulting transframe fusion protein is predicted to be NS1-NS2AN-term-FOO. We hypothesize that this may explain the origin of the previously identified NS1 'extension' protein in JEV-group flaviviruses, known as NS1'. PMID:19196463

The dominant roles of ICAM-1-encoding gene in DNA vaccination against Japanese encephalitis virus are the activation of dendritic cells and enhancement of cellular immunity.

PubMed

Zhai, Yong-Zhen; Zhou, Yan; Ma, Li; Feng, Guo-He

2013-01-01

We investigated the cellular immune responses elicited by a plasmid DNA vaccine encoding prM-E protein from the Japanese encephalitis (JE) virus (JEV) with or without various forms of intercellular adhesion molecule (ICAM)-1 gene to maximize the immune responses evoked by the JE DNA vaccine. We observed that co-immunization with the construct containing murine ICAM-1 gene (pICAM-1) resulted in a significant increase in the percentage of CD4(+)T cells, high level of JEV-specific cytotoxic T lymphocyte response, and high production of T helper 1 (Th1)-type cytokines in splenic T cells. Furthermore, the co-expression of ICAM-1 and DNA immunogens was found to be more effective in generating T cell-mediated immune responses than those induced by immunization with pJME in combination with pICAM-1. Our results suggested that ICAM-1 enhanced T cell receptor signaling and activated Th1 immune responses in the JEV model system by increasing the induction of CD4(+)Th1 cell subset and activating dendritic cells. Copyright © 2013 Elsevier Inc. All rights reserved.

Detection of West Nile virus and tick-borne encephalitis virus in birds in Slovakia, using a universal primer set.

PubMed

Csank, Tomáš; Bhide, Katarína; Bencúrová, Elena; Dolinská, Saskia; Drzewnioková, Petra; Major, Peter; Korytár, Ľuboš; Bocková, Eva; Bhide, Mangesh; Pistl, Juraj

2016-06-01

West Nile virus (WNV) is a mosquito-borne neurotropic pathogen that presents a major public health concern. Information on WNV prevalence and circulation in Slovakia is insufficient. Oral and cloacal swabs and bird brain samples were tested for flavivirus RNA by RT-PCR using newly designed generic primers. The species designation was confirmed by sequencing. WNV was detected in swab and brain samples, whereas one brain sample was positive for tick-borne encephalitis virus (TBEV). The WNV sequences clustered with lineages 1 and 2. These results confirm the circulation of WNV in birds in Slovakia and emphasize the risk of infection of humans and horses.

Complete inactivation of Venezuelan equine encephalitis virus by 1,5-iodonaphthylazide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sharma, Anuj; Birla Institute of Technology and Science, Pilani; Raviv, Yossef

2007-06-29

Hydrophobic alkylating compounds like 1,5-iodonaphthylazide (INA) partitions into biological membranes and accumulates selectively into the hydrophobic domain of the lipid bilayer. Upon irradiation with far UV light, INA binds selectively to transmembrane proteins in the viral envelope and renders them inactive. Such inactivation does not alter the ectodomains of the membrane proteins thus preserving the structural and conformational integrity of immunogens on the surface of the virus. In this study, we have used INA to inactivate Venezuelan equine encephalitis virus (VEEV). Treatment of VEEV with INA followed by irradiation with UV light resulted in complete inactivation of the virus. Immuno-fluorescencemore » for VEEV and virus titration showed no virus replication in-vitro. Complete loss of infectivity was also achieved in mice infected with INA treated plus irradiated preparations of VEEV. No change in the structural integrity of VEEV particles were observed after treatment with INA plus irradiation as assessed by electron microscopy. This data suggest that such inactivation strategies can be used for developing vaccine candidates for VEEV and other enveloped viruses.« less

RNA viruses can hijack vertebrate microRNAs to suppress innate immunity

NASA Astrophysics Data System (ADS)

Trobaugh, Derek W.; Gardner, Christina L.; Sun, Chengqun; Haddow, Andrew D.; Wang, Eryu; Chapnik, Elik; Mildner, Alexander; Weaver, Scott C.; Ryman, Kate D.; Klimstra, William B.

2014-02-01

Currently, there is little evidence for a notable role of the vertebrate microRNA (miRNA) system in the pathogenesis of RNA viruses. This is primarily attributed to the ease with which these viruses mutate to disrupt recognition and growth suppression by host miRNAs. Here we report that the haematopoietic-cell-specific miRNA miR-142-3p potently restricts the replication of the mosquito-borne North American eastern equine encephalitis virus in myeloid-lineage cells by binding to sites in the 3' non-translated region of its RNA genome. However, by limiting myeloid cell tropism and consequent innate immunity induction, this restriction directly promotes neurologic disease manifestations characteristic of eastern equine encephalitis virus infection in humans. Furthermore, the region containing the miR-142-3p binding sites is essential for efficient virus infection of mosquito vectors. We propose that RNA viruses can adapt to use antiviral properties of vertebrate miRNAs to limit replication in particular cell types and that this restriction can lead to exacerbation of disease severity.

A Protective Role for Interleukin-1 Signaling during Mouse Adenovirus Type 1-Induced Encephalitis.

PubMed

Castro-Jorge, Luiza A; Pretto, Carla D; Smith, Asa B; Foreman, Oded; Carnahan, Kelly E; Spindler, Katherine R

2017-02-15

Interleukin-1β (IL-1β), an inflammatory cytokine and IL-1 receptor ligand, has diverse activities in the brain. We examined whether IL-1 signaling contributes to the encephalitis observed in mouse adenovirus type 1 (MAV-1) infection, using mice lacking the IL-1 receptor (Il1r1 -/- mice). Il1r1 -/- mice demonstrated reduced survival, greater disruption of the blood-brain barrier (BBB), higher brain viral loads, and higher brain inflammatory cytokine and chemokine levels than control C57BL/6J mice. We also examined infections of mice defective in IL-1β production (Pycard -/- mice) and mice defective in trafficking of Toll-like receptors to the endosome (Unc93b1 -/- mice). Pycard -/- and Unc93b1 -/- mice showed lower survival (similar to Il1r1 -/- mice) than control mice but, unlike Il1r1 -/- mice, did not have increased brain viral loads or BBB disruption. Based on the brain cytokine levels, MAV-1-infected Unc93b1 -/- mice had a very different inflammatory profile from infected Il1r1 -/- and Pycard -/- mice. Histological examination demonstrated pathological findings consistent with encephalitis in control and knockout mice; however, intranuclear viral inclusions were seen only in Il1r1 -/- mice. A time course of infection of control and Il1r1 -/- mice evaluating the kinetics of viral replication and cytokine production revealed differences between the mouse strains primarily at 7 to 8 days after infection, when mice began succumbing to MAV-1 infection. In the absence of IL-1 signaling, we noted an increase in the transcription of type I interferon (IFN)-stimulated genes. Together, these results indicate that IL-1 signaling is important during MAV-1 infection and suggest that, in its absence, increased IFN-β signaling may result in increased neuroinflammation. The investigation of encephalitis pathogenesis produced by different viruses is needed to characterize virus and host-specific factors that contribute to disease. MAV-1 produces viral encephalitis in its natural host, providing a good model for studying factors involved in encephalitis development. We investigated the role of IL-1 signaling during MAV-1-induced encephalitis. Unexpectedly, the lack of IL-1 signaling increased the mortality and inflammation in mice infected with MAV-1. Also, there was an increase in the transcription of type I IFN-stimulated genes that correlated with the observed increased mortality and inflammation. The findings highlight the complex nature of encephalitis and suggests that IL-1 has a protective effect for the development of MAV-1-induced encephalitis. Copyright © 2017 American Society for Microbiology.

The outbreak of West Nile virus infection in the New York City area in 1999.

PubMed

Nash, D; Mostashari, F; Fine, A; Miller, J; O'Leary, D; Murray, K; Huang, A; Rosenberg, A; Greenberg, A; Sherman, M; Wong, S; Layton, M

2001-06-14

In late August 1999, an unusual cluster of cases of meningoencephalitis associated with muscle weakness was reported to the New York City Department of Health. The initial epidemiologic and environmental investigations suggested an arboviral cause. Active surveillance was implemented to identify patients hospitalized with viral encephalitis and meningitis. Cerebrospinal fluid, serum, and tissue specimens from patients with suspected cases underwent serologic and viral testing for evidence of arboviral infection. Outbreak surveillance identified 59 patients who were hospitalized with West Nile virus infection in the New York City area during August and September of 1999. The median age of these patients was 71 years (range, 5 to 95). The overall attack rate of clinical West Nile virus infection was at least 6.5 cases per million population, and it increased sharply with age. Most of the patients (63 percent) had clinical signs of encephalitis; seven patients died (12 percent). Muscle weakness was documented in 27 percent of the patients and flaccid paralysis in 10 percent; in all of the latter, nerve conduction studies indicated an axonal polyneuropathy in 14 percent. An age of 75 years or older was an independent risk factor for death (relative risk adjusted for the presence or absence of diabetes mellitus, 8.5; 95 percent confidence interval, 1.2 to 59.1), as was the presence of diabetes mellitus (age-adjusted relative risk, 5.1; 95 percent confidence interval, 1.5 to 17.3). This outbreak of West Nile meningoencephalitis in the New York City metropolitan area represents the first time this virus has been detected in the Western Hemisphere. Given the subsequent rapid spread of the virus, physicians along the eastern seaboard of the United States should consider West Nile virus infection in the differential diagnosis of encephalitis and viral meningitis during the summer months, especially in older patients and in those with muscle weakness.

Fatal Transplant-Associated West Nile Virus Encephalitis and Public Health Investigation—California, 2010

PubMed Central

Rabe, Ingrid B.; Schwartz, Brian S.; Farnon, Eileen C.; Josephson, S. Andrew; Webber, Allison B.; Roberts, John Paul; de Mattos, Angelo M.; Gallay, Brian J.; van Slyck, Sean; Messenger, Sharon L.; Yen, Cynthia J.; Bloch, Evan M.; Drew, Clifton P.; Fischer, Marc; Glaser, Carol A.

2017-01-01

Background In December 2010, a case of West Nile virus (WNV) encephalitis occurring in a kidney recipient shortly after organ transplantation was identified. Methods A public health investigation was initiated to determine the likely route of transmission, detect potential WNV infections among recipients from the same organ donor, and remove any potentially infected blood products or tissues. Available serum, cerebrospinal fluid, and urine samples from the organ donor and recipients were tested for WNV infection by nucleic acid testing and serology. Results Two additional recipients from the same organ donor were identified, their clinical and exposure histories were reviewed, and samples were obtained. WNV RNA was retrospectively detected in the organ donor’s serum. After transplantation, the left kidney recipient had serologic and molecular evidence of WNV infection and the right kidney recipient had prolonged but clinically inapparent WNV viremia. The liver recipient showed no clinical signs of infection but had flavivirus IgG antibodies; however, insufficient samples were available to determine the timing of infection. No remaining infectious products or tissues were identified. Conclusions Clinicians should suspect WNV as a cause of encephalitis in organ transplant recipients and report cases to public health departments for prompt investigation of the source of infection. Increased use of molecular testing and retaining pretransplantation sera may improve the ability to detect and diagnose transplant-associated WNV infection in organ transplant recipients. PMID:23823653

The pathogenesis of bornaviral diseases in mammals.

PubMed

Tizard, Ian; Ball, Judith; Stoica, George; Payne, Susan

2016-12-01

Natural bornavirus infections and their resulting diseases are largely restricted to horses and sheep in Central Europe. The disease also occurs naturally in cats, and can be induced experimentally in laboratory rodents and numerous other mammals. Borna disease virus-1 (BoDV-1), the cause of most cases of mammalian Borna disease, is a negative-stranded RNA virus that replicates within the nucleus of target cells. It causes severe, often lethal, encephalitis in susceptible species. Recent events, especially the discovery of numerous new species of bornaviruses in birds and a report of an acute, lethal bornaviral encephalitis in humans, apparently acquired from squirrels, have revived interest in this remarkable family of viruses. The clinical manifestations of the bornaviral diseases are highly variable. Thus, in addition to acute lethal encephalitis, they can cause persistent neurologic disease associated with diverse behavioral changes. They also cause a severe retinitis resulting in blindness. In this review, we discuss both the pathological lesions observed in mammalian bornaviral disease and the complex pathogenesis of the neurologic disease. Thus infected neurons may be destroyed by T-cell-mediated cytotoxicity. They may die as a result of excessive inflammatory cytokine release from microglia. They may also die as a result of a 'glutaminergic storm' due to a failure of infected astrocytes to regulate brain glutamate levels.

Genetic and Biological Characterization of Tick-Borne Encephalitis Virus Isolated from Wild Rodents in Southern Hokkaido, Japan in 2008

PubMed Central

Yamazaki, Shoko; Mottate, Keita; Nagata, Noriyo; Seto, Takahiro; Sanada, Takashiro; Sakai, Mizuki; Kariwa, Hiroaki; Takashima, Ikuo

2013-01-01

Abstract Tick-borne encephalitis virus (TBEV) is a zoonotic agent causing severe encephalitis in humans. A recent epizootiological survey indicated that endemic foci of TBEV have been maintained in the southern part of Hokkaido until recently. In this study, we sought to isolate TBEV from wild rodents in the area. One virus, designated Oshima 08-As, was isolated from an Apodemus speciosus captured in Hokuto in 2008. Oshima 08-As was classified as the Far Eastern subtype of TBEV and formed a cluster with the other strains isolated in Hokkaido from 1995 to 1996. Thirty-six nucleotide differences resulted in 12 amino acid changes between Oshima 08-As and Oshima 5–10 isolated in 1995. Oshima 08-As caused high mortality and morbidity in a mouse model compared with Oshima 5–10. Although similar transient viral multiplication in the spleen was observed in the mice infected with Oshima 08-As and Oshima 5–10, greater viral multiplication with an inflammatory response was noted in the brains of mice infected with Oshima 08-As than those infected with Oshima 5–10. These data indicate that a few naturally occurring mutations affect the pathogenicity of the Oshima strains endemic in the southern part of Hokkaido. PMID:23590320

A Broadly Flavivirus Cross-Neutralizing Monoclonal Antibody that Recognizes a Novel Epitope within the Fusion Loop of E Protein

PubMed Central

Jiang, Tao; Wang, Hua-Jing; Yang, Hai-ou; Tan, Weng-Long; Liu, Ran; Yu, Man; Ge, Bao-Xue; Zhu, Qing-Yu; Qin, E-De; Guo, Ya-Jun; Qin, Cheng-Feng

2011-01-01

Flaviviruses are a group of human pathogenic, enveloped RNA viruses that includes dengue (DENV), yellow fever (YFV), West Nile (WNV), and Japanese encephalitis (JEV) viruses. Cross-reactive antibodies against Flavivirus have been described, but most of them are generally weakly neutralizing. In this study, a novel monoclonal antibody, designated mAb 2A10G6, was determined to have broad cross-reactivity with DENV 1–4, YFV, WNV, JEV, and TBEV. Phage-display biopanning and structure modeling mapped 2A10G6 to a new epitope within the highly conserved flavivirus fusion loop peptide, the 98DRXW101 motif. Moreover, in vitro and in vivo experiments demonstrated that 2A10G6 potently neutralizes DENV 1–4, YFV, and WNV and confers protection from lethal challenge with DENV 1–4 and WNV in murine model. Furthermore, functional studies revealed that 2A10G6 blocks infection at a step after viral attachment. These results define a novel broadly flavivirus cross-reactive mAb with highly neutralizing activity that can be further developed as a therapeutic agent against severe flavivirus infections in humans. PMID:21264311

Correlation of Acute Humoral Response with Brain Virus Burden and Survival Time in Pig-Tailed Macaques Infected with the Neurovirulent Simian Immunodeficiency Virus SIVsmmFGb

PubMed Central

O’Neil, Shawn P.; Suwyn, Carolyn; Anderson, Daniel C.; Niedziela, Genevieve; Bradley, Juliette; Novembre, Francis J.; Herndon, James G.; McClure, Harold M.

2004-01-01

Infection of pig-tailed macaques with the simian immunodeficiency virus (SIV) isolate SIVsmmFGb frequently results in SIV encephalitis (SIVE) in addition to immunodeficiency and acquired immune deficiency syndrome. We used in situ hybridization to quantitate the number of SIV-infected cells in brain parenchyma, choroid plexus, and meninges from 17 macaques that developed acquired immune deficiency syndrome after infection with SIVsmmFGb. SIV-infected cells and histopathological lesions of SIVE were identified in 15 of 17 animals (88.2%), including 12 of 12 rapid progressors (RP) and 3 of 5 slow progressors (SP). The parenchymal virus burden was much greater in RP macaques than in the three SP macaques with SIVE (median values of 24.3 versus 0.3 infected cells/mm2, respectively; P < 0.05). Viral load differences between RP and SP with SIVE were less marked in choroid plexus (29.6 versus 12.8 infected cells/mm2, respectively) and meninges (133.0 versus 34.2 infected cells/mm2, respectively). A significant negative correlation was observed between the magnitude of the anti-SIV antibody titer at 1 month after inoculation and brain virus burden at necropsy (r = −0.614; P < 0.01). The close association between immune response and SIVE in this model should prove useful for identifying correlates of immune protection against primate lentiviral encephalitis. PMID:15039205

High costs of infection: Alphavirus infection reduces digestive function and bone and feather growth in nestling house sparrows (Passer domesticus).

PubMed

Fassbinder-Orth, Carol A; Killpack, Tess L; Goto, Dylan S; Rainwater, Ellecia L; Shearn-Bochsler, Valerie I

2018-01-01

Increasingly, ecoimmunology studies aim to use relevant pathogen exposure to examine the impacts of infection on physiological processes in wild animals. Alphaviruses are arthropod-borne, single-stranded RNA (ssRNA) viruses ("arboviruses") responsible for millions of cases of human illnesses each year. Buggy Creek virus (BCRV) is a unique alphavirus that is transmitted by a cimicid insect, the swallow bug, and is amplified in two avian species: the house sparrow (Passer domesticus) and the cliff swallow (Petrochelidon pyrrhonota). BCRV, like many alphaviruses, exhibits age-dependent susceptibility where the young are most susceptible to developing disease and exhibit a high mortality rate. However, alphavirus disease etiology in nestling birds is unknown. In this study, we infected nestling house sparrows with Buggy Creek virus and measured virological, pathological, growth, and digestive parameters following infection. Buggy Creek virus caused severe encephalitis in all infected nestlings, and the peak viral concentration in brain tissue was over 34 times greater than any other tissue. Growth, tissue development, and digestive function were all significantly impaired during BCRV infection. However, based on histopathological analysis performed, this impairment does not appear to be the result of direct tissue damage by the virus, but likely caused by encephalitis and neuronal invasion and impairment of the central nervous system. This is the first study to examine the course of alphavirus diseases in nestling birds and these results will improve our understanding of age-dependent infections of alphaviruses in vertebrate hosts.

High costs of infection: Alphavirus infection reduces digestive function and bone and feather growth in nestling house sparrows (Passer domesticus)

USGS Publications Warehouse

Fassbinder-Orth, Carol A.; Killpack, Tess L.; Goto, Dylan S.; Rainwater, Ellecia L.; Shearn-Bochsler, Valerie I.

2018-01-01

Increasingly, ecoimmunology studies aim to use relevant pathogen exposure to examine the impacts of infection on physiological processes in wild animals. Alphaviruses are arthropod-borne, single-stranded RNA (ssRNA) viruses (“arboviruses”) responsible for millions of cases of human illnesses each year. Buggy Creek virus (BCRV) is a unique alphavirus that is transmitted by a cimicid insect, the swallow bug, and is amplified in two avian species: the house sparrow (Passer domesticus) and the cliff swallow (Petrochelidon pyrrhonota). BCRV, like many alphaviruses, exhibits age-dependent susceptibility where the young are most susceptible to developing disease and exhibit a high mortality rate. However, alphavirus disease etiology in nestling birds is unknown. In this study, we infected nestling house sparrows with Buggy Creek virus and measured virological, pathological, growth, and digestive parameters following infection. Buggy Creek virus caused severe encephalitis in all infected nestlings, and the peak viral concentration in brain tissue was over 34 times greater than any other tissue. Growth, tissue development, and digestive function were all significantly impaired during BCRV infection. However, based on histopathological analysis performed, this impairment does not appear to be the result of direct tissue damage by the virus, but likely caused by encephalitis and neuronal invasion and impairment of the central nervous system. This is the first study to examine the course of alphavirus diseases in nestling birds and these results will improve our understanding of age-dependent infections of alphaviruses in vertebrate hosts.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meagher, Robert J.; Ball, Cameron Scott; Langevin, Stanley A.

In this study, collection of mosquitoes and testing for vector-borne viruses is a key surveillance activity that directly influences the vector control efforts of public health agencies, including determining when and where to apply insecticides. Vector control districts in California routinely monitor for three human pathogenic viruses including West Nile virus (WNV), Western equine encephalitis virus (WEEV), and St. Louis encephalitis virus (SLEV). Reverse transcription quantitative polymerase chain reaction (RT-qPCR) offers highly sensitive and specific detection of these three viruses in a single multiplex reaction, but this technique requires costly, specialized equipment that is generally only available in centralized publicmore » health laboratories. We report the use of reverse transcription loop-mediated isothermal amplification (RT-LAMP) to detect WNV, WEEV, and SLEV RNA extracted from pooled mosquito samples collected in California, including novel primer sets for specific detection of WEEV and SLEV, targeting the nonstructural protein 4 (nsP4) gene of WEEV and the 3’ untranslated region (3’-UTR) of SLEV. Our WEEV and SLEV RT-LAMP primers allowed detection of <0.1 PFU/reaction of their respective targets in <30 minutes, and exhibited high specificity without cross reactivity when tested against a panel of alphaviruses and flaviviruses. Furthermore, the SLEV primers do not cross-react with WNV, despite both viruses being closely related members of the Japanese encephalitis virus complex. The SLEV and WEEV primers can also be combined in a single RT-LAMP reaction, with discrimination between amplicons by melt curve analysis. Although RT-qPCR is approximately one order of magnitude more sensitive than RT-LAMP for all three targets, the RT-LAMP technique is less instrumentally intensive than RT-qPCR and provides a more cost-effective method of vector-borne virus surveillance.« less

[Characteristics of long-term persisting strains of tick-borne encephalitis virus in different forms of the chronic process in animals].

PubMed

Frolova, T V; Pogodina, V V; Frolova, M P; Karmysheva, V Ia

1982-01-01

The properties of the Vasilchenko strain of tick-borne encephalitis (TBE) virus and its 3 variants isolated at various stages of persistent infection (383, 453, and 535 days) in Macaca rhesus monkeys and Syrian hamsters with different forms of the chronic TBE were studied. The process characterized by chronic focal inflammatory-degenerative changes in the brains of hamsters without the disturbance of motor functions was associated with persistence of different kinds of virus-specific antigens without virulent virus production. Brain explants of this group of hamsters yielded a virus with cytopathogenic properties but not pathogenic for mice. In a chronic disease developing without the initial acute period, a virus was recovered from hamsters which proved to be virulent for mice and to possess the hemagglutinating and high invasive activity. The most virulent strain was isolated from monkeys with continuously progressive chronic encephalitis with steady paralysis of the extremities. This isolate differed from the parental Vasilchenko strain by a high pathogenicity for hamsters by intracerebral and subcutaneous routes, and thermostability at 50 degrees C.

West Nile Virus and Other Nationally Notifiable Arboviral Diseases - United States, 2015.

PubMed

Krow-Lucal, Elisabeth; Lindsey, Nicole P; Lehman, Jennifer; Fischer, Marc; Staples, J Erin

2017-01-20

Arthropod-borne viruses (arboviruses) are transmitted to humans primarily through the bites of infected mosquitoes and ticks. The leading cause of domestically acquired arboviral disease in the United States is West Nile virus (WNV) (1). Other arboviruses, including La Crosse, St. Louis encephalitis, Jamestown Canyon, Powassan, and eastern equine encephalitis viruses, also cause sporadic cases and outbreaks. This report summarizes surveillance data reported to CDC in 2015 for nationally notifiable arboviruses. It excludes dengue, chikungunya, and Zika viruses, which are primarily nondomestic viruses typically acquired through travel (and are addressed in other CDC reports). In 2015, 45 states and the District of Columbia (DC) reported 2,282 cases of domestic arboviral disease. Among these cases, 2,175 (95%) were WNV disease and 1,455 (67%) of those were classified as neuroinvasive disease (meningitis, encephalitis, or acute flaccid paralysis). The national incidence of WNV neuroinvasive disease was 0.45 cases per 100,000 population. Because arboviral diseases continue to cause serious illness, maintaining surveillance is important to direct prevention activities such as reduction of vector populations and screening of blood donors.

West Nile virus in livestock and wildlife

USGS Publications Warehouse

McLean, R.G.; Ubico, S.R.; Bourne, D.; Komar, N.

2002-01-01

WN virus is one of the most ubiquitous arboviruses occurring over a broad geographical range and in a wide diversity of vertebrate host and vector species. The virus appears to be maintained in endemic foci on the African continent and is transported annually to temperate climates to the north in Europe and to the south in South Africa. Reports of clinical disease due to natural WN virus infection in wild or domestic animals were much less common than reports of infection (virus isolation or antibody detection). Until recently, records of morbidity and mortality in wild birds were confined to a small number of cases and infections causing encephalitis, sometimes fatal, in horses were reported infrequently. In the period 1996-2001, there was an increase in outbreaks of illness due to WN virus in animals as well as humans. Within the traditional range of WN virus, encephalitis was reported in horses in Italy in 1998 and in France in 2000. The first report of disease and deaths caused by WN virus infection in domestic birds was reported in Israel in 1997-1999, involving hundreds of young geese. In 1999 WN virus reached North America and caused an outbreak of encephalitis in humans in the New York area at the same time as a number of cases of equine encephalitis and deaths in American crows and a variety of other bird species, both North American natives and exotics. Multi-state surveillance for WN virus has been in place since April 2000 and has resulted in the detection of WN virus in thousands of dead birds from an increasing number of species in North America, and also in several species of mammals. The surveillance system that has developed in North America because of the utility of testing dead birds for the rapid detection of WN virus presence has been a unique integration of public health and wildlife health agencies. It has been suggested that the recent upsurge in clinical WN virus infection in wild and domestic animals as well as in humans may be related to the emergence of one or more new strains of WN virus. Virus isolated in New York in 1999 was found to be identical to that from Israel. It was alarming for WN virus to so easily invade the United States and surprising that it became established so quickly in the temperature climate of New York. Its persistence and rapid expansion in the United States leave a number of unanswered questions. New disease characteristics and patterns have occurred and more are evolving as WN virus further invades the western hemisphere. Additional animal research is needed to answer these questions. Some of the research needs include bird migration as a mechanism of virus dispersal, vector and vertebrate host relationships, virus persistence mechanisms, laboratory diagnosis, viral pathogenesis, risk factor studies, vaccine development, and WN virus impact on wildlife (CDC 2001a). Determination of the primary reservoir host species that are involved in the epidemiology of WN virus and the suitable sentinel species for active surveillance are also important research areas.

Lentiviral infection of proliferating brain macrophages in HIV and simian immunodeficiency virus encephalitis despite sterile alpha motif and histidine-aspartate domain-containing protein 1 expression

PubMed Central

Lindgren, Allison A.; Filipowicz, Adam R.; Hattler, Julian B.; Kim, Soon Ok; Chung, Hye Kyung; Kuroda, Marcelo J.; Johnson, Edward M.; Kim, Woong-Ki

2018-01-01

Objective: HIV-1 infection of the brain and related cognitive impairment remain prevalent in HIV-1-infected individuals despite combination antiretroviral therapy. Sterile alpha motif and histidine-aspartate domain-containing protein 1 (SAMHD1) is a newly identified host restriction factor that blocks the replication of HIV-1 and other retroviruses in myeloid cells. Cell cycle-regulated phosphorylation at residue Thr592 and viral protein X (Vpx)-mediated degradation of SAMHD1 have been shown to bypass SAMHD1 restriction in vitro. Herein, we investigated expression and phosphorylation of SAMHD1 in vivo in relation to macrophage infection and proliferation during the neuropathogenesis of HIV-1 and simian immunodeficiency virus (SIV) encephalitis. Methods: Using brain and other tissues from uninfected and SIV-infected macaques with or without encephalitis, we performed immunohistochemistry, multilabel fluorescence microscopy and western blot to examine the expression, localization and phosphorylation of SAMHD1. Results: The number of SAMHD1+ nuclei increased in encephalitic brains despite the presence of Vpx. Many of these cells were perivascular macrophages, although subsets of SAMHD1+ microglia and endothelial cells were also observed. The SAMHD1+ macrophages were shown to be both infected and proliferating. Moreover, the presence of cycling SAMHD1+ brain macrophages was confirmed in the tissue of HIV-1-infected patients with encephalitis. Finally, western blot analysis of brain-protein extracts from SIV-infected macaques showed that SAMHD1 protein exists in the brain mainly as an inactive Thr592-phosphorylated form. Conclusion: The ability of SAMHD1 to act as a restriction factor for SIV/HIV in the brain is likely bypassed in proliferating brain macrophages through the phosphorylation-mediated inactivation, not Vpx-mediated degradation of SAMHD1. PMID:29698322

West Nile Virus Retinopathy and Associations with Long Term Neurological and Neurocognitive Sequelae.

PubMed

Hasbun, Rodrigo; Garcia, Melissa N; Kellaway, Judianne; Baker, Laura; Salazar, Lucrecia; Woods, Steven Paul; Murray, Kristy O

2016-01-01

West Nile virus (WNV) has emerged as an important vector-borne pathogen in North America, with more than 3 million estimated to have been infected. Retinopathy from WNV infection has been previously reported in acute cases, though those prior reports did not evaluate the risk of retinopathy based on clinical severity of neurologic disease. The purpose of this cross-sectional study was to perform comprehensive ophthalmological and neurological examinations on 111 patients with a history of West Nile virus infection and describe the ocular manifestations. Out of 111 patients, 27 (24%) had evidence for West Nile virus associated retinopathy (WNVR); this observation was higher (49%) in those patients who initially presented with encephalitis. Individuals with WNVR had more frequent involvement of the macula and peripheral involvement compared to those patients without WNVR (p<0.05). WNVR was also associated with a greater likelihood of abnormal reflexes on neurological exam, poorer learning, greater dependence in activities of daily living, and lower quality of life (p<0.05). WNVR was seen more frequently in elderly patients (age > 60 years), and was associated with higher rates of diabetes mellitus and a history of encephalitis (p<0.05). A multivariable logistic regression revealed that only a history of encephalitis was independently associated with WNVR [Adjusted Odds Ratio = 4.9 (1.8-13.2); p = 0.001]. Our study found that WNVR occurs in one fourth of patients with a history of WNV infection and is more frequently observed in those with apparent severe neurological sequelae (e.g., encephalitis). The clinical relevance of WNVR was supported by its associations with dependence in activities of daily living and lower quality of life. This unique evaluation of WNV patients included fundoscopic examinations and their associations with neurologic impairment. Our findings can be used during ophthalmological consultation for the evaluation, treatment and rehabilitation phases of care for WNV patients.

Herpes encephalitis is a disease of middle aged and elderly people: polymerase chain reaction for detection of herpes simplex virus in the CSF of 516 patients with encephalitis. The Study Group.

PubMed

Koskiniemi, M; Piiparinen, H; Mannonen, L; Rantalaiho, T; Vaheri, A

1996-02-01

To assess the diagnostic potential of the polymerase chain reaction (PCR) in herpes simplex virus (HSV) encephalitis. Samples of CSF from 516 patients with encephalitis were studied for HSV-DNA by PCR. Samples taken one to 29 days from the onset of symptoms from 38 patients (7.4%) were positive, 32 (6.2%) for HSV-1 and six (1.2%) for HSV-2. At follow up, eight of 28 patients studied were still HSV-PCR positive. A diagnostic serum:CSF antibody ratio to HSV but not to other viruses was detected in 25 of the 38 HSV-PCR positive patients thus supporting the initial PCR findings. Patients positive by HSV-PCR were concentrated in the age group > or = 40 years, and especially in patients aged 60-64 years, of whom nine of 24 (37.5%) were positive. The HSV-PCR was negative in all other patients with encephalitis of known or unknown aetiology. This group included 34 patients with a diagnostic serum:CSF antibody ratio to other viruses. A dual infection, HSV and another microbe, was considered possible in seven patients. The HSV-PCR is a rapid and useful diagnostic method during the early phase of encephalitis. It may be useful in monitoring the efficacy of treatment and allowing the recognition of new features in the appearance of herpes encephalitis. The HSV-PCR test and antibody determinations from serum and CSF are complementary methods, which should both be applied in pursuit of clinical laboratory diagnosis of these conditions.

Weather, host and vector — their interplay in the spread of insect-borne animal virus diseases

PubMed Central

Sellers, R. F.

1980-01-01

The spread of insect-borne animal virus diseases is influenced by a number of factors. Hosts migrate, move or are conveyed over long distances: vectors are carried on the wind for varying distances in search of hosts and breeding sites; weather and climate affect hosts and vectors through temperature, moisture and wind. As parasites of host and vector, viruses are carried by animals, birds and insects, and their spread can be correlated with the migration of hosts and the carriage of vectors on winds associated with the movements of the Intertropical Convergence Zone (ITCZ) and warm winds to the north and south of the limits of the ITCZ. The virus is often transmitted from a local cycle to a migratory cycle and back again. Examples of insect-borne virus diseases and their spread are analysed. Japanese, Murray Valley, Western equine, Eastern equine and St Louis encephalitis represent viruses transmitted by mosquito—bird or pig cycles. The areas experiencing infection with these viruses can be divided into a number of zones: A, B, C, D, E and F. In zone A there is a continuous cycle of virus in host and vector throughout the year; in zone B, there is an upsurge in the cycle during the wet season, but the cycle continues during the dry season; there is movement of infected vectors between and within zones A and B on the ITCZ and the virus is introduced to zone C by infected vectors on warm winds; persistence may occur in zone C if conditions are right. In zone D, virus is introduced each year by infected vectors on warm winds and the arrival of the virus coincides with the presence of susceptible nestling birds and susceptible piglets. The disappearance of virus occurs at the time when migrating mosquitoes and birds are returning to warmer climates. The virus is introduced to zone E only on occasions every 5-10 years when conditions are suitable. Infected hosts introduced to zone F do not lead to circulation of virus, since the climate is unsuitable for vectors. Zones A, B and C correspond to endemic and zones D and E to epidemic conditions. Similar zones can be recognized for African horse sickness, bluetongue, Ibaraki disease and bovine ephemeral fever — examples of diseases transmitted in a midge-mammal cycle. In zones A and B viruses are transported by infected midges carried on the wind in association with the movement of ITCZ and undergo cycles in young animals. In these zones and in zone C there is a continual movement of midges on the warm wind between one area and another, colonizing new sites or reinforcing populations of midges already present. Virus is introduced at times into fringe areas (zones D and E) and, as there is little resistance in the host, gives rise to clinical signs of disease. In some areas there is persistence during adverse conditions; in others, the virus is carried back to the endemic zones by infected midges or vectors. Examples of viruses maintained in a mosquito/biting fly—mammal cycle are Venezuelan equine encephalitis and vesicular stomatitis. These viruses enter a migratory cycle from a local cycle and the vectors in the migratory cycle are carried over long distances on the wind. Further examples of virus spread by movement of vectors include West Nile, Rift Valley fever, yellow fever, epizootic haemorrhagic disease of deer and Akabane viruses. In devising means of control it is essential to decide the relationship of host, vector and virus and the nature of the zone in which the area to be controlled lies. Because of the continual risk of reintroduction of infected vectors, it is preferable to protect the host by dipping, spraying or by vaccination rather than attempting to eliminate the local population of insects. PMID:6131919

Epidemic Spread of Usutu Virus in Southwest Germany in 2011 to 2013 and Monitoring of Wild Birds for Usutu and West Nile Viruses.

PubMed

Ziegler, Ute; Jöst, Hanna; Müller, Kerstin; Fischer, Dominik; Rinder, Monika; Tietze, Dieter Thomas; Danner, Klaus-Jürgen; Becker, Norbert; Skuballa, Jasmin; Hamann, Hans-Peter; Bosch, Stefan; Fast, Christine; Eiden, Martin; Schmidt-Chanasit, Jonas; Groschup, Martin H

2015-08-01

Mosquito-borne viruses are becoming an increasing threat for Europe. One of these viruses is Usutu virus (USUV), a single-stranded RNA virus belonging to the Japanese encephalitis virus group within the family Flaviviridae. Since the occurrence of USUV among wild birds in June, 2011, infected Blackbirds (Turdus merula) have frequently been found dead in southwest Germany, cumulating in a massive die-off. Moreover, other bird species (Strigiformes) in this region have been affected. In a first study, 209 of over 600 dead birds (wild birds and birds kept in aviaries) collected from 2011 to 2013 carried USUV, more than 88% of them Blackbirds. USUV had already been detected in 2010, one year before the epizooty, in a mosquito-based surveillance program in Germany. The main epidemic area of the USUV outbreak in wild birds in southwest Germany has been similar for the last three years. In a second study during 2011 to 2013, 902 live migratory and resident birds (representing 87 bird species belonging to 14 bird orders) from four different sampling sites were bled and tested serologically and by qPCR for West Nile virus (WNV) and USUV infections. No USUV or WNV genomes were detected. Some migratory birds (mainly long-distance migrants and some partial migrants) carried neutralizing antibodies against WNV as discriminated by USUV and WNV cross-neutralization tests. Only few resident birds showed relevant USUV-specific neutralizing antibodies. The occurrence of USUV in the Upper Rhine valley area of southwest Germany is a proof of principle for the incursion and spread of other arthropod-borne (arbo)-viruses along these routes. Therefore, monitoring studies in birds and mosquitoes for the presence of arboviruses in these areas are indispensable.

[Interaction of the Siberian and Far Eastern subtypes of tick-borne encephalitis virus in mammals with mixed infection. I. Factors influencing the type of interaction].

PubMed

Gerasimov, S G; Pogodina, V V; Kolyasnikova, N M; Karan, L S; Malenko, G V; Levina, L S

2011-01-01

Polytypic strains containing the fragments of genes of Siberian and Far Eastern tick-borne encephalitis (TBE) virus subtypes were isolated from the brain of fatal TBE patients, the blood of TBE patients, and Ixodes persulcatus ticks in the foci of concomitant circulation of the two subtypes. The interaction of the Siberian and Far Eastern TBE virus subtypes was studied in the neural phase of the infection of albino mice and Syrian hamsters in order to understand conditions for formation of these strains and their role in the etiology of acute TBE. Their viral progeny was genotyped by reverse transcription-polymerase chain reaction and fluorescence hybridization assay with genotype-specific probes. Mixed infection showed an effect of synergism, independent reproduction of the two subtypes in the brain and spleen, competitive exclusion of one subtype from the viral population. The type of the Interaction depended on the species of animals, the properties of partner strains, and the target organ.

Tick-borne encephalitis virus in dogs - is this an issue?

PubMed Central

2011-01-01

The last review on Tick-borne encephalitis (TBE) in dogs was published almost ten years ago. Since then, this zoonotic tick-borne arbovirus has been geographically spreading and emerging in many regions in Eurasia and continues to do so. Dogs become readily infected with TBE virus but they are accidental hosts not capable to further spread the virus. They seroconvert upon infection but they seem to be much more resistant to the clinical disease than humans. Apart from their use as sentinels in endemic areas, however, an increasing number of case reports appeared during the last decade thus mirroring the rising public health concerns. Owing to the increased mobility of people travelling to endemic areas with their companion dogs, this consequently leads to problems in recognizing and diagnosing this severe infection in a yet non-endemic area, simply because the veterinarians are not considering TBE. This situation warrants an update on the epidemiology, clinical presentation and possible preventions of TBE in the dog. PMID:21489255

[Strategy for choosing antibiotics for treating bacterial infections associated with chronic tick-borne encephalitis].

PubMed

Malenko, G V; Pogodina, V V; Frolova, M P; Ivannikova, T A

1996-01-01

The capacity of wide-spectrum antibiotics kefzol and ristomycin to activate the persisting tick-borne encephalitis (TBE) virus and cause an exacerbation of chronic process was investigated in Syrian hamsters in whom a prolonged (77 to 270 days) persistent TBE infection was induced by three TBE strains: Vasilchenko, V-383, and 205. The degree of antibiotic-induced activation was assessed using the criteria characterizing the reproduction and peculiarities of persisting TBE virus, immunodepression, and morphologic changes in the central nervous system. Effects of kefzol and ristomycin were compared with those of 8 antibiotics studied previously. Ristomycin, levomycetin (chloramphycin), penicillin, ampicillin (ampital), and levoridan were referred to drugs devoid of evident provoking effect. Kefzol (cefamezin), florimycin (viomycin), and kanamycin (kanamytrex) were characterized as weak activators and streptomycin and tetracycline as potent activators of the persisting TBE virus. These data may be used when selecting alternative agents for therapy of secondary bacterial infections concomitant with TBE.

Role of U.S. military research programs in the development of U.S.-licensed vaccines for naturally occurring infectious diseases.

PubMed

Kitchen, Lynn W; Vaughn, David W

2007-10-10

U.S. military physicians and researchers have collaborated in the development of eight U.S.-licensed vaccines since 1934, when product efficacy requirements were added to product safety requirements mandated in 1902. These vaccines include influenza (1945), rubella (1969), adenovirus types 4 and 7 (1980), meningococcus A, C, Y, W-135 (1981), hepatitis B (1981), oral typhoid (1989), Japanese encephalitis (1992), and hepatitis A (1995). Current efforts include new adenovirus and Japanese encephalitis vaccines, and vaccines to prevent dengue, diarrhea due to enterotoxigenic E. coli, Campylobacter, and Shigella, malaria, hemorrhagic fever with renal syndrome, scrub typhus, meningococcus type B, and HIV infection. All vaccines currently administered to U.S. military forces must be licensed by the U.S. Food and Drug Administration (FDA).

Serologic survey of domestic animals for zoonotic arbovirus infections in the Lacandón Forest region of Chiapas, Mexico.

PubMed

Ulloa, Armando; Langevin, Stanley A; Mendez-Sanchez, J D; Arredondo-Jimenez, Juan I; Raetz, Janae L; Powers, Ann M; Villarreal-Treviño, C; Gubler, Duane J; Komar, Nicholas

2003-01-01

A serologic survey in domestic animals (birds and mammals) was conducted in four communities located in the Lacandón Forest region of northeastern Chiapas, Mexico, during June 29 to July 1, 2001, with the objective to identify zoonotic arboviruses circulating in this area. We collected 202 serum samples from healthy domestic chickens, geese, ducks, turkeys, horses and cattle. The samples were tested by plaque-reduction neutralization test for antibodies to selected mosquito-borne flaviviruses (family Flaviviridae), including St. Louis encephalitis (SLE), Rocio (ROC), Ilheus (ILH), Bussuquara (BSQ), and West Nile (WN) viruses, and selected alphaviruses (family Togaviridae), including Western equine encephalitis (WEE), Eastern equine encephalomyelitis (EEE), and Venezuelan equine encephalitis (VEE) viruses. Neutralizing antibodies to SLE virus were detected in two (8%) of 26 turkeys, 15 (23%) of 66 cattle, and three (60%) of five horses. Antibodies to VEE virus were detected in 29 (45%) of 65 cattle. Because some of these animals were as young as 2 months old, we demonstrated recent activity of these two viruses. Sub-typing of the VEE antibody responses indicated that the etiologic agents of these infections belonged to the IE variety of VEE, which has been reported from other regions of Chiapas. WN virus-neutralizing antibodies were detected in a single cattle specimen (PRNT(90) = 1:80) that also circulated SLE virus-neutralizing antibodies (PRNT(90) = 1:20), suggesting that WN virus may have been introduced into the region. We also detected weak neutralizing activity to BSQ virus in four cattle and a chicken specimen, suggesting the presence of this or a closely related virus in Mexico. There was no evidence for transmission of the other viruses (ROC, ILH, EEE, WEE) in the study area.

TRIM79α, an interferon-stimulated gene product, restricts tick-borne encephalitis virus replication by degrading the viral RNA polymerase

PubMed Central

Taylor, R. Travis; Lubick, Kirk J.; Robertson, Shelly J.; Broughton, James P.; Bloom, Marshall E.; Bresnahan, Wade A.; Best, Sonja M.

2011-01-01

In response to virus infection, type I interferons (IFNs) induce several genes, most of whose functions are largely unknown. Here we show that the tripartite motif (TRIM) protein, TRIM79α, is an IFN-stimulated gene (ISG) product that specifically targets tick-borne encephalitis virus (TBEV), a Flavivirus that causes encephalitides in humans. TRIM79α restricts TBEV replication by mediating lysosome-dependent degradation of the flavivirus NS5 protein, an RNA-dependent RNA polymerase essential for virus replication. NS5 degradation was specific to tick-borne flaviviruses as TRIM79α did not recognize NS5 from West Nile virus (WNV) or inhibit WNV replication. In the absence of TRIM79α, IFN-β was less effective in inhibiting tick-borne flavivirus infection of mouse macrophages, highlighting the importance of a single virus-specific ISG in establishing an antiviral state. The specificity of TRIM79α for TBEV reveals a remarkable ability of the innate IFN response to discriminate between closely related flaviviruses. PMID:21925107