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Sample records for japanese encephalitis virus-infected

  1. Argonaute 2 Suppresses Japanese Encephalitis Virus Infection in Aedes aegypti.

    PubMed

    Sasaki, Toshinori; Kuwata, Ryusei; Hoshino, Keita; Isawa, Haruhiko; Sawabe, Kyoko; Kobayashi, Mutsuo

    2017-01-24

    There are three main innate immune mechanisms against viruses in mosquitoes. Infection with the flavivirus dengue virus is controlled by RNA interference (RNAi) and the JAK-STAT and Toll signaling pathways. This study showed that another flavivirus, Japanese encephalitis virus (JEV), did not invade the salivary glands of Aedes aegypti and that this may be a result of the innate immune resistance to the virus. Argonaute 2 (Ago2) plays a critical role in the RNAi pathway. To understand the mechanism of JEV resistance, we focused on Ago2 as a possible target of JEV. Here, we show that the expression of MyD88 (a mediator of Toll signaling) and Ago2 mRNAs was induced by JEV in the salivary glands of Ae. aegypti mosquitoes and that Ago2, JAK, and domeless (DOME) mRNAs were induced by JEV in the bodies of Ae. aegypti mosquitoes. Double-stranded (ds) Ago2 RNA enhanced JEV infection, and the virus was detected in salivary glands by immunofluorescence assay. In contrast, MyD88 dsRNA had no effect on JEV infection. These data suggest that Ago2 plays a crucial role in mediating the innate immune response of Ae. aegypti to JEV in a manner similar to that employed by dengue virus.

  2. Japanese encephalitis virus infection decrease endogenous IL-10 production: correlation with microglial activation and neuronal death.

    PubMed

    Swarup, Vivek; Ghosh, Joydeep; Duseja, Rachna; Ghosh, Soumya; Basu, Anirban

    2007-06-13

    The anti-inflammatory cytokine interleukin (IL)-10 is synthesized in the central nervous system (CNS) and acts to limit clinical symptoms of stroke, multiple sclerosis, Alzheimer's disease, meningitis, and the behavioral changes that occur during bacterial infections. Expression of IL-10 is critical during the course of most major diseases in the CNS and promotes survival of neurons and all glial cells in the brain by blocking the effects of proinflammatory cytokines and by promoting expression of cell survival signals. In order to assess functional importance of this cytokine in viral encephalitis we have exploited an experimental model of Japanese encephalitis (JE). We report for the first time that in Japanese encephalitis, there is a progressive decline in level of IL-10. The extent of progressive decrease in IL-10 level following viral infection is inversely proportional to the increase in the level of proinflammatory cytokines as well as negative consequences that follows viral infection.

  3. Disruption of in vitro endothelial barrier integrity by Japanese encephalitis virus-Infected astrocytes.

    PubMed

    Chang, Cheng-Yi; Li, Jian-Ri; Chen, Wen-Ying; Ou, Yen-Chuan; Lai, Ching-Yi; Hu, Yu-Hui; Wu, Chih-Cheng; Chang, Chen-Jung; Chen, Chun-Jung

    2015-05-08

    Blood-brain barrier (BBB) characteristics are induced and maintained by crosstalk between brain microvascular endothelial cells and neighboring cells. Using in vitro cell models, we previously found that a bystander effect was a cause for Japanese encephalitis-associated endothelial barrier disruption. Brain astrocytes, which neighbor BBB endothelial cells, play roles in the maintenance of BBB integrity. By extending the scope of relevant studies, a potential mechanism has been shown that the activation of neighboring astrocytes could be a cause of disruption of endothelial barrier integrity during the course of Japanese encephalitis viral (JEV) infection. JEV-infected astrocytes were found to release biologically active molecules that activated ubiquitin proteasome, degraded zonula occludens-1 (ZO-1) and claudin-5, and disrupted endothelial barrier integrity in cultured brain microvascular endothelial cells. JEV infection caused astrocytes to release vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), and matrix metalloproteinases (MMP-2/MMP-9). Our data demonstrated that VEGF and IL-6 released by JEV-infected astrocytes were critical for the proteasomal degradation of ZO-1 and the accompanying disruption of endothelial barrier integrity through the activation of Janus kinase-2 (Jak2)/signal transducer and activator of transcription-3 (STAT3) signaling as well as the induction of ubiquitin-protein ligase E3 component, n-recognin-1 (Ubr 1) in endothelial cells. MMP-induced endothelial barrier disruption was accompanied by MMP-mediated proteolytic degradation of claudin-5 and ubiquitin proteasome-mediated degradation of ZO-1 via extracellular VEGF release. Collectively, these data suggest that JEV infection could activate astrocytes and cause release of VEGF, IL-6, and MMP-2/MMP-9, thereby contributing, in a concerted action, to the induction of Japanese encephalitis-associated BBB breakdown. GLIA 2015.

  4. Japanese Encephalitis Virus Infection Results in Transient Dysfunction of Memory Learning and Cholinesterase Inhibition.

    PubMed

    Chauhan, Prashant Singh; Khanna, Vinay Kumar; Kalita, Jayantee; Misra, Usha Kant

    2016-07-22

    Cholinergic system has an important role in memory and learning. Abnormal cognitive and behavioral changes have been reported in Japanese encephalitis (JE), but their basis has not been comprehensively evaluated. In this study, we report memory and learning and its association with acetylcholinesterase (AChE) activity, JE virus titer, and with histopathological observations in a rat model of JE. Wistar rats were intracerebrally inoculated on 12th day with 3 × 10(6) pfu/ml of JE virus. Memory and learning were assessed by the active and passive avoidance tests on 10, 33, and 48 days post inoculation (dpi). After 10, 33, and 48 dpi AChE activity, Japanese encephalitis virus (JEV) titer and histopathological changes were studied in the frontal cortex, thalamus, midbrain, cerebellum, and hippocampus. There was significant impairment in memory and learning on 10 dpi which started improving from 33 dpi to 48 dpi by active avoidance test. Passive avoidance test showed decrease in transfer latency time of retention trial compared to acquisition on first, second, and third retention day trial compared to controls. AChE inhibition was more marked in the hippocampus, frontal cortex, and cerebellum on 10 dpi. However, AChE activity started improving from 33 dpi to 48 dpi. AChE activity in the thalamus and midbrain correlated with active avoidance test on 10 dpi and 33 dpi. Histopathological studies also revealed improvement on 33 and 48 compared to 10 dpi. The present study demonstrates transient memory and learning impairment which was associated with reduction in AChE, JEV titer, and damage in different brain regions of JEV infected rats.

  5. IC-51, an injectable vaccine for the prevention of Japanese encephalitis virus infection.

    PubMed

    Jones, Taff

    2009-02-01

    The mosquito-borne Japanese encephalitis (JE) virus is the major etiological agent of viral encephalitis in children living in South-East Asia, causing comas, seizures and Parkinson's disease-like movement disorders. Travelers and military personnel visiting the region are also highly susceptible to the disease. As the population in South-East Asia increases, more land is irrigated to produce rice paddies (the ideal breeding habitat for mosquitoes), and pig breeding (a zoonotic host for mosquitoes) becomes more widespread. Given the exponential growth in tourism to the region and the globalization of business and commerce, an enhanced requirement for mass vaccination exists. In the West, the current licensed vaccine against JE, JE-VAX, has been highly effective; however, the use of mouse brain-derived virus has been linked to cases of acute disseminated encephalomyelitis. Intercell AG, under license from VaccGen International LLC, is developing IC-51, a formalin-inactivated vaccine derived from cell culture-based attenuated virus that has been adapted to grow in Vero cells (African green monkey kidney cells). In extensive clinical trials performed to date, IC-51 was safe, with mild to moderate adverse events reported. In terms of immunogenicity, IC-51 was highly effective, demonstrating rapid seroconversion rates and long-term maintenance of geometric mean titers that exceeded the protective titer. The results suggests that IC-51 is fully compliant with the stringent regulatory requirements set by the WHO, has an acceptable safety profile and is non-inferior to JE-VAX.

  6. Mosquito distribution and Japanese encephalitis virus infection in the immigration bird (Asian open-billed stork) nested area in Pathum Thani province, central Thailand.

    PubMed

    Tiawsirisup, Sonthaya; Nuchprayoon, Surang

    2010-03-01

    Japanese encephalitis virus infection is a mosquito-borne emerging or re-emerging infectious disease in several countries. The ecology of this virus in nature includes amplifying avian or mammal hosts and mosquito vectors. Infected immigration birds from epidemic areas may play important roles in the outbreak of the disease. The prevalence is high during the raining season in Thailand and human cases have been reported from several provinces including Bangkok suburbs. This study was conducted to investigate the mosquito distribution and Japanese encephalitis virus infection in the immigration bird (Asian open-billed stork) nested area, Pathum Thani province, central Thailand. Mosquitoes were collected by using CO(2)-baited Centers for disease control and prevention (CDC) light traps, and dry ice was used as a source of CO(2) to attract mosquitoes from March 2008 to January 2009. Eight traps were operated from 4 p.m. until 7 a.m. on each study day. There were seven genera collected: Aedes, Anopheles, Armigeres, Coquillettidia, Culex, Mansonia, and Uranotaenia. Culex tritaeniorhynchus was the most collected species in each month, except November, in which Culex gelidus was the most collected species. Sixty pools of C. gelidus and of C. tritaeniorhynchus, each of which had 50 mosquitoes, were tested for Japanese encephalitis virus infection by using reverse transcription polymerase chain reactions; however, none of them was infected with the virus.

  7. Susceptibility of Human Embryonic Stem Cell-Derived Neural Cells to Japanese Encephalitis Virus Infection

    PubMed Central

    Shen, Shih-Cheng; Shen, Ching-I; Lin, Ho; Chen, Chun-Jung; Chang, Chia-Yu; Chen, Sheng-Mei; Lee, Hsiu-Chin; Lai, Ping-Shan; Su, Hong-Lin

    2014-01-01

    Pluripotent human embryonic stem cells (hESCs) can be efficiently directed to become immature neuroepithelial precursor cells (NPCs) and functional mature neural cells, including neurotransmitter-secreting neurons and glial cells. Investigating the susceptibility of these hESCs-derived neural cells to neurotrophic viruses, such as Japanese encephalitis virus (JEV), provides insight into the viral cell tropism in the infected human brain. We demonstrate that hESC-derived NPCs are highly vulnerable to JEV infection at a low multiplicity of infection (MOI). In addition, glial fibrillary acid protein (GFAP)-expressing glial cells are also susceptible to JEV infection. In contrast, only a few mature neurons were infected at MOI 10 or higher on the third day post-infection. In addition, functional neurotransmitter-secreting neurons are also resistant to JEV infection at high MOI. Moreover, we discover that vimentin intermediate filament, reported as a putative neurovirulent JEV receptor, is highly expressed in NPCs and glial cells, but not mature neurons. These results indicate that the expression of vimentin in neural cells correlates to the cell tropism of JEV. Finally, we further demonstrate that membranous vimentin is necessary for the susceptibility of hESC-derived NPCs to JEV infection. PMID:25517725

  8. Inhibition of ERK and proliferation in NK cell lines by soluble HLA-E released from Japanese encephalitis virus infected cells.

    PubMed

    Shwetank; Date, Onkar Sanjay; Carbone, Ennio; Manjunath, Ramanathapuram

    2014-11-01

    Productive infection of human endothelial cells with Japanese encephalitis virus (JEV), a single stranded RNA virus induces shedding of sHLA-E. We show here that sHLA-E that is released upon infection with this flavivirus can inhibit IL-2 and PMA mediated ERK 1/2 phosphorylation in two NK cell lines, Nishi and NKL. Virus infected or IFN-γ treated cell culture supernatants containing sHLA-E were found to partially inhibit IL-2 mediated induction of CD25 molecules on NKL cells. It was also found that sHLA-E could inhibit IL-2 induced [(3)H]-thymidine incorporation suggesting that, similar to cell surface expressed HLA-E, sHLA-E could also inhibit NK cell responses. Hence JEV-induced shedding of sHLA-E needs further investigation to better understand immune responses in JEV infections since it may have a role in viral evasion of NK cell responses.

  9. Differential Diagnosis of Japanese Encephalitis Virus Infections with the Inbios JE Detect™ and DEN Detect™ MAC-ELISA Kits

    PubMed Central

    Johnson, Barbara W.; Goodman, Christin H.; Jee, Youngmee; Featherstone, David A.

    2016-01-01

    Japanese encephalitis virus (JEV) is the leading cause of pediatric viral neurological disease in Asia. The JEV-specific IgM antibody-capture enzyme-linked immunosorbent assay (MAC-ELISA) in cerebrospinal fluid (CSF) and serum is the recommended method of laboratory diagnosis, but specificity of JEV MAC-ELISA can be low due to cross-reactivity. To increase the specificity of the commercially available JE Detect™ MAC-ELISA (JE Detect), a differential testing algorithm was developed in which samples tested by JE Detect with positive results were subsequently tested by the DEN Detect™ MAC-ELISA (DEN Detect) kit, and results of both tests were used to make the final interpretation. The testing algorithm was evaluated with a reference panel of serum and CSF samples submitted for confirmatory testing. In serum, the false Japanese encephalitis (JE) positive rate was reduced, but sequential testing in CSF resulted in reduced JE specificity, as true JEV+ CSF samples had positive results by both JE Detect and DEN Detect and were classified as JE− (dengue virus [DENV]+). Differential diagnosis of JE by sequential testing with JE Detect and DEN Detect increased specificity for JE in serum, but more data with CSF is needed to make a final determination on the usefulness of this testing algorithm for CSF. PMID:26856911

  10. Design and evaluation of a multi-epitope peptide against Japanese encephalitis virus infection in BALB/c mice.

    PubMed

    Wei, Jian-chao; Huang, Yi-zhu; Zhong, Deng-ke; Kang, Le; Ishag, Hassan; Mao, Xiang; Cao, Rui-bing; Zhou, Bin; Chen, Pu-yan

    2010-06-11

    Epitope-based vaccination is a promising means to achieve protective immunity and to avoid immunopathology in Japanese encephalitis virus (JEV) infection. Several B-cell and T-cell epitopes have been mapped to the E protein of JEV, and they are responsible for the elicitation of the neutralizing antibodies and CTLs that impart protective immunity to the host. In the present study, we optimized a proposed multi-epitope peptide (MEP) using an epitope-based vaccine strategy, which combined six B-cell epitopes (amino acid residues 75-92, 149-163, 258-285, 356-362, 373-399 and 397-403) and two T-cell epitopes (amino acid residues 60-68 and 436-445) from the E protein of JEV. This recombinant protein was expressed in Escherichia coli, named rMEP, and its protective efficacy against JEV infection was assessed in BALB/c mice. The results showed that rMEP was highly immunogenic and could elicit high titer neutralizing antibodies and cell-mediated immune responses. It provided complete protection against lethal challenge with JEV in mice. Our findings indicate that the multi-epitope vaccine rMEP may be an attractive candidate vaccine for the prevention of JEV infection.

  11. Japanese viral encephalitis

    PubMed Central

    Tiroumourougane, S; Raghava, P; Srinivasan, S

    2002-01-01

    One of the leading causes of acute encephalopathy in children in the tropics is Japanese encephalitis (JE). Transmitted by the culex mosquito, this neurotropic virus predominately affects the thalamus, anterior horns of the spinal cord, cerebral cortex, and cerebellum. It mainly affects children <15 years and is mostly asymptomatic. The occasional symptomatic child typically presents with a neurological syndrome characterised by altered sensorium, seizures, and features of intracranial hypertension. Aetiological diagnosis is based on virus isolation or demonstration of virus specific antigen or antibodies in the cerebrospinal fluid/blood. Though no antiviral drug is available against JE, effective supportive management can improve the outcome. Control of JE involves efficient vector control and appropriate use of vaccines. PMID:11930023

  12. Experimental St. Louis encephalitis virus infection of sloths and cormorants.

    PubMed

    Seymour, C; Kramer, L D; Peralta, P H

    1983-07-01

    Experimental infection of 11 Bradypus variegatus and Choloepus hoffmanni sloths with St. Louis encephalitis (SLE) virus produced detectable viremias of seven to 27 (median 13) days duration and maximum titers of 2.7 to 6.5 (median 5.1) log10 median suckling mouse intracranial lethal doses (SMicLD50) per ml. Experimental SLE viremia onset was delayed and maximum titer depressed in two sloths concurrently infected with naturally acquired viruses. SLE viremias in four experimentally inoculated cormorants Phalacrocorax olivaceus were shorter, and of equal or lower titer, than in sloths. Colonized Culex pipiens quinquefasciatus mosquitoes were infected by feeding on sloths circulating at least 4.8 log10 SMicLD50 of SLE virus per ml, and subsequently transmitted the infection to mice and chicks. An uninoculated baby Bradypus became infected by contact transmission from its mother. The antibody response of sloths to SLE virus was slow, being undetectable until several weeks post-inoculation. However, both sloth species developed high and long-lasting neutralizing and hemagglutination-inhibition antibody titers. The complement-fixation antibody response in Bradypus was lower and slower to develop than in Choloepus. Sloths with naturally acquired SLE virus antibody did not become detectably viremic after experimental inoculation. Neither sloths nor cormorants become overly ill from SLE virus infection.

  13. Japanese Encephalitis: Frequently Asked Questions

    MedlinePlus

    ... by a virus spread by infected mosquitoes in Asia and the western Pacific. JE virus is one ... Where does Japanese encephalitis occur? JE occurs in Asia and parts of the western Pacific. It usually ...

  14. Overview: Japanese encephalitis.

    PubMed

    Misra, Usha Kant; Kalita, Jayantee

    2010-06-01

    Japanese encephalitis (JE) is one of the most important endemic encephalitis in the world especially in Eastern and Southeastern Asia. JE affects over 50,000 patients and results in 15,000 deaths annually. JE virus is a single stranded positive sense RNA virus belonging to family flaviviridae. JE virus is transmitted through a zoonotic cycle between mosquitoes, pigs and water birds. Humans are accidentally infected and are a dead end host because of low level and transient viremia. In the northern region, large epidemics occur during summers whereas in the southern region JE tends to be endemic: cases occur throughout the year with a peak in the rainy season. Occurrence of JE is more closely related to temperature than to humidity. JE is regarded as a disease of children in the endemic areas but in the newly invaded areas, it affects both the adults and children because of the absence of protective antibodies. For every patient of JE, there are large numbers of subclinical cases (25-1000). Symptomatic JEV infection manifests with nonspecific febrile illness, aseptic meningitis or encephalitis. Encephalitis manifests with altered sensorium, seizures and focal neurological deficit. Acute flaccid paralysis may occur due to anterior horn cell involvement. A wide variety of movement disorders especially transient Parkinsonian features and dystonia (limb, axial, orofacial) are reported in 20-60% patients. JE mainly affects thalamus, corpus striatum, brainstem and spinal cord as revealed by MRI and on autopsy studies. Coinfection of JE and cysticercosis occurs because of the important role of pigs in the life cycle of both JEV and cysticercosis. Laboratory diagnosis of JE is by IgM capture ELISA, which has high sensitivity and specificity. In the absence of specific antiviral therapy, JE is managed by symptomatic and supportive therapies and preventive measures. Purified formalin inactivated mouse brain derived vaccine and live attenuated vaccine (SA 14-14-2) are

  15. A Prospective Assessment of the Accuracy of Commercial IgM ELISAs in Diagnosis of Japanese Encephalitis Virus Infections in Patients with Suspected Central Nervous System Infections in Laos

    PubMed Central

    Moore, Catrin E.; Blacksell, Stuart D.; Taojaikong, Thaksinaporn; Jarman, Richard G.; Gibbons, Robert V.; Lee, Sue J.; Chansamouth, Vilada; Thongpaseuth, Soulignasack; Mayxay, Mayfong; Newton, Paul N.

    2012-01-01

    Japanese encephalitis virus (JEV) is a major cause of encephalitis in Asia. We estimated the diagnostic accuracy of two anti-JEV immunoglobulin M (IgM) enzyme-linked immunosorbent assays (ELISAs) (Panbio and XCyton JEVCheX) compared with a reference standard (AFRIMS JEV MAC ELISA) in a prospective study of the causes of central nervous system infections in Laos. Cerebrospinal fluid (CSF; 515 patients) and serum samples (182 patients) from those admitted to Mahosot Hospital, Vientiane, were tested. The CSF from 14.5% of acute encephalitis syndrome (AES) patients and 10.1% from those with AES and meningitis were positive for anti-JEV IgM in the reference ELISA. The sensitivities for CSF were 65.4% (95% confidence interval [CI] = 51–78) (Xcyton), 69.2% (95% CI = 55–81) (Panbio), however 96.2% (95% CI = 87–100) with Panbio Ravi criteria. Specificities were 89–100%. For admission sera from AES patients, sensitivities and specificities of the Panbio ELISA were 85.7% (95% CI = 42–100%) and 92.9% (95% CI = 83–98%), respectively. PMID:22764310

  16. [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.

  17. Evaluation of chimeric DNA vaccines consisting of premembrane and envelope genes of Japanese encephalitis and dengue viruses as a strategy for reducing induction of dengue virus infection-enhancing antibody response.

    PubMed

    Sjatha, Fithriyah; Kuwahara, Miwa; Sudiro, T Mirawati; Kameoka, Masanori; Konishi, Eiji

    2014-02-01

    Neutralizing antibodies induced by dengue virus (DENV) infection show viral infection-enhancing activities at sub-neutralizing doses. On the other hand, preimmunity against Japanese encephalitis virus (JEV), a congener of DENV, does not increase the severity of DENV infection. Several studies have demonstrated that neutralizing epitopes in the genus Flavivirus are mainly located in domain III (DIII) of the envelope (E) protein. In this study, chimeric premembrane and envelope (prM-E) gene-based expression plasmids of JEV and DENV1 with DIII substitution of each virus were constructed for use as DNA vaccines and their immunogenicity evaluated. Sera from C3H/He and ICR mice immunized with a chimeric gene containing DENV1 DIII on a JEV prM-E gene backbone showed high neutralizing antibody titers with less DENV infection-enhancing activity. Our results confirm the applicability of this approach as a new dengue vaccine development strategy.

  18. Recent advances in Japanese encephalitis

    PubMed Central

    Basu, Anirban; Dutta, Kallol

    2017-01-01

    Japanese encephalitis is a flaviviral disease that is endemic to the South, Southeast Asia, and Asia Oceania regions. Given that about 60% of the world’s population (about 7.4 billion) resides in this region (about 4.4 billion), this disease poses a significant threat to global health. Active vaccination campaigns conducted in endemic countries have led to a decrease in the number of reported cases over the years. In this article, we strive to briefly highlight recent advances in understanding the role of microRNAs in disease pathology, focus on providing brief summaries of recent clinical trials in the field of Japanese encephalitis therapeutics, and review the current prophylactic strategies. PMID:28357054

  19. Evaluation of a dengue IgG indirect enzyme-linked immunosorbent assay and a Japanese encephalitis IgG indirect enzyme-linked immunosorbent assay for diagnosis of secondary dengue virus infection.

    PubMed

    Inoue, Shingo; Alonzo, Maria T G; Kurosawa, Yae; Mapua, Cynthia A; Reyes, Joyce D; Dimaano, Efren M; Alera, Maria Theresa P; Saito, Mariko; Oishi, Kazunori; Hasebe, Futoshi; Matias, Ronald R; Natividad, Filipinas F; Morita, Kouichi

    2010-03-01

    To establish a new method for the diagnosis of dengue secondary infection, 187 serum samples from the patients with dengue secondary infection, 40 serum samples from the patients with dengue primary infection, and 44 serum samples from the healthy volunteers were tested using the dengue IgG indirect enzyme-linked immunosorbent assay (DEN IgG ELISA). The results of the test were compared with those from the dengue hemagglutination inhibition (DEN HI) test, which has been recommended as the gold standard by the World Health Organization (WHO, 1997). Japanese encephalitis IgG indirect ELISA (JE IgG ELISA) was also performed to measure anti-flavivirus IgG, which cross-reacts with the Japanese encephalitis virus, to test the possibility of an alternative to DEN IgG ELISA. The results of DEN IgG and JE IgG ELISAs were highly correlated with those of the DEN HI test. In the DEN IgG ELISA, a titer of 1:29,000 was the cut-off value for the diagnosis of dengue secondary infection (91.5% accuracy [95% confidence interval, CI], 90.9% sensitivity [95%CI], and 92.9% specificity [95%CI]). A titer of 1:52,000 was the cut-off value for dengue secondary infection using JE IgG ELISA (95.6% accuracy [95%CI], 98.9% sensitivity [95%CI], and 88.1% specificity [95%CI]). In conclusion, this study confirmed that the results of both DEN IgG and JE IgG ELISAs were highly correlated with the results of DEN HI test. Thus, these ELISAs are simple, rapid, sensitive, and quantitative tests that can be used in the determination of dengue secondary infection.

  20. DC-SIGN as an attachment factor mediates Japanese encephalitis virus infection of human dendritic cells via interaction with a single high-mannose residue of viral E glycoprotein.

    PubMed

    Wang, Ping; Hu, Kai; Luo, Sukun; Zhang, Mudan; Deng, Xu; Li, Chang; Jin, Wei; Hu, Bodan; He, Siyi; Li, Mei; Du, Tao; Xiao, Gengfu; Zhang, Bo; Liu, Yalan; Hu, Qinxue

    2016-01-15

    The skin-resident dendritic cells (DCs) are thought to be the first defender to encounter incoming viruses and likely play a role in Japanese encephalitis virus (JEV) early infection. In the current study, following the demonstration of JEV productive infection in DCs, we revealed that the interaction between JEV envelope glycoprotein (E glycoprotein) and DC-SIGN was important for such infection as evidenced by antibody neutralization and siRNA knockdown experiments. Moreover, the high-mannose N-linked glycan at N154 of E glycoprotein was shown to be crucial for JEV binding to DC-SIGN and subsequent internalization, while mutation of DC-SIGN internalization motif did not affect JEV uptake and internalization. These data together suggest that DC-SIGN functions as an attachment factor rather than an entry receptor for JEV. Our findings highlight the potential significance of DC-SIGN in JEV early infection, providing a basis for further understanding how JEV exploits DC-SIGN to gain access to dendritic cells.

  1. Venezuelan equine encephalitis virus infection of spiny rats.

    PubMed

    Carrara, Anne-Sophie; Gonzales, Gonzales; Ferro, Cristina; Tamayo, Margarita; Aronson, Judith; Paessler, Slobodan; Anishchenko, Michael; Boshell, Jorge; Weaver, Scott C

    2005-05-01

    Enzootic strains of Venezuelan equine encephalitis virus (VEEV) circulate in forested habitats of Mexico, Central, and South America, and spiny rats (Proechimys spp.) are believed to be the principal reservoir hosts in several foci. To better understand the host-pathogen interactions and resistance to disease characteristic of many reservoir hosts, we performed experimental infections of F1 progeny from Proechimys chrysaeolus collected at a Colombian enzootic VEEV focus using sympatric and allopatric virus strains. All animals became viremic with a mean peak titer of 3.3 log10 PFU/mL, and all seroconverted with antibody titers from 1:20 to 1:640, which persisted up to 15 months. No signs of disease were observed, including after intracerebral injections. The lack of detectable disease and limited histopathologic lesions in these animals contrast dramatically with the severe disease and histopathologic findings observed in other laboratory rodents and humans, and support their role as reservoir hosts with a long-term coevolutionary relationship to VEEV.

  2. Establishment of an Algorithm Using prM/E- and NS1-Specific IgM Antibody-Capture Enzyme-Linked Immunosorbent Assays in Diagnosis of Japanese Encephalitis Virus and West Nile Virus Infections in Humans.

    PubMed

    Galula, Jedhan U; Chang, Gwong-Jen J; Chuang, Shih-Te; Chao, Day-Yu

    2016-02-01

    The front-line assay for the presumptive serodiagnosis of acute Japanese encephalitis virus (JEV) and West Nile virus (WNV) infections is the premembrane/envelope (prM/E)-specific IgM antibody-capture enzyme-linked immunosorbent assay (MAC-ELISA). Due to antibody cross-reactivity, MAC-ELISA-positive samples may be confirmed with a time-consuming plaque reduction neutralization test (PRNT). In the present study, we applied a previously developed anti-nonstructural protein 1 (NS1)-specific MAC-ELISA (NS1-MAC-ELISA) on archived acute-phase serum specimens from patients with confirmed JEV and WNV infections and compared the results with prM/E containing virus-like particle-specific MAC-ELISA (VLP-MAC-ELISA). Paired-receiver operating characteristic (ROC) curve analyses revealed no statistical differences in the overall assay performances of the VLP- and NS1-MAC-ELISAs. The two methods had high sensitivities of 100% but slightly lower specificities that ranged between 80% and 100%. When the NS1-MAC-ELISA was used to confirm positive results in the VLP-MAC-ELISA, the specificity of serodiagnosis, especially for JEV infection, was increased to 90% when applied in areas where JEV cocirculates with WNV, or to 100% when applied in areas that were endemic for JEV. The results also showed that using multiple antigens could resolve the cross-reactivity in the assays. Significantly higher positive-to-negative (P/N) values were consistently obtained with the homologous antigens than those with the heterologous antigens. JEV or WNV was reliably identified as the currently infecting flavivirus by a higher ratio of JEV-to-WNV P/N values or vice versa. In summary of the above-described results, the diagnostic algorithm combining the use of multiantigen VLP- and NS1-MAC-ELISAs was developed and can be practically applied to obtain a more specific and reliable result for the serodiagnosis of JEV and WNV infections without the need for PRNT. The developed algorithm should provide great

  3. Encephalitis

    MedlinePlus

    ... encephalitis virus Echovirus Japanese encephalitis, which occurs in Asia West Nile virus After the virus enters the ... are traveling to places such as parts of Asia, where Japanese encephalitis is found. Vaccinate animals to ...

  4. Preferential immune response to virion surface glycoproteins by caprine arthritis-encephalitis virus-infected goats.

    PubMed Central

    Johnson, G C; Barbet, A F; Klevjer-Anderson, P; McGuire, T C

    1983-01-01

    Six months after inoculation with caprine arthritis-encephalitis virus, the serum and synovial fluid of virus-infected goats had antibodies to [35S]methionine-labeled viral proteins with apparent molecular weights of 125,000, 90,000, 28,000, and 15,000. The 125,000-, 90,000-, and 15,000-molecular-weight methionine-labeled proteins were identified as virion surface glycoproteins by lactoperoxidase iodination and galactose oxidase-boro[3H]hydride reduction labeling techniques. Radioimmunoassay antibody titers to purified p28, the most abundant viral structural protein, averaged 1:182 in synovial fluid and 1:67 in serum 6 months after inoculation. High dilutions of serum and synovial fluid reacted with gp90 and gp125 electroblotted onto nitrocellulose paper from polyacrylamide gels. Anti-gp90 activity was detected at dilutions with an immunoglobulin G content of 0.02 to 11 micrograms, whereas antibody to p28, when detectable on Western blots, was present in samples with an immunoglobulin G content of 0.1 to 2 mg, representing 100- to 1,000-fold-greater titers of antibody to the surface glycoprotein. Synovial fluids often contained more anti-gp90 antibody than did sera. Immunoprecipitation of lactoperoxidase-iodinated virus confirmed the presence of high antibody titers to the two virion surface glycoproteins. Because antiviral gp90 and gp125 antibody is abundant in the synovial fluid of infected goats, it probably contributes to the high immunoglobulin G1 concentrations seen at this site 6 months after caprine arthritis-encephalitis virus infection. Images PMID:6307878

  5. A large outbreak of Japanese encephalitis predominantly among adults in northern region of West Bengal, India.

    PubMed

    Gurav, Yogesh K; Bondre, Vijay P; Tandale, Babasaheb V; Damle, Rekha G; Mallick, Sanjay; Ghosh, Uday S; Nag, Shankha S

    2016-11-01

    Unusual rise of acute encephalitis syndrome cases (AES) were reported in July 2014 in the northern region of West Bengal, India. Investigations were carried out to characterize the outbreak and to identify the associated virus etiology. This observational study is based on 398 line listed AES cases, mostly (70.8%, 282/398) adults, with case fatality ratio of 28.9% (115/398). Japanese encephalitis virus infection was detected in 134 (49.4%) among 271 AES cases tested and most of them (79.1%, 106/134) were adults. The study reports a large outbreak of genotype III Japanese encephalitis among adults in northern region of West Bengal, India. J. Med. Virol. 88:2004-2011, 2016. © 2016 Wiley Periodicals, Inc.

  6. Hemiplegia: an initial manifestation of Japanese encephalitis.

    PubMed

    Nalini, A; Arunodaya, G R; Taly, A B; Swamy, H S; Vasudev, M K

    2003-09-01

    A 7-year-old boy from an area endemic to Japanese encephalitis (JE) manifested with acute febrile illness, left hemiplegia and preserved consciousness during the prodromal phase of illness. The child developed features of encephalitis 48 hours after the onset of hemiplegia. IgM MAC ELISA for JE virus revealed high titers in the serum and cerebrospinal fluid suggestive of JE. MRI of the brain showed asymmetrical bilateral thalamic hyperintense lesions on T2 weighted image, considered diagnostic of JE. Hemiplegia during the prodromal phase or as an initial symptom of JE is rather unusual.

  7. Pathogenesis of Aerosolized Eastern Equine Encephalitis Virus Infection in Guinea Pigs

    DTIC Science & Technology

    2009-01-01

    infected animals and humans [1-3]. The related alphaviruses Venezuelan equine encephalitis virus (VEEV) and western equine encephalitis virus (WEEV) also...viruses [4] and experimental studies in animals have demonstrated that all three alphaviruses are infectious by the aerosol route and are considered a...associ- ated with EEEV infection are the most severe of any alphavirus , with an estimated mortality rate in humans of 30% for the North American strains

  8. The impact of climate on Japanese encephalitis.

    PubMed

    Hsu, S M; Yen, A M F; Chen, T H H

    2008-07-01

    The aim of this study was to assess the change of seasonal pattern of Japanese encephalitis (JE) cases in the post-vaccination period and to elucidate whether the lagged climate variables (precipitation and temperature) were associated with occurrence of JE after adjustment for seasonal pattern, time trend, geographic areas, pig density, vaccination coverage rate for humans, and time dependence of time-series numbers of JE cases. A total of 287 confirmed JE cases between 1991 and 2005 were collected, together with monthly data on socio-ecological archival data including climate, pig density and vaccination. A time-series generalized autoregressive Poisson regression model was used to achieve the objectives. The rate of JE increased from 1998 onwards. The seasonal pattern on occurrence of JE cases clustered between May and August during the period from 1991 to 2005 in Taiwan. In each geographic area, monitoring temperature and precipitation, two possible proxy variables for mosquito density, in conjunction with seasonal factors and pig density is of assistance in forecasting JE epidemics.

  9. A new tick-borne encephalitis-like virus infecting New England deer ticks, Ixodes dammini.

    PubMed Central

    Telford, S. R.; Armstrong, P. M.; Katavolos, P.; Foppa, I.; Garcia, A. S.; Wilson, M. L.; Spielman, A.

    1997-01-01

    To determine if eastern North American Ixodes dammini, like related ticks in Eurasia, maintain tick-borne encephalitis group viruses, we analyzed ticks collected from sites where the agent of Lyme disease is zoonotic. Two viral isolates were obtained by inoculating mice with homogenates from tick salivary glands. The virus, which was described by reverse transcriptase polymerase chain reaction and direct sequencing of the amplification products, was similar to, but distinct from, Powassan virus and is provisionally named "deer tick virus." Enzootic tick-borne encephalitis group viruses accompany the agents of Lyme disease, babesiosis, and granulocytic ehrlichiosis in a Holarctic assemblage of emergent deer tick pathogens. PMID:9204297

  10. Incidence of dengue virus infection among Japanese travellers, 2006 to 2010

    PubMed Central

    Arima, Yuzo; Shimada, Tomoe; Matsui, Tamano; Tada, Yuki; Okabe, Nobuhiko

    2012-01-01

    Introduction Dengue continues to be a global public health concern. In Japan, although dengue cases are currently seen only among travellers returning from endemic areas, the number of reported cases is rising according to the national case-based surveillance system. We evaluated the characteristics of dengue cases imported into Japan and the relationship between the incidence of infection and season of travel to popular destinations. Methods Dengue cases reported to the national surveillance system were retrospectively examined. The number of reported cases per number of Japanese travellers to a dengue-endemic country was calculated to estimate the country-specific incidence of imported dengue virus infection. The incidence of dengue infection among Japanese travellers was compared between dengue high season and low season in each country using relative risk (RR) and associated 95% confidence intervals (CI). Results Among 540 Japanese residents who were reported as dengue cases from 2006 to 2010, the majority had travelled to Indonesia, India, the Philippines and Thailand. The RR of dengue infection among Japanese travellers during dengue high season versus low season was 4.92 (95% CI: 3.01–8.04) for the Philippines, 2.76 (95% CI: 1.67–4.54) for Thailand and 0.37 (95% CI: 0.15–0.92) for Indonesia. Discussion Overall, higher incidence of imported cases appeared to be related to historic dengue high seasons. Travellers planning to visit dengue-endemic countries should be aware of historic dengue seasonality and the current dengue situation. PMID:23908911

  11. The Ubiquitin Proteasome System Plays a Role in Venezuelan Equine Encephalitis Virus Infection

    PubMed Central

    Amaya, Moushimi; Keck, Forrest; Lindquist, Michael; Voss, Kelsey; Scavone, Lauren; Kehn-Hall, Kylene; Roberts, Brian; Bailey, Charles; Schmaljohn, Connie; Narayanan, Aarthi

    2015-01-01

    Many viruses have been implicated in utilizing or modulating the Ubiquitin Proteasome System (UPS) to enhance viral multiplication and/or to sustain a persistent infection. The mosquito-borne Venezuelan equine encephalitis virus (VEEV) belongs to the Togaviridae family and is an important biodefense pathogen and select agent. There are currently no approved vaccines or therapies for VEEV infections; therefore, it is imperative to identify novel targets for therapeutic development. We hypothesized that a functional UPS is required for efficient VEEV multiplication. We have shown that at non-toxic concentrations Bortezomib, a FDA-approved inhibitor of the proteasome, proved to be a potent inhibitor of VEEV multiplication in the human astrocytoma cell line U87MG. Bortezomib inhibited the virulent Trinidad donkey (TrD) strain and the attenuated TC-83 strain of VEEV. Additional studies with virulent strains of Eastern equine encephalitis virus (EEEV) and Western equine encephalitis virus (WEEV) demonstrated that Bortezomib is a broad spectrum inhibitor of the New World alphaviruses. Time-of-addition assays showed that Bortezomib was an effective inhibitor of viral multiplication even when the drug was introduced many hours post exposure to the virus. Mass spectrometry analyses indicated that the VEEV capsid protein is ubiquitinated in infected cells, which was validated by confocal microscopy and immunoprecipitation assays. Subsequent studies revealed that capsid is ubiquitinated on K48 during early stages of infection which was affected by Bortezomib treatment. This study will aid future investigations in identifying host proteins as potential broad spectrum therapeutic targets for treating alphavirus infections. PMID:25927990

  12. The ubiquitin proteasome system plays a role in venezuelan equine encephalitis virus infection.

    PubMed

    Amaya, Moushimi; Keck, Forrest; Lindquist, Michael; Voss, Kelsey; Scavone, Lauren; Kehn-Hall, Kylene; Roberts, Brian; Bailey, Charles; Schmaljohn, Connie; Narayanan, Aarthi

    2015-01-01

    Many viruses have been implicated in utilizing or modulating the Ubiquitin Proteasome System (UPS) to enhance viral multiplication and/or to sustain a persistent infection. The mosquito-borne Venezuelan equine encephalitis virus (VEEV) belongs to the Togaviridae family and is an important biodefense pathogen and select agent. There are currently no approved vaccines or therapies for VEEV infections; therefore, it is imperative to identify novel targets for therapeutic development. We hypothesized that a functional UPS is required for efficient VEEV multiplication. We have shown that at non-toxic concentrations Bortezomib, a FDA-approved inhibitor of the proteasome, proved to be a potent inhibitor of VEEV multiplication in the human astrocytoma cell line U87MG. Bortezomib inhibited the virulent Trinidad donkey (TrD) strain and the attenuated TC-83 strain of VEEV. Additional studies with virulent strains of Eastern equine encephalitis virus (EEEV) and Western equine encephalitis virus (WEEV) demonstrated that Bortezomib is a broad spectrum inhibitor of the New World alphaviruses. Time-of-addition assays showed that Bortezomib was an effective inhibitor of viral multiplication even when the drug was introduced many hours post exposure to the virus. Mass spectrometry analyses indicated that the VEEV capsid protein is ubiquitinated in infected cells, which was validated by confocal microscopy and immunoprecipitation assays. Subsequent studies revealed that capsid is ubiquitinated on K48 during early stages of infection which was affected by Bortezomib treatment. This study will aid future investigations in identifying host proteins as potential broad spectrum therapeutic targets for treating alphavirus infections.

  13. Genetic and anatomic determinants of enzootic Venezuelan equine encephalitis virus infection of Culex (Melanoconion) taeniopus.

    PubMed

    Kenney, Joan L; Adams, A Paige; Gorchakov, Rodion; Leal, Grace; Weaver, Scott C

    2012-01-01

    Venezuelan equine encephalitis (VEE) is a re-emerging, mosquito-borne viral disease with the potential to cause fatal encephalitis in both humans and equids. Recently, detection of endemic VEE caused by enzootic strains has escalated in Mexico, Peru, Bolivia, Colombia and Ecuador, emphasizing the importance of understanding the enzootic transmission cycle of the etiologic agent, VEE virus (VEEV). The majority of work examining the viral determinants of vector infection has been performed in the epizootic mosquito vector, Aedes (Ochlerotatus) taeniorhynchus. Based on the fundamental differences between the epizootic and enzootic cycles, we hypothesized that the virus-vector interaction of the enzootic cycle is fundamentally different from that of the epizootic model. We therefore examined the determinants for VEEV IE infection in the enzootic vector, Culex (Melanoconion) taeniopus, and determined the number and susceptibility of midgut epithelial cells initially infected and their distribution compared to the epizootic virus-vector interaction. Using chimeric viruses, we demonstrated that the determinants of infection for the enzootic vector are different than those observed for the epizootic vector. Similarly, we showed that, unlike A. taeniorhynchus infection with subtype IC VEEV, C. taeniopus does not have a limited subpopulation of midgut cells susceptible to subtype IE VEEV. These findings support the hypothesis that the enzootic VEEV relationship with C. taeniopus differs from the epizootic virus-vector interaction in that the determinants appear to be found in both the nonstructural and structural regions, and initial midgut infection is not limited to a small population of susceptible cells.

  14. Altered mitochondrial dynamics as a consequence of Venezuelan Equine encephalitis virus infection.

    PubMed

    Keck, Forrest; Brooks-Faulconer, Taryn; Lark, Tyler; Ravishankar, Pavitra; Bailey, Charles; Salvador-Morales, Carolina; Narayanan, Aarthi

    2017-01-11

    Mitochondria are sentinel organelles that are impacted by various forms of cellular stress, including viral infections. While signaling events associated with mitochondria, including those activated by pathogen associated molecular patterns (PAMPs), are widely studied, alterations in mitochondrial distribution and changes in mitochondrial dynamics are also beginning to be associated with cellular insult. Cells of neuronal origin have been demonstrated to display remarkable alterations in several instances, including neurodegenerative disorders. Venezuelan Equine Encephalitis Virus (VEEV) is a New World alphavirus that infects neuronal cells and contributes to an encephalitic phenotype. We demonstrate that upon infection by the vaccine strain of VEEV (TC-83), astrocytoma cells experience a robust drop in mitochondrial activity, which corresponds with an increased accumulation of reactive oxygen species (ROS) in an infection-dependent manner. Infection status also corresponds with a prominent perinuclear accumulation of mitochondria. Cellular enzymatic machinery, including PINK1 and Parkin, appears to be enriched in mitochondrial fractions as compared with uninfected cells, which is indicative of mitochondrial damage. Dynamin related protein 1 (Drp1), a protein that is associated with mitochondrial fission, demonstrated a modest enrichment in mitochondrial fractions of infected cells. Treatment with an inhibitor of mitochondrial fission, Mdivi-1, led to a decrease in caspase cleavage, suggesting that mitochondrial fission was likely to contribute to apoptosis of infected cells. Finally, our data demonstrate that mitophagy ensues in infected cells. In combination, our data suggest that VEEV infection results in significant changes in the mitochondrial landscape that may influence pathological outcomes in the infected cell.

  15. Electron Tomography Analysis of Tick-Borne Encephalitis Virus Infection in Human Neurons.

    PubMed

    Bílý, Tomáš; Palus, Martin; Eyer, Luděk; Elsterová, Jana; Vancová, Marie; Růžek, Daniel

    2015-06-15

    Tick-borne encephalitis virus (TBEV) causes serious, potentially fatal neurological infections that affect humans in endemic regions of Europe and Asia. Neurons are the primary target for TBEV infection in the central nervous system. However, knowledge about this viral infection and virus-induced neuronal injury is fragmental. Here, we directly examined the pathology that occurs after TBEV infection in human primary neurons. We exploited the advantages of advanced high-pressure freezing and freeze-substitution techniques to achieve optimal preservation of infected cell architecture. Electron tomographic (ET) reconstructions elucidated high-resolution 3D images of the proliferating endoplasmic reticulum, and individual tubule-like structures of different diameters in the endoplasmic reticulum cisternae of single cells. ET revealed direct connections between the tubule-like structures and viral particles in the endoplasmic reticulum. Furthermore, ET showed connections between cellular microtubules and vacuoles that harbored the TBEV virions in neuronal extensions. This study was the first to characterize the 3D topographical organization of membranous whorls and autophagic vacuoles in TBEV-infected human neurons. The functional importance of autophagy during TBEV replication was studied in human neuroblastoma cells; stimulation of autophagy resulted in significantly increased dose-dependent TBEV production, whereas the inhibition of autophagy showed a profound, dose-dependent decrease of the yield of infectious virus.

  16. Cellular DDX3 regulates Japanese encephalitis virus replication by interacting with viral un-translated regions.

    PubMed

    Li, Chen; Ge, Ling-ling; Li, Peng-peng; Wang, Yue; Dai, Juan-juan; Sun, Ming-xia; Huang, Li; Shen, Zhi-qiang; Hu, Xiao-chun; Ishag, Hassan; Mao, Xiang

    2014-01-20

    Japanese encephalitis virus is one of the most common causes for epidemic viral encephalitis in humans and animals. Herein we demonstrated that cellular helicase DDX3 is involved in JEV replication. DDX3 knockdown inhibits JEV replication. The helicase activity of DDX3 is crucial for JEV replication. GST-pulldown and co-immunoprecipitation experiments demonstrated that DDX3 could interact with JEV non-structural proteins 3 and 5. Co-immunoprecipitation and confocal microscopy analysis confirmed that DDX3 interacts and colocalizes with these viral proteins and viral RNA during the infection. We determined that DDX3 binds to JEV 5' and 3' un-translated regions. We used a JEV-replicon system to demonstrate that DDX3 positively regulates viral RNA translation, which might affect viral RNA replication at the late stage of virus infection. Collectively, we identified that DDX3 is necessary for JEV infection, suggesting that DDX3 might be a novel target to design new antiviral agents against JEV or other flavivirus infections.

  17. 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

  18. Comparison of the efficacy of CO2-baited and unbaited light traps, gravid traps, backpack aspirators, and sweep net collections for sampling mosquitoes infected with Japanese encephalitis virus.

    PubMed

    Chen, Yu-Chen; Wang, Chih-Yuan; Teng, Hwa-Jen; Chen, Chien-Fu; Chang, Mi-Chun; Lu, Liang-Chen; Lin, Cheo; Jian, Shu-Wan; Wu, Ho-Sheng

    2011-06-01

    Two field studies were conducted to determine the efficacy of mosquito collection methods for species composition, species abundance, and Japanese encephalitis virus infection rates in Taiwan. Traps evaluated included John W. Hock (JH) model UD black light traps, JH model 1012 new standard miniature CDC light traps, JH model 1712 CDC gravid traps, and Taiwan-made Pest-O-Lite light traps. Backpack aspirators and sweep nets were also used to collect the resting population. Culex tritaeniorhynchus in all studies and Mansonia uniformis in the Taipei areas were the two most abundance species collected. Dry ice-baited UD black light traps were effective in regard to species diversity, species abundance, and Japanese encephalitis virus infection rates. The unbaited Pest-O-Lite light traps collected significantly more female mosquitoes than the UD black light traps but performed similarly with regard to species diversity and male mosquito collection. Most mosquitoes collected by Pest-O-Lite light traps were dried and not suitable for virus detection. Dry ice-baited CDC light traps collected significantly fewer mosquitoes than other light traps. Although CO(2) -baited UD black light traps with octenol attracted more mosquitoes, no statistical significance was found compared to CO(2) -baited UD black light traps without octenol. Japanese encephalitis viruses were isolated from half of the positive pools in UD black light traps and CDC light traps.

  19. Comparison of proteins specified by Murray Valley encephalitis, West Nile, Japanese encephalitis and St. Louis encephalitis viruses.

    PubMed

    Wright, P J; Warr, H M

    1986-10-01

    The relationships among proteins specified by Murray Valley encephalitis (MVE), West Nile (WN), Japanese encephalitis (JE) and St. Louis encephalitis (SLE) viruses were examined by peptide mapping. [3H]methionine-labelled tryptic peptides of viral proteins were separated by reverse phase high performance liquid chromatography (HPLC) and the separation profiles for a given protein specified by the different viruses were compared. Analyses of the non-structural protein NV5 (P98 or NS5) suggested that WN and SLE were the most closely related pair of viruses, and that JE was the virus most distant from the other three. Analyses of the structural proteins C and E failed to show the close relationship between WN and SLE indicated by the NV5 results, but did suggest that NV5 was the most conserved and E the least conserved of the three proteins.

  20. Control of Japanese encephalitis in Asia: the time is now

    PubMed Central

    Hills, Susan; Martin, Rebecca; Marfin, Anthony; Fischer, Marc

    2015-01-01

    Japanese encephalitis (JE) virus is the most common vaccine-preventable cause of encephalitis in Asia. Recent progress in the development and availability of improved JE vaccines has revitalized the prospects for JE control. There now are a number of safe and effective vaccines, two WHO prequalified vaccines available for pediatric use, at least one vaccine considered affordable for use in lower income countries, and a GAVI Alliance commitment to provide financial support to eligible countries for campaigns for children aged 9 months through 14 years. While challenges remain, this tremendous progress means there is a better opportunity than at any time in the past to prevent the substantial morbidity and mortality from this disease. PMID:24927959

  1. 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

  2. Ecological studies on the mosquito vectors of Japanese encephalitis

    PubMed Central

    Mitchell, C. J.; Chen, P. S.

    1973-01-01

    These studies were conducted in China (Province of Taiwan) to assess the populations of known and potential mosquito vectors of Japanese encephalitis in a typical endemic area, and to evaluate a variety of sampling techniques, some of which were new. Culex annulus was found to be the predominant vector species in the study area during the epidemic season; C. tritaeniorhynchus was never abundant, and C. fuscocephalus was rare. C. annulus and C. tritaeniorhynchus were active throughout the year, although populations were at a low level during the cool season. The results show that attention must be given to C. annulus as a possible vector where it is present in JE foci. The collection of mosquitos during the early evening hours from buffalo bait tethered outdoors was found to be the most efficient and sensitive means of monitoring vector populations throughout the year. During the JE epidemic season remarkable results were obtained with a vacuum sweep-net. PMID:4367779

  3. Crystal Structure of the Japanese Encephalitis Virus Envelope Protein

    SciTech Connect

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

    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 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.

  4. Japanese encephalitis virus tropism in experimentally infected pigs.

    PubMed

    Ricklin, Meret E; Garcìa-Nicolàs, Obdulio; Brechbühl, Daniel; Python, Sylvie; Zumkehr, Beatrice; Posthaus, Horst; Oevermann, Anna; Summerfield, Artur

    2016-02-24

    Pigs are considered to be the main amplifying host for Japanese encephalitis virus (JEV), and their infection can correlate with human cases of disease. Despite their importance in the ecology of the virus as it relates to human cases of encephalitis, the pathogenesis of JEV in pigs remains obscure. In the present study, the localization and kinetics of virus replication were investigated in various tissues after experimental intravenous infection of pigs. The data demonstrate a rapid and broad spreading of the virus to the central nervous system (CNS) and various other organs. A particular tropism of JEV in pigs not only to the CNS but also for secondary lymphoid tissue, in particular the tonsils with the overall highest viral loads, was observed. In this organ, even 11 days post infection, the latest time point of the experiment, no apparent decrease in viral RNA loads and live virus was found despite the presence of a neutralizing antibody response. This was also well beyond the clinical and viremic phase. These results are of significance for the pathogenesis of JEV, and call for further experimental studies focusing on the cellular source and duration of virus replication in pigs.

  5. E3 Ubiquitin Ligase Nedd4 Promotes Japanese Encephalitis Virus Replication by Suppressing Autophagy in Human Neuroblastoma Cells.

    PubMed

    Xu, Qingqiang; Zhu, Naiwei; Chen, Shenglin; Zhao, Ping; Ren, Hao; Zhu, Shiying; Tang, Hailin; Zhu, Yongzhe; Qi, Zhongtian

    2017-03-28

    Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus that causes the most prevalent viral encephalitis in Asia. Since JEV is a neurotropic virus, it is important to identify key molecules that mediate JEV infection in neuronal cells and to investigate their underlying mechanisms. In this study, the critical role of Nedd4, an E3 ubiquitin ligase that is highly expressed in the central nervous system, was examined in JEV propagation. In SK-N-SH neuroblastoma cells, Nedd4 was up-regulated in response to JEV infection. Moreover, down-regulation of Nedd4 resulted in a significant decrease in JEV replication without alterations in virus attachment and internalization or in JEV pseudotyped virus infection, suggesting that Nedd4 participates in the replication but not in the entry stage of JEV infection. Further functional analysis showed that Nedd4 attenuated JEV-induced autophagy, which negatively regulates virus replication during infection. These results suggest that Nedd4 facilitates the replication of JEV by suppressing virus-induced autophagy. Taken together, our results indicate that Nedd4 plays a crucial role in JEV infection of neuronal cells, which provides a potential target for the development of novel treatment to combat JEV infection.

  6. E3 Ubiquitin Ligase Nedd4 Promotes Japanese Encephalitis Virus Replication by Suppressing Autophagy in Human Neuroblastoma Cells

    PubMed Central

    Xu, Qingqiang; Zhu, Naiwei; Chen, Shenglin; Zhao, Ping; Ren, Hao; Zhu, Shiying; Tang, Hailin; Zhu, Yongzhe; Qi, Zhongtian

    2017-01-01

    Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus that causes the most prevalent viral encephalitis in Asia. Since JEV is a neurotropic virus, it is important to identify key molecules that mediate JEV infection in neuronal cells and to investigate their underlying mechanisms. In this study, the critical role of Nedd4, an E3 ubiquitin ligase that is highly expressed in the central nervous system, was examined in JEV propagation. In SK-N-SH neuroblastoma cells, Nedd4 was up-regulated in response to JEV infection. Moreover, down-regulation of Nedd4 resulted in a significant decrease in JEV replication without alterations in virus attachment and internalization or in JEV pseudotyped virus infection, suggesting that Nedd4 participates in the replication but not in the entry stage of JEV infection. Further functional analysis showed that Nedd4 attenuated JEV-induced autophagy, which negatively regulates virus replication during infection. These results suggest that Nedd4 facilitates the replication of JEV by suppressing virus-induced autophagy. Taken together, our results indicate that Nedd4 plays a crucial role in JEV infection of neuronal cells, which provides a potential target for the development of novel treatment to combat JEV infection. PMID:28349961

  7. 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

  8. Regional Impact of Climate on Japanese Encephalitis in Areas Located near the Three Gorges Dam

    PubMed Central

    Mao, Deqiang; Luo, Chao; He, Yuanyuan; Liang, Guodong; Lu, Bo; Bisesi, Michael S.; Sun, Qinghua; Xu, Xinyi; Yang, Weizhong; Liu, Qiyong

    2014-01-01

    Background In this study, we aim to identify key climatic factors that are associated with the transmission of Japanese encephalitis virus in areas located near the Three Gorges Dam, between 1997 and 2008. Methods We identified three geographical regions of Chongqing, based on their distance from the Three Gorges Dam. Collectively, the three regions consisted of 12 districts from which study information was collected. Zero-Inflated Poisson Regression models were run to identify key climatic factors of the transmission of Japanese encephalitis virus for both the whole study area and for each individual region; linear regression models were conducted to examine the fluctuation of climatic variables over time during the construction of the Three Gorges Dam. Results Between 1997 and 2008, the incidence of Japanese encephalitis decreased throughout the entire city of Chongqing, with noticeable variations taking place in 2000, 2001 and 2006. The eastern region, which is closest to the Three Gorges Dam, suffered the highest incidence of Japanese encephalitis, while the western region experienced the lowest incidence. Linear regression models revealed that there were seasonal fluctuations of climatic variables during this period. Zero-Inflated Poisson Regression models indicated a significant positive association between temperature (with a lag of 1 and 3 months) and Japanese encephalitis incidence, and a significant negative association between rainfall (with a lag of 0 and 4 months) and Japanese encephalitis incidence. Conclusion The spatial and temporal trends of Japanese encephalitis incidence that occurred in the City of Chongqing were associated with temperature and rainfall. Seasonal fluctuations of climatic variables during this period were also observed. Additional studies that focus on long-term data collection are needed to validate the findings of this study and to further explore the effects of the Three Gorges Dam on Japanese encephalitis and other related

  9. Primary viraemia responses of herons to experimental infection with Murray Valley encephalitis, Kunjin and Japanese encephalitis viruses.

    PubMed

    Boyle, D B; Dickerman, R W; Marshall, I D

    1983-12-01

    Rufous night herons, Pacific herons, little egrets and intermediate egrets were experimentally infected with Murray Valley encephalitis, Kunjin or Japanese encephalitis viruses. Viraemias of at least one day's duration were detected in all birds except two intermediate egrets inoculated with a very low dose of Kunjin virus and one rufous night heron inoculated with Japanese encephalitis virus. there was usually a viraemia of 3 to 5 days' duration commencing on the first or second day and continuing until day 5 or 6 and rarely until day 7. Maximum titres tended to be higher in young birds, up to 2-5 months of age (10(4)-10(5) mouse LD50/ml), than in older birds more than 8 months of age (10(3)-10(4) mouse LD50/ml). Significant differences in maximum viraemia titres were not observed in the different species or between Murray Valley encephalitis and Kunjin viruses. Japanese encephalitis viraemias were significantly lower, but this was probably due to the high mouse brain passage level of the strain used. The onset of viraemia was earlier in intermediate egrets than in rufous night herons inoculated with similar doses of Murray Valley encephalitis virus, but no difference in the susceptibility to infection was observed. With Kunjin virus there was a significant difference in the susceptibility of intermediate egrets and rufous night herons, with rufous night herons being more susceptible to infection with low doses of virus. This difference in threshold of infection, if it extends to other species with both Kunjin and Murray Valley encephalitis viruses, may, in part, be an explanation for the greater incidence of natural infections observed in rufous night herons compared with other species and orders of water birds.

  10. Perivascular inflammatory cells in ovine Visna/maedi encephalitis and their possible role in virus infection and lesion progression.

    PubMed

    Polledo, Laura; González, Jorge; Benavides, Julio; Martínez-Fernández, Beatriz; Ferreras, Ma Carmen; Marín, Juan F García

    2012-12-01

    We examined the distribution in the perivascular spaces of Visna/maedi antigen, T cells (CD3+, CD4+ and CD8+), B cells and macrophages by immunohistochemistry in 22 natural cases of Visna/maedi encephalitis. Sheep showed lymphocytic or histiocytic lesions. In mild lymphocytic lesions, the viral antigen was detected in perivascular cuffs where CD8+ T cells predominated, but in severe lymphocytic lesions, sparse antigen was identified, and CD8+/CD4+ T cells appeared in a similar proportion in multilayer perivascular sleeves. In histiocytic lesions, vessels were surrounded by macrophages with abundant viral antigen, with CD8+/CD4+ T cells and B cells in the periphery. These results could reflect different stages of virus neuroinvasion and clarify the neuropathogenesis of Visna/maedi encephalitis.

  11. 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.

  12. St. Louis Encephalitis

    MedlinePlus

    ... Fact Sheet Other diseases transmitted by mosquitoes Chikungunya virus Dengue Eastern Equine Encephalitis Japanese Encephalitis Malaria La Crosse Encephalitis Western Equine Encephalitis West Nile virus Yellow Fever Saint Louis Encephalitis Frequently Asked Questions ...

  13. Specificity and Dynamics of Effector and Memory CD8 T Cell Responses in Human Tick-Borne Encephalitis Virus Infection

    PubMed Central

    Blom, Kim; Braun, Monika; Pakalniene, Jolita; Dailidyte, Laura; Béziat, Vivien; Lampen, Margit H.; Klingström, Jonas; Lagerqvist, Nina; Kjerstadius, Torbjörn; Michaëlsson, Jakob; Lindquist, Lars; Ljunggren, Hans-Gustaf; Sandberg, Johan K.; Mickiene, Aukse; Gredmark-Russ, Sara

    2015-01-01

    Tick-borne encephalitis virus (TBEV) is transferred to humans by ticks. The virus causes tick-borne encephalitis (TBE) with symptoms such as meningitis and meningoencephalitis. About one third of the patients suffer from long-lasting sequelae after clearance of the infection. Studies of the immune response during TBEV-infection are essential to the understanding of host responses to TBEV-infection and for the development of therapeutics. Here, we studied in detail the primary CD8 T cell response to TBEV in patients with acute TBE. Peripheral blood CD8 T cells mounted a considerable response to TBEV-infection as assessed by Ki67 and CD38 co-expression. These activated cells showed a CD45RA-CCR7-CD127- phenotype at day 7 after hospitalization, phenotypically defining them as effector cells. An immunodominant HLA-A2-restricted TBEV epitope was identified and utilized to study the characteristics and temporal dynamics of the antigen-specific response. The functional profile of TBEV-specific CD8 T cells was dominated by variants of mono-functional cells as the effector response matured. Antigen-specific CD8 T cells predominantly displayed a distinct Eomes+Ki67+T-bet+ effector phenotype at the peak of the response, which transitioned to an Eomes-Ki67-T-bet+ phenotype as the infection resolved and memory was established. These transcription factors thus characterize and discriminate stages of the antigen-specific T cell response during acute TBEV-infection. Altogether, CD8 T cells responded strongly to acute TBEV infection and passed through an effector phase, prior to gradual differentiation into memory cells with distinct transcription factor expression-patterns throughout the different phases. PMID:25611738

  14. Post-marketing surveillance of live-attenuated Japanese encephalitis vaccine safety in China.

    PubMed

    Wang, Yali; Dong, Duo; Cheng, Gang; Zuo, Shuyan; Liu, Dawei; Du, Xiaoxi

    2014-10-07

    Japanese encephalitis (JE) is the most severe form of viral encephalitis in Asia and no specific treatment is available. Vaccination provides an effective intervention to prevent JE. In this paper, surveillance data for adverse events following immunization (AEFI) related to SA-14-14-2 live-attenuated Japanese encephalitis vaccine (Chengdu Institute of Biological Products) was presented. This information has been routinely generated by the Chinese national surveillance system for the period 2009-2012. There were 6024 AEFI cases (estimated reported rate 96.55 per million doses). Most common symptoms of adverse events were fever, redness, induration and skin rash. There were 70 serious AEFI cases (1.12 per million doses), including 9 cases of meningoencephalitis and 4 cases of death. The post-marketing surveillance data add the evidence that the Chengdu institute live attenutated vaccine has a reasonable safety profile. The relationship between encephalitis and SA-14-14-2 vaccination should be further studied.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  16. Epidemio-entomological survey of Japanese encephalitis in Korea.

    PubMed

    Baik, D H; Joo, C Y

    1991-03-01

    In order to determine the seasonal prevalence and population dynamics of Culex tritaeniorhynchus in relation to the epidemics of Japanese encephalitis, and ecology of these vector mosquito in Kyungpook Province, Korea, studies were conducted during the period of 7 years from 1984 to 1990. Cx. tritaeniorhynchus first collected in June between 4th and 28th, and trapped in large numbers during the period from mid-August to early September, showed a simple sharply pointed one-peaked curve. There was a gradual decrease from mid-September, with a very small number of them collected until early October in every year. The average number of Cx. tritaeniorhynchus rapidly decreased after 1985, and the number became particularly low in 1989. The highest population density, which was observed in August during the initial three years, was found to be delayed in the following years, accompanied by a decrease in the number of mosquitoes. In the trend of nocturnal activity of Cx. tritaeniorhynchus, with oncoming darkness they become very active, gradually decreasing in activity toward mid night, but slightly increasing toward dawn. The immature stages of Cx. tritaeniorhynchus were first found in rice fields contributing to peak adult densities in mid-July. The highest average densities of Cx. tritaeniorhynchus was 14,900 per m2 on mid-August 19th. The larval Cx. tritaeniorhynchus showed high resistance levels and resistance ratios against 5 organophosphorus compounds. In the adult horizontal life table characteristics of Kyungsan colonies of Cx. tritaeniorhynchus under insectary conditions, life expectancy was 28.3 days for males and 59.8 days for females. The net reproductive rate was 7.8 and generation time was 25.6 days.

  17. Estimated global incidence of Japanese encephalitis: a systematic review

    PubMed Central

    Campbell, Grant L; Hills, Susan L; Fischer, Marc; Jacobson, Julie A; Hoke, Charles H; Hombach, Joachim M; Marfin, Anthony A; Solomon, Tom; Tsai, Theodore F; Tsu, Vivien D

    2011-01-01

    Abstract Objective To update the estimated global incidence of Japanese encephalitis (JE) using recent data for the purpose of guiding prevention and control efforts. Methods Thirty-two areas endemic for JE in 24 Asian and Western Pacific countries were sorted into 10 incidence groups on the basis of published data and expert opinion. Population-based surveillance studies using laboratory-confirmed cases were sought for each incidence group by a computerized search of the scientific literature. When no eligible studies existed for a particular incidence group, incidence data were extrapolated from related groups. Findings A total of 12 eligible studies representing 7 of 10 incidence groups in 24 JE-endemic countries were identified. Approximately 67 900 JE cases typically occur annually (overall incidence: 1.8 per 100 000), of which only about 10% are reported to the World Health Organization. Approximately 33 900 (50%) of these cases occur in China (excluding Taiwan) and approximately 51 000 (75%) occur in children aged 0–14 years (incidence: 5.4 per 100 000). Approximately 55 000 (81%) cases occur in areas with well established or developing JE vaccination programmes, while approximately 12 900 (19%) occur in areas with minimal or no JE vaccination programmes. Conclusion Recent data allowed us to refine the estimate of the global incidence of JE, which remains substantial despite improvements in vaccination coverage. More and better incidence studies in selected countries, particularly China and India, are needed to further refine these estimates. PMID:22084515

  18. Immunogenicity of single-dose Vero cell-derived Japanese encephalitis vaccine in Japanese adults.

    PubMed

    Takeshita, Nozomi; Lim, Chang-Kweng; Mizuno, Yasutaka; Shimbo, Takuro; Kotaki, Akira; Ujiie, Mugen; Hayakawa, Kayoko; Kato, Yasuyuki; Kanagawa, Shuzo; Kaku, Mitsuo; Takasaki, Tomohiko

    2014-04-01

    In Japan, intensive immunization against Japanese encephalitis (JE) was performed from 1967 to 1976, and regular JE immunization was performed thereafter. However, for Japanese adults facing JE risk, dates of vaccination with new inactivated Vero cell-derived JE vaccine are unavailable. This study investigated how a single dose of Vero cell-derived JE vaccine affects Japanese adults. Neutralizing antibodies were measured pre- and post-JE vaccination in 79 participants (age 40.7 ± 9.4 years), enrolled between October 2009 and March 2011, whose JE-vaccination data were gathered from vaccination records and history taking. Before vaccination, the participants' seroprotection rate (SPR) was 51.9%, whereas SPR after vaccination was 93.7%. The seroconversion rate (SCR), which measures seronegative cases that turn seropositive after vaccination, was 86.8%. The geometric mean titer (GMT) was 14.7 before vaccination and 70.1 after vaccination. Age was a significant difference between seroprotected (42.8 years) and non-seroprotected (38.7 years) groups before vaccination. Then the difference of age, SCR, pre-vaccination GMT, post-vaccination GMT and sex ratio were also significant in participants aged 25-39 years and ≥40 years, who represent generations born when Japan's JE-vaccination policy changed. SCR was 100% in participants aged 25-39 years with a vaccination recorded 55.6% in participants aged 25-39 without a vaccination record, and 96.0% in participants aged ≥40 years. Thus, more participants aged 25-39 years were seroprotected before vaccination, but SCR was higher in those aged ≥40 years. Most Japanese adults can be protected after one-dose vaccination, but this may be insufficient for people aged 25-39 years without recorded JE vaccination.

  19. A spatial and temporal analysis of Japanese encephalitis in mainland China, 1963-1975: a period without Japanese encephalitis vaccination.

    PubMed

    Li, Xiaolong; Gao, Xiaoyan; Ren, Zhoupeng; Cao, Yuxi; Wang, Jinfeng; Liang, Guodong

    2014-01-01

    More than a million Japanese encephalitis (JE) cases occurred in mainland China from the 1960s to 1970s without vaccine interventions. The aim of this study is to analyze the spatial and temporal pattern of JE cases reported in mainland China from 1965 to 1973 in the absence of JE vaccination, and to discuss the impacts of climatic and geographical factors on JE during that period. Thus, the data of reported JE cases at provincial level and monthly precipitation and monthly mean temperature from 1963 to 1975 in mainland China were collected. Local Indicators of Spatial Association analysis was performed to identify spatial clusters at the province level. During that period, The epidemic peaked in 1966 and 1971 and the JE incidence reached up to 20.58/100000 and 20.92/100000, respectively. The endemic regions can be divided into three classes including high, medium, and low prevalence regions. Through spatial cluster analysis, JE epidemic hot spots were identified; most were located in the Yangtze River Plain which lies in the southeast of China. In addition, JE incidence was shown to vary among eight geomorphic units in China. Also, the JE incidence in the Loess Plateau and the North China Plain was showed to increase with the rise of temperature. Likewise, JE incidence in the Loess Plateau and the Yangtze River Plain was observed a same trend with the increase of rainfall. In conclusion, the JE cases clustered geographically during the epidemic period. Besides, the JE incidence was markedly higher on the plains than plateaus. These results may provide an insight into the epidemiological characteristics of JE in the absence of vaccine interventions and assist health authorities, both in China and potentially in Europe and Americas, in JE prevention and control strategies.

  20. The blood-brain barrier in the cerebrum is the initial site for the Japanese encephalitis virus entering the central nervous system.

    PubMed

    Liu, Tsan-Hsiun; Liang, Li-Ching; Wang, Chien-Chih; Liu, Huei-Chung; Chen, Wei-June

    2008-11-01

    Japanese encephalitis (JE) virus is a member of the encephalitic flaviviruses and frequently causes neurological sequelae in a proportion of patients who survive the acute phase of the infection. In the present study, we molecularly identified viral infection in the brain of mice with rigidity of hindlimbs and/or abnormal gait, in which JE virus particles appeared within membrane-bound vacuoles of neurons throughout the central nervous system. Deformation of tight junctions (TJs) shown as dissociation of endothelial cells in capillaries, implying that the integrity of the blood-brain barrier (BBB) has been compromised by JE virus infection. BBB permeability evidently increased in the cerebrum, but not in the cerebellum, of JE virus-infected mice intravenously injected with the tracer of Evans blue dye. This suggests that the permeability of the BBB differentially changed in response to viral infection, leading to the entry of JE virions and/or putatively infected leukocytes from the periphery to the cerebrum as the initial site of infection in the central nervous system (CNS). Theoretically, the virus spread to the cerebellum soon after the cerebrum became infected.

  1. Susceptibility of a North American Culex quinquefasciatus to Japanese encephalitis virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  2. 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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  4. The first report on human cases serologically diagnosed as Japanese encephalitis in Indonesia.

    PubMed

    Yoshida, M; Igarashi, A; Suwendra, P; Inada, K; Maha, M S; Kari, K; Suda, H; Antonio, M T; Arhana, B N; Takikawa, Y; Maesawa, S; Yoshida, H; Chiba, M

    1999-12-01

    Although Japanese encephalitis (JE) virus was isolated from mosquitos in 1974, human JE cases have never been reported in Indonesia in spite of the prevalence of anti-JE antibodies among human and pig populations as well as abundant JE vector mosquitos. In this report, we describe serological diagnosis of JE cases in Bali. Indonesia. using IgM-capture ELISA both on serum and cerebrospinal fluid (CSF) of the patients. In the first series of our investigation (Series 1), we examined serum specimens from 12 patients with clinical diagnosis of viral encephalitis, meningitis or dengue hemorrhagic fever (DHF), and found 2 possible JE cases. In the next series (Series 2), we examined both serum and CSF from encephalitis patients and gave laboratory diagnosis of JE. One of them was suspected to have concomitant or recent infection with dengue virus, probably type 3. These results strongly indicated that JE has been prevalent in Bali, Indonesia.

  5. Immunogenicity and safety of currently available Japanese encephalitis vaccines: A systematic review

    PubMed Central

    Li, Xing; Ma, Shu-Juan; Liu, Xie; Jiang, Li-Na; Zhou, Jun-Hua; Xiong, Yi-Quan; Ding, Hong; Chen, Qing

    2015-01-01

    A number of Japanese encephalitis (JE) vaccines have been used for preventing Japanese encephalitis around the world. We here reviewed the immunogenicity and safety of the currently available Japanese encephalitis vaccines. We searched Pubmed, Embase, Web of Science, the Cochrane Library and other online databases up to March 25, 2014 for studies focusing on currently used JE vaccines in any language. The primary outcomes were the seroconversion rate against JEV and adverse events. Meta-analysis was performed for the primary outcome when available. A total of 51 articles were included. Studies were grouped on the basic types of vaccines. This systematic review led to 2 aspects of the conclusions. On one hand, all the currently available JE vaccines are safe and effective. On the other hand, the overall of JE vaccine evaluation is disorganized, the large variation in study designs, vaccine types, schedules, doses, population and few hand-to-hand trails, make direct comparisons difficult. In order to make a more evidence-based decision on optimizing the JE vaccine, it is warranted to standardize the JE vaccine evaluation research. PMID:25668666

  6. 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.

  7. Vector-free transmission and persistence of Japanese encephalitis virus in pigs

    PubMed Central

    Ricklin, Meret E.; García-Nicolás, Obdulio; Brechbühl, Daniel; Python, Sylvie; Zumkehr, Beatrice; Nougairede, Antoine; Charrel, Remi N.; Posthaus, Horst; Oevermann, Anna; Summerfield, Artur

    2016-01-01

    Japanese encephalitis virus (JEV), a main cause of severe viral encephalitis in humans, has a complex ecology, composed of a cycle involving primarily waterbirds and mosquitoes, as well as a cycle involving pigs as amplifying hosts. To date, JEV transmission has been exclusively described as being mosquito-mediated. Here we demonstrate that JEV can be transmitted between pigs in the absence of arthropod vectors. Pigs shed virus in oronasal secretions and are highly susceptible to oronasal infection. Clinical symptoms, virus tropism and central nervous system histological lesions are similar in pigs infected through needle, contact or oronasal inoculation. In all cases, a particularly important site of replication are the tonsils, in which JEV is found to persist for at least 25 days despite the presence of high levels of neutralizing antibodies. Our findings could have a major impact on the ecology of JEV in temperate regions with short mosquito seasons. PMID:26902924

  8. 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.

  9. The NS3 and NS4A genes as the targets of RNA interference inhibit replication of Japanese encephalitis virus in vitro and in vivo.

    PubMed

    Yuan, Lei; Wu, Rui; Liu, Hanyang; Wen, Xintian; Huang, Xiaobo; Wen, Yiping; Ma, Xiaoping; Yan, Qigui; Huang, Yong; Zhao, Qin; Cao, Sanjie

    2016-12-15

    Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus that can cause acute encephalitis with a high fatality rate. RNA interference (RNAi) is a powerful tool to silence gene expression and a potential therapy for virus infection. In this study, the antiviral ability of eight shRNA expression plasmids targeting different sites of the NS3 and NS4A genes of JEV was determined in BHK21 cells and mice. The pGP-NS3-3 and pGP-NS4A-4 suppressed 93.9% and 82.0% of JEV mRNA in cells, respectively. The virus titer in cells was reduced approximately 950-fold by pretreating with pGP-NS3-4, and 640-fold by pretreating with pGP-NS4A-4. The results of western blot and immunofluorescence analysis showed JEV E protein and viral load in cells were remarkably inhibited by shRNA expression plasmids. The viral load in brains of mice pretreated with pGP-NS3-4 or pGP-NS4A-4 were reduced approximately 2400-fold and 800-fold, respectively, and the survival rate of mice challenged with JEV were 70% and 50%, respectively. However, the antiviral ability of shRNA expression plasmids was decreased over time. This study indicates that RNAi targeting of the NS3 and NS4A genes of JEV can sufficiently inhibit the replication of JEV in vitro and in vivo, and NS3 and NS4A genes might be potential targets of molecular therapy for JEV infection.

  10. A monoclonal antibody against PrM/M protein of Japanese encephalitis virus.

    PubMed

    Hua, Rong-Hong; Bu, Zhi-Gao

    2011-10-01

    Japanese encephalitis virus (JEV) is a major public health threat in the Asia-Pacific region. The pre-membrane (PrM) protein of Japanese encephalitis virus is cleaved during maturation by the cellular protease into the structural protein M and a pr-segment. Here, we describe a procedure to generate monoclonal antibody (MAb) against JEV PrM/M protein and investigate its characteristics. Western blot analysis showed that the MAbs produced in this study were against JEV PrM/M specifically. Indirect immunofluorescence assay demonstrated that they could recognize native PrM/M protein in JEV-infected BHK-21 cells. Preliminary studies identified the epitope of the MAb with a set of synthesized overlapping peptides covering the whole length of PrM protein of JEV. The MAbs reported here may provide valuable tools for the further exploration of biological properties and functions of PrM/M protein and may also be developed for potential clinical applications.

  11. European Aedes albopictus and Culex pipiens Are Competent Vectors for Japanese Encephalitis Virus

    PubMed Central

    Desprès, Philippe

    2017-01-01

    Background Japanese encephalitis virus (JEV) is the causative agent of Japanese encephalitis, the leading cause of viral encephalitis in Asia. JEV transmission cycle involves mosquitoes and vertebrate hosts. The detection of JEV RNA in a pool of Culex pipiens caught in 2010 in Italy raised the concern of a putative emergence of the virus in Europe. We aimed to study the vector competence of European mosquito populations, such as Cx. pipiens and Aedes albopictus for JEV genotypes 3 and 5. Findings After oral feeding on an infectious blood meal, mosquitoes were dissected at various times post-virus exposure. We found that the peak for JEV infection and transmission was between 11 and 13 days post-virus exposure. We observed a faster dissemination of both JEV genotypes in Ae. albopictus mosquitoes, when compared with Cx. pipiens mosquitoes. We also dissected salivary glands and collected saliva from infected mosquitoes and showed that Ae. albopictus mosquitoes transmitted JEV earlier than Cx. pipiens. The virus collected from Ae. albopictus and Cx. pipiens saliva was competent at causing pathogenesis in a mouse model for JEV infection. Using this model, we found that mosquito saliva or salivary glands did not enhance the severity of the disease. Conclusions In this study, we demonstrated that European populations of Ae. albopictus and Cx. pipiens were efficient vectors for JEV transmission. Susceptible vertebrate species that develop high viremia are an obligatory part of the JEV transmission cycle. This study highlights the need to investigate the susceptibility of potential JEV reservoir hosts in Europe, notably amongst swine populations and local water birds. PMID:28085881

  12. Review of climate, landscape, and viral genetics as drivers of the Japanese encephalitis virus ecology.

    PubMed

    Le Flohic, Guillaume; Porphyre, Vincent; Barbazan, Philippe; Gonzalez, Jean-Paul

    2013-01-01

    The Japanese encephalitis virus (JEV), an arthropod-born Flavivirus, is the major cause of viral encephalitis, responsible for 10,000-15,000 deaths each year, yet is a neglected tropical disease. Since the JEV distribution area has been large and continuously extending toward new Asian and Australasian regions, it is considered an emerging and reemerging pathogen. Despite large effective immunization campaigns, Japanese encephalitis remains a disease of global health concern. JEV zoonotic transmission cycles may be either wild or domestic: the first involves wading birds as wild amplifying hosts; the second involves pigs as the main domestic amplifying hosts. Culex mosquito species, especially Cx. tritaeniorhynchus, are the main competent vectors. Although five JEV genotypes circulate, neither clear-cut genotype-phenotype relationship nor clear variations in genotype fitness to hosts or vectors have been identified. Instead, the molecular epidemiology appears highly dependent on vectors, hosts' biology, and on a set of environmental factors. At global scale, climate, land cover, and land use, otherwise strongly dependent on human activities, affect the abundance of JEV vectors, and of wild and domestic hosts. Chiefly, the increase of rice-cultivated surface, intensively used by wading birds, and of pig production in Asia has provided a high availability of resources to mosquito vectors, enhancing the JEV maintenance, amplification, and transmission. At fine scale, the characteristics (density, size, spatial arrangement) of three landscape elements (paddy fields, pig farms, human habitations) facilitate or impede movement of vectors, then determine how the JEV interacts with hosts and vectors and ultimately the infection risk to humans. If the JEV is introduced in a favorable landscape, either by live infected animals or by vectors, then the virus can emerge and become a major threat for human health. Multidisciplinary research is essential to shed light on the

  13. An outbreak of VHSV (viral hemorrhagic septicemia virus) infection in farmed Japanese flounder Paralichthys olivaceus in Japan.

    PubMed

    Isshik, T; Nishizawa, T; Kobayashi, T; Nagano, T; Miyazaki, T

    2001-11-08

    A rhabdoviral disease occurred in farmed populations of market sized Japanese flounder (hirame) Paralichthys olivaceus in the Seto Inland Sea of Japan in 1996. The causative agent was identified as viral hemorrhagic septicemia virus (VHSV) based on morphological, immunological, and genetic analyses. Diseased fish that were artificially injected with a representative virus isolate showed the same pathological signs and high mortality as observed in the natural outbreak. This is the first report of an outbreak of VHSV infection in cultured fish in Japan. Clinical signs of diseased fish included dark body coloration, an expanded abdomen due to ascites, congested liver, splenomegaly, and a swollen kidney. Myocardial necrosis was most prominent and accompanied by inflammatory reactions. Necrotic lesions also occurred in the liver, spleen and hematopoietic tissue, and were accompanied by circulatory disturbances due to cardiac failure. Hemorrhagic lesions did not always appear in the lateral musculature. Transmission electron microscopy revealed many rhabdovirus particles and associated inclusion bodies containing nucleocapsids in the necrotized myocardium. The histopathological findings indicated that the necrotizing myocarditis could be considered a pathognomonic sign of VHSV infection in Japanese flounder.

  14. First Complete Genome Sequence of Genotype III Japanese Encephalitis Virus Isolated from a Stillborn Piglet in India

    PubMed Central

    Desingu, P. A.; Ray, Pradeep K.; John, Jeny K.; Das, T.; Dubal, Z. B.; Rajak, K. K.; Singh, R. K.

    2017-01-01

    ABSTRACT We report here the first complete genome of the Japanese encephalitis virus (JEV) genotype III strain JEV/SW/IVRI/395A/2014, isolated from stillborn piglets in India. It shares 99% identity with strain JaOArS982 and a few other strains from Japan. PMID:28104663

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  16. Incidence and clinical features of herpes simplex viruses (1 and 2) and varicella-zoster virus infections in an adult Korean population with aseptic meningitis or encephalitis.

    PubMed

    Choi, Rihwa; Kim, Gyeong-Moon; Jo, Ik Joon; Sim, Min Seob; Song, Keun Jeong; Kim, Byoung Joon; Na, Duk L; Huh, Hee Jae; Kim, Jong-Won; Ki, Chang-Seok; Lee, Nam Yong

    2014-06-01

    Since there are limited data on the incidence and clinical findings of central nervous system (CNS) infection by three α-herpesviruses including human herpes simplex virus 1 (HSV-1), HSV-2 and varicella-zoster virus (VZV) in Korea, a retrospective analysis of clinical data and polymerase chain reaction (PCR) results was performed in patients who presented with suspicion of acute viral meningitis and/or encephalitis at the emergency department of a tertiary referral hospital in Seoul, Korea. During the 3-year study period, a total of 224 cerebrospinal fluid (CSF) samples from 224 patients were examined. Among the 224 patients, 135 (60.3%) patients were identified as having aseptic meningitis (n = 70, 51.9%), encephalitis (n = 41, 30.4%) or meningoencephalitis (n = 24, 17.8%) at discharge. Twenty-four (17.8%) patients were identified as having VZV meningitis (n = 16, 11.9%), VZV meningoencephalitis (n = 2, 1.5%), HSV-2 meningitis (n = 4, 3.0%), or HSV-1 encephalitis (n = 2, 1.5%). Of the 24 patients infected with the three herpesviruses, immunocompromised patients accounted for 33.3% (n = 8). Skin rashes were observed in half (n = 9) of the patients with VZV, and none with HSV-1 or HSV-2. One patient with VZV meningitis and four patients with brain parenchymal involvement had neurologic sequelae. In conclusion, three herpesviruses are important causative agents of CNS infectious disease with significant morbidity in adults, regardless of the immunologic status. Therefore, CSF should be examined for HSV-1, HSV-2, and VZV using sensitive diagnostic methods in all cases of adult patients with clinical manifestations of CNS disease in order to identify the correct etiology and to determine appropriate therapy.

  17. Neonatal case of herpes simplex virus encephalitis after delivery from a woman whose genital herpes simplex virus infection had been treated with acyclovir.

    PubMed

    Kumasaka, Sakae; Takagi, Atsushi; Kuwabara, Kentaro; Migita, Makoto

    2013-01-01

    A case of herpes simplex virus (HSV) encephalitis in a neonate after delivery from a woman whose genital HSV infection had been treated with acyclovir is reported. The main approach to prevent genital HSV infection in the neonate is interruption of transmission at the time of delivery. Guidelines for prophylactic therapy with acyclovir have been established, but the risk of neonatal infection remains. A fever began to develop in a male neonate delivered vaginally from a 35-year-old woman. Treatment with intravenous acyclovir was started on the basis of a diagnosis of HSV encephalitis, because polymerase chain reaction was positive for HSV in the cerebrospinal fluid. The mother had had a first genital HSV infection during the second trimester, but treatment with injected acyclovir had caused the blisters and erosion to resolve by the time of delivery. Important steps for preventing neonatal HSV infection are the appropriate treatment of mothers with a history of genital HSV infection, the assessment of delivery methods, and the appropriate treatment of neonates.

  18. Failure of mefloquine therapy in progressive multifocal leukoencephalopathy: report of two Japanese patients without human immunodeficiency virus infection.

    PubMed

    Kobayashi, Zen; Akaza, Miho; Numasawa, Yoshiyuki; Ishihara, Shoichiro; Tomimitsu, Hiroyuki; Nakamichi, Kazuo; Saijo, Masayuki; Morio, Tomohiro; Shimizu, Norio; Sanjo, Nobuo; Shintani, Shuzo; Mizusawa, Hidehiro

    2013-01-15

    Although progressive multifocal leukoencephalopathy (PML) cases showing responses to mefloquine therapy have been reported, the efficacy of mefloquine for PML remains unclear. We report on the failure of mefloquine therapy in two Japanese patients with PML unrelated to human immunodeficiency virus. One of the patients was a 47-year-old male who had been treated with chemotherapy for Waldenström macroglobulinemia, and the other was an 81-year-old male with idiopathic CD4(+) lymphocytopenia. Diagnosis of PML was established based on MRI findings and increased JC virus DNA in the cerebrospinal fluid in both patients. Mefloquine was initiated about 5 months and 2 months after the onset of PML, respectively. During mefloquine therapy, clinical and radiological progression was observed, and JC virus DNA in the cerebrospinal fluid was increased in both patients. Both patients died about 4 months and 2 months after initiation of mefloquine, respectively. Further studies are necessary to clarify the differences between mefloquine responders and non-responders in PML.

  19. Dengue virus and Japanese encephalitis virus epidemiological shifts in Nepal: a case of opposing trends.

    PubMed

    Dumre, Shyam P; Shakya, Geeta; Na-Bangchang, Kesara; Eursitthichai, Veerachai; Rudi Grams, Hans; Upreti, Senendra R; Ghimire, Prakash; KC, Khagendra; Nisalak, Ananda; Gibbons, Robert V; Fernandez, Stefan

    2013-04-01

    We report on the changing epidemiology of two important flaviviruses in Nepal: Japanese encephalitis (JE) and dengue viruses. Morbidity and mortality in Nepal is in the thousands since JE was introduced in 1978. Nepal launched an extensive laboratory-based JE surveillance in 2004. Nepal experienced a remarkable reduction in disease burden after mass immunizations from 2005 to 2010, when 2,040 JE infections and 205 JE-related deaths were confirmed. With its emergence in 2006, dengue has become a significant challenge in the country, highlighted by a sudden outbreak in 2010 that resulted in 359 confirmed dengue infections. Currently, both viruses cocirculate in Nepal. Here, we document the remarkable expansion of dengue in Nepal, which urgently requires national surveillance to refine the burden and make recommendations regarding control and prevention programs. We believe that the use of existing JE surveillance network for integrated dengue surveillance may represent the most appropriate alternative.

  20. Trypsinized Human Group O Erythrocytes as an Alternative Hemagglutinating Agent for Japanese Encephalitis Virus

    PubMed Central

    Shortridge, K. F.; Hu, L. Y.

    1974-01-01

    Trypsinized human group O erythrocytes were found to be a suitable alternative to gander cells in hemagglutination (HA) and hemagglutination inhibition (HAI) tests for Japanese encephalitis (JE) virus. In the HAI test, no cross-reactions against JE virus were observed with immune sera containing antibody to taxonomically related or unrelated viruses, with mouse brain antigen, or with nonantibody serum inhibitors; specific antibody rise could be detected in an immunized rabbit. Gander and trypsinized human group O cells gave comparable titers in the HAI test, but the latter were preferable since (i) they required less challenging HA antigen, being more sensitive to agglutination by JE virus, and (ii) all human and some animal sera investigated were devoid of natural agglutinins for these cells, thereby eliminating or reducing the need for prior adsorption with packed cells. PMID:4856948

  1. Methods for detecting ATP hydrolysis and nucleic acid unwinding of Japanese encephalitis virus NS3 helicase.

    PubMed

    Fang, Jin'e; Li, Huan; Peng, Guiqing; Cao, Shengbo; Zhen, F Fu; Chen, Huanchun; Song, Yunfeng

    2013-12-01

    Japanese encephalitis virus (JEV) is a mosquito-borne zoonotic pathogen that is prevalent in south-east Asia. Because there is no specific antiviral agent, JEV still causes a high rate of neurologic sequelae and mortality in humans. The helicase encoded by the NS3 gene of JEV has emerged recently as a novel antiviral target for treatment. In this study, a soluble recombinant JEV helicase protein was expressed and purified. Methods for detecting the ATP hydrolysis and nucleic acid unwinding activity were developed by luminescence and fluorescence resonance energy transfer (FRET). The concentrations of enzyme, substrate, capture strand, ATP, and divalent ions were optimised in the ATPase and helicase reactions. The feasibility of using these two methods for high-throughput screening of NS3 helicase inhibitors is discussed.

  2. Japanese viral encephalitis mimicking stroke with an initial manifestation of hemiplegia.

    PubMed

    Chen, Huan-Wen; Ding, Liang-Wen; Lai, Chih-Cheng; Tseng, Tse-Kai; Liu, Wei-Lun

    2012-12-01

    Japanese encephalitis (JE) is an endemic disease in Taiwan. After the program to vaccinate children against JE was implemented in 1968, the incidence of JE gradually started to decrease, but it is still an important infectious disease here. Neurological manifestations in JE vary highly during the initial stage of the disease. Focal neurological symptoms, such as hemiplegia, are rarely reported. A 46-year-old male with the initial presentation of abrupt hemiplegia and fever developed mental confusion after 1 day. No bacterial pathogen was isolated from the blood or cerebrospinal fluid (CSF). A diagnosis of JE was confirmed based on the presence of JE virus-specific immunoglobulin M in the CSF and serum samples. It is necessary to consider JE when a patient presents with abrupt hemiplegia with fever followed with mental confusion and seizure, especially if the patient comes from a JE-endemic area.

  3. Use of Japanese encephalitis vaccine in US travel medicine practices in Global TravEpiNet.

    PubMed

    Deshpande, Bhushan R; Rao, Sowmya R; Jentes, Emily S; Hills, Susan L; Fischer, Marc; Gershman, Mark D; Brunette, Gary W; Ryan, Edward T; LaRocque, Regina C

    2014-10-01

    Few data regarding the use of Japanese encephalitis (JE) vaccine in clinical practice are available. We identified 711 travelers at higher risk and 7,578 travelers at lower risk for JE who were seen at US Global TravEpiNet sites from September of 2009 to August of 2012. Higher-risk travelers were younger than lower-risk travelers (median age = 29 years versus 40 years, P < 0.001). Over 70% of higher-risk travelers neither received JE vaccine during the clinic visit nor had been previously vaccinated. In the majority of these instances, clinicians determined that the JE vaccine was not indicated for the higher-risk traveler, which contradicts current recommendations of the Advisory Committee on Immunization Practices. Better understanding is needed of the clinical decision-making regarding JE vaccine in US travel medicine practices.

  4. 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.

  5. 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

  6. 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.

  7. The appearance of a second genotype of Japanese encephalitis virus in the Australasian region.

    PubMed

    Pyke, A T; Williams, D T; Nisbet, D J; van den Hurk, A F; Taylor, C T; Johansen, C A; Macdonald, J; Hall, R A; Simmons, R J; Mason, R J; Lee, J M; Ritchie, S A; Smith, G A; Mackenzie, J S

    2001-12-01

    In mid-January 2000, the reappearance of Japanese encephalitis (JE) virus activity in the Australasian region was first demonstrated by the isolation of JE virus from 3 sentinel pigs on Badu Island in the Torres Strait. Further evidence of JE virus activity was revealed through the isolation of JE virus from Culex gelidus mosquitoes collected on Badu Island and the detection of specific JE virus neutralizing antibodies in 3 pigs from Saint Pauls community on Moa Island. Nucleotide sequencing and phylogenetic analyses of the premembrane and envelope genes were performed which showed that both the pig and mosquito JE virus isolates (TS00 and TS4152, respectively) clustered in genotype I, along with northern Thai, Cambodian, and Korean isolates. All previous Australasian JE virus isolates belong to genotype II, along with Malaysian and Indonesian isolates. Therefore, for the first time, the appearance and transmission of a second genotype of JE virus in the Australasian region has been demonstrated.

  8. Intensive Circulation of Japanese Encephalitis Virus in Peri-urban Sentinel Pigs near Phnom Penh, Cambodia

    PubMed Central

    Cappelle, Julien; Duong, Veasna; Pring, Long; Kong, Lida; Yakovleff, Maud; Prasetyo, Didot Budi; Peng, Borin; Choeung, Rithy; Duboz, Raphaël; Ong, Sivuth; Sorn, San; Dussart, Philippe; Tarantola, Arnaud; Buchy, Philippe; Chevalier, Véronique

    2016-01-01

    Despite the increased use of vaccination in several Asian countries, Japanese Encephalitis (JE) remains the most important cause of viral encephalitis in Asia in humans with an estimated 68,000 cases annually. Considered a rural disease occurring mainly in paddy-field dominated landscapes where pigs are amplifying hosts, JE may nevertheless circulate in a wider range of environment given the diversity of its potential hosts and vectors. The main objective of this study was to assess the intensity of JE transmission to pigs in a peri-urban environment in the outskirt of Phnom Penh, Cambodia. We estimated the force of JE infection in two cohorts of 15 sentinel pigs by fitting a generalised linear model on seroprevalence monitoring data observed during two four-month periods in 2014. Our results provide evidence for intensive circulation of JE virus in a periurban area near Phnom Penh, the capital and most populated city of Cambodia. Understanding JE virus transmission in different environments is important for planning JE virus control in the long term and is also an interesting model to study the complexity of vector-borne diseases. Collecting quantitative data such as the force of infection will help calibrate epidemiological model that can be used to better understand complex vector-borne disease epidemiological cycles. PMID:27926937

  9. Inhibition of Japanese encephalitis virus (JEV) replication by specific RNA aptamer against JEV methyltransferase.

    PubMed

    Han, Seung Ryul; Lee, Seong-Wook

    2017-01-29

    Japanese encephalitis virus (JEV) is the most common etiological agent of epidemic viral encephalitis. JEV encodes a single methyltransferase (MTase) domain located at the N-terminal region of the viral nonstructural protein NS5. JEV MTase is essential for viral replication and specifically catalyzes methylation of the viral RNA cap, which occurs exclusively in the cytoplasm. Therefore, JEV MTase is a potential target for antiviral therapy. Here, we identified specific and avid RNA aptamer (Kd ∼ 12 nM) with modified 2'-O-methyl pyrimidines against JEV MTase. The RNA aptamer efficiently inhibited viral cap methylation activity of MTase and interfered with JEV production in cells. Moreover, we generated a 24-mer truncated aptamer that could specifically bind to JEV MTase with high affinity (Kd ∼16 nM). The 24-mer aptamer efficiently inhibited JEV production and replication in cells. Therefore, MTase-specific RNA aptamer might be useful as an anti-JEV agent.

  10. An outbreak of Japanese encephalitis after two decades in Odisha, India.

    PubMed

    Dwibedi, Bhagirathi; Mohapatra, Namita; Rathore, Sushil Kumar; Panda, Maheswar; Pati, Satya Sundar; Sabat, Jyotsnamayee; Thakur, Bandana; Panda, Sailendra; Kar, Shantanu Kumar

    2015-12-01

    Sudden deaths in children due to acute encephalitis syndrome (AES) from a tribal dominated district of Malkangiri in Odisha, India, was reported during September-November, 2012. The investigation was carried out to search for the possible viral aetiology that caused this outbreak. Clinico-epidemiological survey and seromolecular investigation were carried out to confirm the viral aetiology. Two hundred seventy two suspected cases with 24 deaths were observed. The patients presented with low to moderate grade fever (87%), headache (43%), vomiting (27%), cold (18%), cough (17%), body ache (15%), joint pain (15%), rash (15%), abdomen pain (9%), lethargy (5%), altered sensorium (8%), convulsion (2%), diarrhoea (3%), and haematemesis (3%). Laboratory investigation showed Japanese encephalitis virus (JEV) IgM in 13.8 per cent (13/94) in blood samples and JEV RNA in one of two cerebrospinal fluid (CSF) samples. Paddy fields close to the houses, high pig to cattle ratio, high density (33 per man hour density) of Culex vishnui mosquitoes, low socio-economic status and low health awareness in the tribal population were observed. This report confirmed the outbreak of JEV infection in Odisha after two decades.

  11. Molecular Epidemiology of Japanese Encephalitis Virus in Mosquitoes during an Outbreak in China, 2013

    PubMed Central

    Tao, Zexin; Liu, Guifang; Wang, Min; Wang, Huanyu; Lin, Xiaojuan; Song, Lizhi; Wang, Suting; Wang, Haiyan; Liu, Xiaodong; Cui, Ning; Song, Yanyan; Xu, Aiqiang

    2014-01-01

    Japanese encephalitis virus (JEV) can cause serious encephalitis and Culex mosquitoes are the primary vector. In 2013, a JE outbreak occurred in Shandong Province, China with 407 confirmed cases, including 11 deaths. An investigation on JEV in mosquitoes during the outbreak was conducted. A total of 14,719 mosquitoes were collected at 3 sites. For the 12,695 Culex tritaeniorhynchus mosquitoes, 88/201 pooled samples were positive by RT-PCR for the presence of the pre-membrane or envelope protein coding genes. The maximum likelihood estimates of JEV positive individuals per 1,000 vectors were 12.0, 7.2, and 6.0 in the 3 sites respectively with an overall estimate of 9.1. Phylogenetic analysis on these pre-membrane (n = 72) and envelope (n = 26) sequences with those of reference strains revealed they belonged to genotype I. This study describes the molecular epidemiology of JEV and suggests the high infection rate in mosquitoes is an important factor for the outbreak. PMID:24809635

  12. Human T cell responses to Japanese encephalitis virus in health and disease.

    PubMed

    Turtle, Lance; Bali, Tanushka; Buxton, Gemma; Chib, Savita; Chan, Sajesh; Soni, Mohammed; Hussain, Mohammed; Isenman, Heather; Fadnis, Prachi; Venkataswamy, Manjunatha M; Satishkumar, Vishali; Lewthwaite, Penny; Kurioka, Ayako; Krishna, Srinivasa; Shankar, M Veera; Ahmed, Riyaz; Begum, Ashia; Ravi, Vasanthapuram; Desai, Anita; Yoksan, Sutee; Fernandez, Stefan; Willberg, Christian B; Kloverpris, Henrik N; Conlon, Christopher; Klenerman, Paul; Satchidanandam, Vijaya; Solomon, Tom

    2016-06-27

    Japanese encephalitis (JE) virus (JEV) is an important cause of encephalitis in children of South and Southeast Asia. However, the majority of individuals exposed to JEV only develop mild symptoms associated with long-lasting adaptive immunity. The related flavivirus dengue virus (DENV) cocirculates in many JEV-endemic areas, and clinical data suggest cross-protection between DENV and JEV. To address the role of T cell responses in protection against JEV, we conducted the first full-breadth analysis of the human memory T cell response using a synthetic peptide library. Ex vivo interferon-γ (IFN-γ) responses to JEV in healthy JEV-exposed donors were mostly CD8(+) and targeted nonstructural (NS) proteins, whereas IFN-γ responses in recovered JE patients were mostly CD4(+) and targeted structural proteins and the secreted protein NS1. Among patients, a high quality, polyfunctional CD4(+) T cell response was associated with complete recovery from JE. T cell responses from healthy donors showed a high degree of cross-reactivity to DENV that was less apparent in recovered JE patients despite equal exposure. These data reveal divergent functional CD4(+) and CD8(+) T cell responses linked to different clinical outcomes of JEV infection, associated with distinct targeting and broad flavivirus cross-reactivity including epitopes from DENV, West Nile, and Zika virus.

  13. Human T cell responses to Japanese encephalitis virus in health and disease

    PubMed Central

    Bali, Tanushka; Buxton, Gemma; Chib, Savita; Chan, Sajesh; Soni, Mohammed; Hussain, Mohammed; Isenman, Heather; Fadnis, Prachi; Venkataswamy, Manjunatha M.; Satishkumar, Vishali; Lewthwaite, Penny; Kurioka, Ayako; Krishna, Srinivasa; Shankar, M. Veera; Ahmed, Riyaz; Begum, Ashia; Ravi, Vasanthapuram; Desai, Anita; Yoksan, Sutee; Fernandez, Stefan; Willberg, Christian B.; Kloverpris, Henrik N.; Conlon, Christopher; Satchidanandam, Vijaya; Solomon, Tom

    2016-01-01

    Japanese encephalitis (JE) virus (JEV) is an important cause of encephalitis in children of South and Southeast Asia. However, the majority of individuals exposed to JEV only develop mild symptoms associated with long-lasting adaptive immunity. The related flavivirus dengue virus (DENV) cocirculates in many JEV-endemic areas, and clinical data suggest cross-protection between DENV and JEV. To address the role of T cell responses in protection against JEV, we conducted the first full-breadth analysis of the human memory T cell response using a synthetic peptide library. Ex vivo interferon-γ (IFN-γ) responses to JEV in healthy JEV-exposed donors were mostly CD8+ and targeted nonstructural (NS) proteins, whereas IFN-γ responses in recovered JE patients were mostly CD4+ and targeted structural proteins and the secreted protein NS1. Among patients, a high quality, polyfunctional CD4+ T cell response was associated with complete recovery from JE. T cell responses from healthy donors showed a high degree of cross-reactivity to DENV that was less apparent in recovered JE patients despite equal exposure. These data reveal divergent functional CD4+ and CD8+ T cell responses linked to different clinical outcomes of JEV infection, associated with distinct targeting and broad flavivirus cross-reactivity including epitopes from DENV, West Nile, and Zika virus. PMID:27242166

  14. Cloning and application of recombinant dengue virus prM-M protein for serodiagnosis of dengue virus infection.

    PubMed

    Wichit, Sineewanlaya; Yongpradoem, Hatairat; Surasombatpattana, Pornapat; Leaungwuttiwong, Pornsawan; Kalambaheti, Thareerat; Jampangern, Wipawee; Jittmittraphap, Akanitt

    2013-03-01

    We studied the use of the precursor to the M structural protein (prM) found only on the surface of mature dengue virus as a target protein to detect dengue virus infection. Recombinant D2-16681 prM-M protein was constructed and tested for immunogenicity with dengue and Japanese encephalitis patient sera by Western blot analysis and indirect ELISA. The sensitivity and specificity of indirect ELISA were 48.1 and 85.5%, respectively, and Western blot assay were 23.1 and 98.7%, respectively, for detection of dengue virus. Although the sensitivity of the indirect ELISA is low, the indirect ELISA using recombinant D2-16681 prM-M proteins as antigen may be used for early detection of dengue virus infection.

  15. 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.

  16. Safety of Japanese encephalitis live attenuated vaccination in post-marketing surveillance in Guangdong, China, 2005-2012.

    PubMed

    Liu, Yu; Lin, Hualiang; Zhu, Qi; Wu, Chenggang; Zhao, Zhanjie; Zheng, Huizhen

    2014-03-26

    We reviewed the adverse events following immunization of live attenuated Japanese encephalitis vaccine in Guangdong Province, China. During the period of 2005-2012, 23 million doses of live attenuated Japanese encephalitis vaccine were used and 1426 adverse events were reported (61.24 per million doses); of which, 570 (40%) were classified as allergic reactions (24.48 per million doses), 31 (2%) were neurologic events (1.33 per million doses), and 36 (2.5%) were diagnosed as serious adverse events (1.55 per million doses). This study suggests that the JEV-L has a reasonable safety profile, most adverse events are relatively mild, with relatively rare neurologic events being observed.

  17. Inference of Japanese encephalitis virus ecological and evolutionary dynamics from passive and active virus surveillance

    PubMed Central

    Pham, Truc T.; Meng, Shengli; Sun, Yan; Lv, Wenli; Bahl, Justin

    2016-01-01

    A comprehensive monitoring strategy is vital for tracking the spread of mosquito-borne Japanese encephalitis virus (JEV), the leading cause of viral encephalitis in Asia. Virus detection consists of passive surveillance of primarily humans and swine, and/or active surveillance in mosquitoes, which may be a valuable proxy in providing insights into ecological processes underlying the spread and persistence of JEV. However, it has not been well characterized whether passive surveillance alone can capture the circulating genetic diversity to make reasonable inferences. Here, we develop phylogenetic models to infer JEV host changes, spatial diffusion patterns, and evolutionary dynamics from data collected through active and passive surveillance. We evaluate the feasibility of using JEV sequence data collected from mosquitoes to estimate the migration histories of genotypes GI and GIII. We show that divergence times estimated from this dataset were comparable to estimates from all available data. Increasing the amount of data collected from active surveillance improved time of most recent common ancestor estimates and reduced uncertainty. Phylogenetic estimates using all available data and only mosquito data from active surveillance produced similar results, showing that GI epidemics were widespread and diffused significantly faster between regions than GIII. In contrast, GIII outbreaks were highly structured and unlinked suggesting localized, unsampled infectious sources. Our results show that active surveillance of mosquitoes can sufficiently capture circulating genetic diversity of JEV to confidently estimate spatial and evolutionary patterns. While surveillance of other hosts could contribute to more detailed disease tracking and evaluation, comprehensive JEV surveillance programs should include systematic surveillance in mosquitoes to infer the most complete patterns for epidemiology, and risk assessment. PMID:27774302

  18. Inference of Japanese encephalitis virus ecological and evolutionary dynamics from passive and active virus surveillance.

    PubMed

    Pham, Truc T; Meng, Shengli; Sun, Yan; Lv, Wenli; Bahl, Justin

    2016-01-01

    A comprehensive monitoring strategy is vital for tracking the spread of mosquito-borne Japanese encephalitis virus (JEV), the leading cause of viral encephalitis in Asia. Virus detection consists of passive surveillance of primarily humans and swine, and/or active surveillance in mosquitoes, which may be a valuable proxy in providing insights into ecological processes underlying the spread and persistence of JEV. However, it has not been well characterized whether passive surveillance alone can capture the circulating genetic diversity to make reasonable inferences. Here, we develop phylogenetic models to infer JEV host changes, spatial diffusion patterns, and evolutionary dynamics from data collected through active and passive surveillance. We evaluate the feasibility of using JEV sequence data collected from mosquitoes to estimate the migration histories of genotypes GI and GIII. We show that divergence times estimated from this dataset were comparable to estimates from all available data. Increasing the amount of data collected from active surveillance improved time of most recent common ancestor estimates and reduced uncertainty. Phylogenetic estimates using all available data and only mosquito data from active surveillance produced similar results, showing that GI epidemics were widespread and diffused significantly faster between regions than GIII. In contrast, GIII outbreaks were highly structured and unlinked suggesting localized, unsampled infectious sources. Our results show that active surveillance of mosquitoes can sufficiently capture circulating genetic diversity of JEV to confidently estimate spatial and evolutionary patterns. While surveillance of other hosts could contribute to more detailed disease tracking and evaluation, comprehensive JEV surveillance programs should include systematic surveillance in mosquitoes to infer the most complete patterns for epidemiology, and risk assessment.

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

    PubMed Central

    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. PMID:27703358

  20. The Potential Use of Wolbachia-Based Mosquito Biocontrol Strategies for Japanese Encephalitis

    PubMed Central

    Jeffries, Claire L.; Walker, Thomas

    2015-01-01

    Japanese encephalitis virus (JEV) is a zoonotic pathogen transmitted by the infectious bite of Culex mosquitoes. The virus causes the development of the disease Japanese encephalitis (JE) in a small proportion of those infected, predominantly affecting children in eastern and southern Asia. Annual JE incidence estimates range from 50,000–175,000, with 25%–30% of cases resulting in mortality. It is estimated that 3 billion people live in countries in which JEV is endemic. The virus exists in an enzootic transmission cycle, with mosquitoes transmitting JEV between birds as reservoir hosts and pigs as amplifying hosts. Zoonotic infection occurs as a result of spillover events from the main transmission cycle. The reservoir avian hosts include cattle egrets, pond herons, and other species of water birds belonging to the family Ardeidae. Irrigated rice fields provide an ideal breeding ground for mosquitoes and attract migratory birds, maintaining the transmission of JEV. Although multiple vaccines have been developed for JEV, they are expensive and require multiple doses to maintain efficacy and immunity. As humans are a “dead-end” host for the virus, vaccination of the human population is unlikely to result in eradication. Therefore, vector control of the principal mosquito vector, Culex tritaeniorhynchus, represents a more promising strategy for reducing transmission. Current vector control strategies include intermittent irrigation of rice fields and space spraying of insecticides during outbreaks. However, Cx. Tritaeniorhynchus is subject to heavy exposure to pesticides in rice fields, and as a result, insecticide resistance has developed. In recent years, significant advancements have been made in the potential use of the bacterial endosymbiont Wolbachia for mosquito biocontrol. The successful transinfection of Wolbachia strains from Drosophila flies to Aedes (Stegomyia) mosquitoes has resulted in the generation of “dengue-refractory” mosquito lines

  1. Serosurveillance for Japanese encephalitis virus in wild birds captured in Korea.

    PubMed

    Yang, Dong-Kun; Oh, Yoon-I; Kim, Hye-Ryoung; Lee, Youn-Jeong; Moon, Oun-Kyong; Yoon, Hachung; Kim, Byounghan; Lee, Kyung-Woo; Song, Jae-Young

    2011-12-01

    Climate change induced by recent global warming may have a significant impact on vector-borne and zoonotic diseases. For example, the distribution of Japanese encephalitis virus (JEV) has expanded into new regions. We surveyed the levels of hemagglutination-inhibition (HI) antibodies against JEV (Family Flaviviridae, genus Flavivirus) in wild birds captured in Korea. Blood samples were collected from 1,316 wild birds including the following migratory birds: Oceanodroma castro (n = 4), Anas formosa (n = 7), Anas penelope (n = 20), Fulica atra (n = 30), Anas acuta (n = 89), Anas crecca (n = 154), Anas platyrhynchos (n = 214), Aix galericulata (n = 310), and Anas poecilorhyncha (n = 488). All were captured in 16 locations in several Korea provinces between April 2007 and December 2009. Out of the 1,316 serum samples tested, 1,141 (86.7%) were positive for JEV. Wild birds captured in 2009 had a higher seroprevalence of ant-JEV antibodies than those captured in 2007. Wild birds with an HI antibody titer of 1 : 1,280 or higher accounted for 21.2% (280/1,316) of the animals tested. These findings indicated that wild birds from the region examined in our study have been exposed to JEV and may pose a high risk for introducing a new JEV genotype into Korea.

  2. Sphingomyelin generated by sphingomyelin synthase 1 is involved in attachment and infection with Japanese encephalitis virus

    PubMed Central

    Taniguchi, Makoto; Tasaki, Takafumi; Ninomiya, Hideaki; Ueda, Yoshibumi; Kuremoto, Koh-ichi; Mitsutake, Susumu; Igarashi, Yasuyuki; Okazaki, Toshiro; Takegami, Tsutomu

    2016-01-01

    Japanese encephalitis virus (JEV) is a mosquito-borne RNA virus which infects target cells via the envelope protein JEV-E. However, its cellular targets are largely unknown. To investigate the role of sphingomyelin (SM) in JEV infection, we utilized SM-deficient immortalized mouse embryonic fibroblasts (tMEF) established from SM synthase 1 (SMS1)/SMS2 double knockout mice. SMS deficiency significantly reduced both intracellular and extracellular JEV levels at 48 h after infection. Furthermore, after 15 min treatment with JEV, the early steps of JEV infection such as attachment and cell entry were also diminished in SMS-deficient tMEFs. The inhibition of JEV attachment and infection were recovered by overexpression of SMS1 but not SMS2, suggesting SMS1 contributes to SM production for JEV attachment and infection. Finally, intraperitoneal injection of JEV into SMS1-deficient mice showed an obvious decrease of JEV infection and its associated pathologies, such as meningitis, lymphocyte infiltration, and elevation of interleukin 6, compared with wild type mice. These results suggest that SMS1-generated SM on the plasma membrane is related in JEV attachment and subsequent infection, and may be a target for inhibition of JEV infection. PMID:27892528

  3. Cross-protection induced by Japanese encephalitis vaccines against different genotypes of Dengue viruses in mice.

    PubMed

    Li, Jieqiong; Gao, Na; Fan, Dongying; Chen, Hui; Sheng, Ziyang; Fu, Shihong; Liang, Guodong; An, Jing

    2016-01-28

    Dengue viruses (DENVs) and Japanese encephalitis virus (JEV) are closely related mosquito-borne flaviviruses that cause very high global disease burdens. Although cross-reactivity and cross-protection within flaviviruses have been demonstrated, the effect of JEV vaccination on susceptibility to DENV infection has not been well elucidated. In this study, we found that vaccination with the JEV inactivated vaccine (INV) and live attenuated vaccine (LAV) could induce cross-immune responses and cross-protection against DENV1-4 in mice. Despite the theoretical risk of immune enhancement, no increased mortality was observed in our mouse model. Additionally, low but consistently detectable cross-neutralizing antibodies against DENV2 and DENV3 were also observed in the sera of JEV vaccine-immunized human donors. The results suggested that both JEV-LAV and JEV-INV could elicit strong cross-immunity and protection against DENVs, indicating that inoculation with JEV vaccines may influence the distribution of DENVs in co-circulated areas and that the cross-protection induced by JEV vaccines against DENVs might provide important information in terms of DENV prevention.

  4. Cell type-dependent RNA recombination frequency in the Japanese encephalitis virus.

    PubMed

    Chiang, Wei-Wei; Chuang, Ching-Kai; Chao, Mei; Chen, Wei-June

    2014-01-01

    Japanese encephalitis virus (JEV) is one of approximately 70 flaviviruses, frequently causing symptoms involving the central nervous system. Mutations of its genomic RNA frequently occur during viral replication, which is believed to be a force contributing to viral evolution. Nevertheless, accumulating evidences show that some JEV strains may have actually arisen from RNA recombination between genetically different populations of the virus. We have demonstrated that RNA recombination in JEV occurs unequally in different cell types. In the present study, viral RNA fragments transfected into as well as viral RNAs synthesized in mosquito cells were shown not to be stable, especially in the early phase of infection possibly via cleavage by exoribonuclease. Such cleaved small RNA fragments may be further degraded through an RNA interference pathway triggered by viral double-stranded RNA during replication in mosquito cells, resulting in a lower frequency of RNA recombination in mosquito cells compared to that which occurs in mammalian cells. In fact, adjustment of viral RNA to an appropriately lower level in mosquito cells prevents overgrowth of the virus and is beneficial for cells to survive the infection. Our findings may also account for the slower evolution of arboviruses as reported previously.

  5. How environmental conditions impact mosquito ecology and Japanese encephalitis: an eco-epidemiological approach.

    PubMed

    Tian, Huai-Yu; Bi, Peng; Cazelles, Bernard; Zhou, Sen; Huang, Shan-Qian; Yang, Jing; Pei, Yao; Wu, Xiao-Xu; Fu, Shi-Hong; Tong, Shi-Lu; Wang, Huan-Yu; Xu, Bing

    2015-06-01

    Japanese encephalitis (JE) is one of the major vector-borne diseases in Southeast Asia and the Western Pacific region, posing a threat to human health. In rural and suburban areas, traditional rice farming and intensive pig breeding provide an ideal environment for both mosquito development and the transmission of JEV among human beings. Combining surveillance data for mosquito vectors, human JE cases, and environmental conditions in Changsha, China, 2004-2009, generalized threshold models were constructed to project the mosquito and JE dynamics. Temperature and rainfall were found to be closely associated with mosquito density at 1, and 4month lag, respectively. The two thresholds, maximum temperature of 22-23°C for mosquito development and minimum temperature of 25-26°C for JEV transmission, play key roles in the ecology of JEV. The model predicts that, in the upper regime, a 1g/m(3) increase in absolute humidity would on average increase human cases by 68-84%. A shift in mosquito species composition in 2007 was observed, and possibly caused by a drought. Effective predictive models could be used in risk management to provide early warnings for potential JE transmission.

  6. 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.

  7. 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.

  8. Seroconversion to Japanese Encephalitis Virus Among U.S. Infantry Forces in Korea.

    PubMed

    Eick-Cost, Angelia A; Hu, Zheng; Klein, Terry A; Putnak, Robert J; Jarman, Richard G

    2015-11-01

    Japanese encephalitis virus (JEV) is endemic in the Republic of Korea (ROK), posing a medical threat to more than 29,000 U.S. Forces military personnel currently deployed in the ROK. The objective of this study was to provide data on the risk of JEV exposure among U.S. Forces in the ROK. One thousand U.S. Army Soldiers were randomly selected for the study from the cohort of infantry Soldiers deployed in the ROK for a period of at least 330 days from 2008 to 2011. Pre- and post-deployment serum specimens were tested for the presence of JEV antibodies by plaque reduction neutralization test. A total of 2/1,000 (0.2%) U.S. Army Soldiers post-deployment specimens tested positive for JEV antibody. Results from the pre-deployment specimens indicated one true seroconversion and one with titers suggestive of a JEV infection. These results indicate a low, but nonzero risk of JEV exposure among U.S. Army Soldiers in the ROK.

  9. 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

  10. Neurological sequelae of hospitalized Japanese encephalitis cases in Gansu province, China.

    PubMed

    Yin, Zundong; Wang, Xuxia; Li, Li; Li, Hui; Zhang, Xiaoshu; Li, Junhong; Ning, Guijun; Li, Fengqin; Liang, Xuefeng; Gao, Li; Liang, Xiaofeng; Li, Yixing

    2015-06-01

    We conducted a follow-up survey for 55 Japanese encephalitis (JE) cases 1-2 years after hospital discharge in Gansu province, China. Community-, education-, and gender-matched healthy individuals without history of neurologic disease were selected as the comparison group. All subjects received neurological examination, intelligence quotient (IQ) measurement, adaptive behavior measurement, and Wechsler memory scale (WMS) assessment. We found 43.6% JE cases had at least one nervous system sequelae compared with 3.6% healthy individuals. Among JE cases, 22.4% had subnormal IQ, 18.4% subnormal verbal IQ (VIQ), 20.4% subnormal performance IQ (PIQ), and 78.4% had subnormal memory quotient (MQ). Among healthy individuals, 2.0% had subnormal IQ, VIQ, or PIQ and 8.1% had subnormal MQ. Among adult JE cases, 47.8% and 39.1% had adaptive behavior impairments and intellectual disability, respectively, compared with 18.8% and 9.7% among young cases, respectively. The results showed both adult and young surviving JE cases had significant neurological sequelae and mental disability 1-2 years after discharged.

  11. Detection of antibodies against Japanese encephalitis virus in raccoons, raccoon dogs and wild boars in Japan.

    PubMed

    Ohno, Yoshito; Sato, Hiroshi; Suzuki, Kazuo; Yokoyama, Mayumi; Uni, Shigehiko; Shibasaki, Takahiro; Sashika, Mariko; Inokuma, Hisashi; Kai, Kazushige; Maeda, Ken

    2009-08-01

    Japanese encephalitis virus (JEV) infects numerous animal species including humans, horses and pigs. In this study, antibodies against JEV in feral raccoons (Procyon lotor), wild boars (Sus scrofa) and raccoon dogs (Nyctereutes procyonoides) in Japan were examined. The results showed that 40.7% (22 out of 54), 64.5% (40 out of 62), 69.1% (47 out of 68) and 0% (0 out of 20) of raccoons in Hyogo, Osaka, Wakayama and Hokkaido, respectively, had virus-neutralizing antibodies against JEV. In addition, 83.3% (30 out of 36) of wild boars and 63.2% (12 out of 19) of raccoon dogs in Wakayama were seropositive for JEV. There were no significant differences in seroprevalence of JEV between males and females or between adults and juveniles in these wild animals. JEV seroprevalence was compared between 37 raccoons and 30 wild boars captured in a limited period (November 2007 to February 2008), and we found that wild boars (86.7%) were significantly more seropositive for JEV antibody than raccoons (59.5%). In conclusion, JEV was prevalent in wild mammals, indicating that the possibility of JEV infection in humans may still be high in Japan. In addition, these wild animals may be good sentinels to estimate JEV infection risk in residents, as they live near humans and are not vaccinated.

  12. Cross-protection induced by Japanese encephalitis vaccines against different genotypes of Dengue viruses in mice

    PubMed Central

    Li, Jieqiong; Gao, Na; Fan, Dongying; Chen, Hui; Sheng, Ziyang; Fu, Shihong; Liang, Guodong; An, Jing

    2016-01-01

    Dengue viruses (DENVs) and Japanese encephalitis virus (JEV) are closely related mosquito-borne flaviviruses that cause very high global disease burdens. Although cross-reactivity and cross-protection within flaviviruses have been demonstrated, the effect of JEV vaccination on susceptibility to DENV infection has not been well elucidated. In this study, we found that vaccination with the JEV inactivated vaccine (INV) and live attenuated vaccine (LAV) could induce cross-immune responses and cross-protection against DENV1-4 in mice. Despite the theoretical risk of immune enhancement, no increased mortality was observed in our mouse model. Additionally, low but consistently detectable cross-neutralizing antibodies against DENV2 and DENV3 were also observed in the sera of JEV vaccine-immunized human donors. The results suggested that both JEV-LAV and JEV-INV could elicit strong cross-immunity and protection against DENVs, indicating that inoculation with JEV vaccines may influence the distribution of DENVs in co-circulated areas and that the cross-protection induced by JEV vaccines against DENVs might provide important information in terms of DENV prevention. PMID:26818736

  13. The prM-independent packaging of pseudotyped Japanese encephalitis virus.

    PubMed

    Lee, Hee Jung; Min, Kyung-Il; Lee, Jungeun; Kang, Sin-Hyung; Jeon, Wonkyung; Nam, Jae Hwan; Ju, Young Ran; Kim, Young Bong

    2009-07-30

    As noted in other flaviviruses, the envelope (E) protein of Japanese encephalitis virus (JEV) interacts with a cellular receptor and mediates membrane fusion to allow viral entry into target cells, thus eliciting neutralizing antibody response. The formation of the flavivirus prM/E complex is followed by the cleavage of precursor membrane (prM) and membrane (M) protein by a cellular signalase. To test the effect of prM in JEV biology, we constructed JEV-MuLV pseudotyped viruses that express the prM/E protein or E only. The infectivity and titers of JEV pseudotyped viruses were examined in several cell lines. We also analyzed the neutralizing capacities with anti-JEV sera from JEV-immunized mice. Even though prM is crucial for multiple stages of JEV biology, the JEV-pseudotyped viruses produced with prM/E or with E only showed similar infectivity and titers in several cell lines and similar neutralizing sensitivity. These results showed that JEV-MuLV pseudotyped viruses did not require prM for production of infectious pseudotyped viruses.

  14. Mx Is Not Responsible for the Antiviral Activity of Interferon-α against Japanese Encephalitis Virus

    PubMed Central

    Zhou, Jing; Wang, Shi-Qi; Wei, Jian-Chao; Zhang, Xiao-Min; Gao, Zhi-Can; Liu, Ke; Ma, Zhi-Yong; Chen, Pu-Yan; Zhou, Bin

    2017-01-01

    Mx proteins are interferon (IFN)-induced dynamin-like GTPases that are present in all vertebrates and inhibit the replication of myriad viruses. However, the role Mx proteins play in IFN-mediated suppression of Japanese encephalitis virus (JEV) infection is unknown. In this study, we set out to investigate the effects of Mx1 and Mx2 expression on the interferon-α (IFNα) restriction of JEV replication. To evaluate whether the inhibitory activity of IFNα on JEV is dependent on Mx1 or Mx2, we knocked down Mx1 or Mx2 with siRNA in IFNα-treated PK-15 cells and BHK-21 cells, then challenged them with JEV; the production of progeny virus was assessed by plaque assay, RT-qPCR, and Western blotting. Our results demonstrated that depletion of Mx1 or Mx2 did not affect JEV restriction imposed by IFNα, although these two proteins were knocked down 66% and 79%, respectively. Accordingly, expression of exogenous Mx1 or Mx2 did not change the inhibitory activity of IFNα to JEV. In addition, even though virus-induced membranes were damaged by Brefeldin A (BFA), overexpressing porcine Mx1 or Mx2 did not inhibit JEV proliferation. We found that BFA inhibited JEV replication, not maturation, suggesting that BFA could be developed into a novel antiviral reagent. Collectively, our findings demonstrate that IFNα inhibits JEV infection by Mx-independent pathways. PMID:28075421

  15. 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.

  16. Dengue NS1 and prM antibodies increase the sensitivity of acute dengue diagnosis test and differentiate from Japanese encephalitis infection.

    PubMed

    Gowri Sankar, S; Balaji, T; Venkatasubramani, K; Thenmozhi, V; Dhananjeyan, K J; Paramasivan, R; Tyagi, B K; John Vennison, S

    2014-05-01

    Accurate and early diagnosis of dengue infection is essential for dengue case management. In outbreak conditions, it is essential to include two different tests to diagnose dengue and the choice depends on the number of days after the onset of illness in which the sample is collected. During the laboratory diagnosis of dengue in late acute and convalescent phase by MAC-ELISA, it is necessary to rule out possible cross reactions of closely related flavivirus, such as Japanese encephalitis virus which is commonly co-circulating. In the present investigation, the usefulness of dengue virus NS1 and prM antibodies in diagnosing and differentiating dengue from Japanese encephalitis infection was assessed using samples collected during out-breaks. It was shown here that, detection of antibodies against dengue NS1 and prM proteins increases the sensitivity of dengue diagnosis until 15days. Moreover, detection of antibodies against both proteins was able to differentiate dengue from Japanese encephalitis infection.

  17. Experimental evidence that RNA recombination occurs in the Japanese encephalitis virus

    SciTech Connect

    Chuang, C.-K.; Chen, W.-J.

    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 on 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.

  18. Epidemiological Features of Japanese Encephalitis in Taiwan from 2000 to 2014.

    PubMed

    Chang, Yu-Kang; Chang, Hsiao-Ling; Wu, Ho-Sheng; Chen, Kow-Tong

    2017-02-08

    The incidence of Japanese encephalitis (JE) decreased sharply after the national vaccination program was implemented in Taiwan in 1968. However, cases of JE still occur. The purpose of this study was to assess the epidemiology and vaccination policy for JE in Taiwan. We analyzed the data on JE cases reported to the Taiwan Centers for Disease Control (Taiwan CDC) between 2000 and 2014. During the 15-year study period, a total of 4,474 cases were reported to the Taiwan CDC. Of these, 379 (8.5%) were classified as confirmed cases, and 4,095 (91.5%) were classified as suspected cases. The incidence of JE ranged from 0.59 to 1.61 per 1,000,000 people and peaked in 2007. Men had a higher incidence of JE than women (1.37 versus 0.84 per 1,000,000; P = 0.03). Patients who were 40-59 years of age had a higher incidence than did patients younger than 20 years (1.82 versus 0.23; P < 0.001). Patients who lived in the eastern region of Taiwan had the highest incidence rate of JE (P < 0.001). Compared with those who were not vaccinated with the JE vaccine, patients who received four doses of JE vaccine had a lower risk of suffering from death and/or hospitalization (adjusted odds ratio: 0.26; 95% confidence interval: 0.08-0.90; P = 0.04). JE is still a public health problem in Taiwan, and monitoring JE via diagnostic testing to determine the best vaccination program along with enforcing JE vaccine boosters for adults is necessary to eliminate JE in Taiwan.

  19. Cost-effectiveness of routine immunization to control Japanese encephalitis in Shanghai, China.

    PubMed Central

    Ding, Ding; Kilgore, Paul E.; Clemens, John D.; Wei, Liu; Zhi-Yi, Xu

    2003-01-01

    OBJECTIVE: To assess the cost-effectiveness of inactivated and live attenuated Japanese encephalitis (JE) vaccines given to infants and children in Shanghai. METHODS: A decision-analytical model was constructed in order to compare costs and outcomes for three hypothetical cohorts of 100,000 children followed from birth in 1997 to the age of 30 years who received either no JE vaccine, inactivated JE vaccine (P3), or live attenuated JE vaccine (SA 14-14-2). Cumulative incidences of JE from birth to 30 years of age in the pre-immunization era, i.e. before 1968, were used to estimate expected rates of JE in the absence of vaccination. The economic consequences were measured as cost per case, per death, and per disability-adjusted life year (DALY) averted for the two JE immunization programmes. FINDINGS: In comparison with no JE immunization, a programme using the P3 vaccine would prevent 420 JE cases and 105 JE deaths and would save 6456 DALYs per 100,000 persons; the use of the SA 14-14-2 vaccine would prevent 427 cases and 107 deaths and would save 6556 DALYs per 100,000 persons. Both kinds of immunization were cost saving but the SA 14-14-2 vaccine strategy resulted in a saving that was 47% greater (512,456 US dollars) than that obtained with the P3 vaccine strategy (348,246 US dollars). CONCLUSION: Both JE immunization strategies resulted in cost savings in comparison with no JE immunization. This provides a strong economic rationale for vaccinating against JE in Shanghai and suggests that vaccination against JE might be economically justifiable in other parts of China and in certain other developing countries of Asia where the disease is endemic. PMID:12856051

  20. Genetic diversity of Japanese encephalitis virus isolates obtained from the Indonesian archipelago between 1974 and 1987.

    PubMed

    Schuh, Amy J; Guzman, Hilda; Tesh, Robert B; Barrett, Alan D T

    2013-07-01

    Five genotypes (GI-V) of Japanese encephalitis virus (JEV) have been identified, all of which have distinct geographical distributions and epidemiologies. It is thought that JEV originated in the Indonesia-Malaysia region from an ancestral virus. From that ancestral virus GV diverged, followed by GIV, GIII, GII, and GI. Genotype IV appears to be confined to the Indonesia-Malaysia region, as GIV has been isolated in Indonesia from mosquitoes only, while GV has been isolated on three occasions only from a human in Malaysia and mosquitoes in China and South Korea. In contrast, GI-III viruses have been isolated throughout Asia and Australasia from a variety of hosts. Prior to this study only 13 JEV isolates collected from the Indonesian archipelago had been studied genetically. Therefore the sequences of the envelope (E) gene of 24 additional Indonesian JEV isolates, collected throughout the archipelago between 1974 and 1987, were determined and a series of molecular adaptation analyses were performed. Phylogenetic analysis indicated that over a 14-year time span three genotypes of JEV circulated throughout Indonesia, and a statistically significant association between the year of virus collection and genotype was revealed: isolates collected between 1974 and 1980 belonged to GII, isolates collected between 1980 and 1981 belonged to GIV, and isolates collected in 1987 belonged to GIII. Interestingly, three of the GII Indonesian isolates grouped with an isolate that was collected during the JE outbreak that occurred in Australia in 1995, two of the GIII Indonesian isolates were closely related to a Japanese isolate collected 40 years previously, and two Javanese GIV isolates possessed six amino acid substitutions within the E protein when compared to a previously sequenced GIV isolate collected in Flores. Several amino acids within the E protein of the Indonesian isolates were found to be under directional evolution and/or co-evolution. Conceivably, the tropical climate

  1. Genetic Diversity of Japanese Encephalitis Virus Isolates Obtained from the Indonesian Archipelago Between 1974 and 1987

    PubMed Central

    Schuh, Amy J.; Guzman, Hilda; Tesh, Robert B.

    2013-01-01

    Abstract Five genotypes (GI–V) of Japanese encephalitis virus (JEV) have been identified, all of which have distinct geographical distributions and epidemiologies. It is thought that JEV originated in the Indonesia-Malaysia region from an ancestral virus. From that ancestral virus GV diverged, followed by GIV, GIII, GII, and GI. Genotype IV appears to be confined to the Indonesia-Malaysia region, as GIV has been isolated in Indonesia from mosquitoes only, while GV has been isolated on three occasions only from a human in Malaysia and mosquitoes in China and South Korea. In contrast, GI–III viruses have been isolated throughout Asia and Australasia from a variety of hosts. Prior to this study only 13 JEV isolates collected from the Indonesian archipelago had been studied genetically. Therefore the sequences of the envelope (E) gene of 24 additional Indonesian JEV isolates, collected throughout the archipelago between 1974 and 1987, were determined and a series of molecular adaptation analyses were performed. Phylogenetic analysis indicated that over a 14-year time span three genotypes of JEV circulated throughout Indonesia, and a statistically significant association between the year of virus collection and genotype was revealed: isolates collected between 1974 and 1980 belonged to GII, isolates collected between 1980 and 1981 belonged to GIV, and isolates collected in 1987 belonged to GIII. Interestingly, three of the GII Indonesian isolates grouped with an isolate that was collected during the JE outbreak that occurred in Australia in 1995, two of the GIII Indonesian isolates were closely related to a Japanese isolate collected 40 years previously, and two Javanese GIV isolates possessed six amino acid substitutions within the E protein when compared to a previously sequenced GIV isolate collected in Flores. Several amino acids within the E protein of the Indonesian isolates were found to be under directional evolution and/or co-evolution. Conceivably, the

  2. THE COMPLEMENT FIXATION TEST IN THE DIAGNOSIS OF VIRUS INFECTIONS OF THE CENTRAL NERVOUS SYSTEM.

    PubMed

    Casals, J; Palacios, R

    1941-10-31

    A specific complement fixation test can be obtained in various central nervous system virus infections by using as antigens emulsions of infected brain tissue, freezing and thawing the brain emulsion, and then centrifuging it in an angle head centrifuge at 3500 R.P.M. for 1 hour. The method has proved reliable in the case of rabies, St. Louis encephalitis, Japanese B encephalitis, lymphocytic choriomeningitis, Eastern equine encephalomyelitis, Western equine encephalomyelitis, louping ill, and spontaneous encephalomyelitis of mice (Theiler's disease). The specificity of the reaction, regardless of the virus involved, requires different temperatures of inactivation of the sera according to animal species: 56 degrees C. for guinea pig, 60 degrees C. for mouse, and 65 degrees C. for rabbit and dog sera, all heated for 20 minutes. For human sera a temperature of inactivation of 60 degrees C. also for 20 minutes has been adopted; at this temperature the reaction is in general specific. Complement-fixing antibodies in high titre were found in the sera of rabbits, guinea pigs, mice, and dogs immunized with rabies virus. Complement-fixing antibodies were present in high titre in sera drawn from two persons 8 years after an attack of louping ill, from five persons 2(1/2) years after an attack of Eastern equine encephalomyelitis, and from two persons 2(1/2) years after Western equine encephalomyelitis. In cases of St. Louis encephalitis and lymphocytic choriomeningitis, complement-fixing antibodies have been found shortly following infection but not after long periods.

  3. Generation and characterization of a new mammalian cell line continuously expressing virus-like particles of Japanese encephalitis virus for a subunit vaccine candidate

    PubMed Central

    2014-01-01

    Background Japanese encephalitis virus (JEV) is the most important cause of epidemic encephalitis in most Asian regions. There is no specific treatment available for Japanese encephalitis, and vaccination is the only effective way to prevent JEV infection in humans and domestic animals. The purpose of this study is to establish a new mammalian cell line stably and efficiently expressing virus-like particle of JEV for potential use of JEV subunit vaccine. Results We generated a new cell clone (BJ-ME cells) that stably produces a secreted form of Japanese encephalitis virus (JEV) virus-like particle (VLP). The BJ-ME cells were engineered by transfecting BHK-21 cells with a code-optimized cDNA encoding JEV prM and E protein expression plasmid. Cell line BJ-ME can stably produces a secreted form of Japanese encephalitis virus virus-like particle (JEV-VLP) which contains the JEV envelope glycoprotein (E) and membrane protein (M). The amount of JEV-VLP antigen released into the culture fluid of BJ-ME cells was as high as 15–20 μg/ml. JEV-VLP production was stable after multiple cell passages and 100% cell expression was maintained without detectable cell fusion or apoptosis. Cell culture fluid containing the JEV-VLP antigen could be harvested five to seven times continuously at intervals of 4–6 days while maintaining the culture. Mice immunized with the JEV-VLP antigen with or without adjuvant developed high titers of neutralizing antibodies and 100% protection against lethal JEV challenge. Conclusion These results suggest that the recombinant JEV-VLP antigen produced by the BJ-ME cell line is an effective, safe and affordable subunit Japanese encephalitis vaccine candidate, especially for domestic animals such as pig and horse. PMID:25011456

  4. [ZIKA--VIRUS INFECTION].

    PubMed

    Velev, V

    2016-01-01

    This review summarizes the knowledge of the scientific community for Zika-virus infection. It became popular because of severe congenital damage causes of CNS in newborns whose mothers are infected during pregnancy, as well as the risk of pandemic distribution. Discusses the peculiarities of the biology and ecology of vectors--blood-sucking mosquitoes Aedes; stages in the spread of infection and practical problems which caused during pregnancy. Attention is paid to the recommendations that allow leading national and international medical organizations to deal with the threat Zika-virus infection.

  5. 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.

  6. Japanese Encephalitis in Assam, India: Need to Increase Healthcare Workers’ Understanding to Improve Health Care

    PubMed Central

    Ahmad, Akram; Khan, Muhammad Umair; Gogoi, Lakhya Jyoti; Kalita, Manabendra; Sikdar, Atul Prasad; Pandey, Sureshwar; Dhingra, Sameer

    2015-01-01

    Introduction Japanese encephalitis (JE) is a major cause of high morbidity and mortality in several states across India. However, in 2014, a sharp rise was observed in the number of cases of JE in north-eastern Assam state, and 51% of the total cases of JE in India were reported from the Assam in the same year. In this regard, a study was conducted to evaluate the knowledge and attitudes of healthcare workers in Darrang, a district of Assam highly affected by JE. Methods A cross sectional study was conducted for 2 months among HCWs in the major district hospital of Darrang, Assam. A pre-tested, self-administered questionnaire was used to collect data from the participants. Convenience sampling approach was used to collect data from different departments of the hospitals. Descriptive and logistic regression analyses were used to express the results. Results The knowledge of HCWs regarding JE was poor with a mean knowledge score of 11.02±2.39 (out of 17), while their attitudes were positive with a mean attitudes score of 43.16± 2.47 (ranging from 13 to 52). Overall, 40.4% and 74.3% of participants demonstrated good knowledge and positive attitudes respectively. Cut-off score for good knowledge and positive attitudes toward JE was set as ≥12 and >40 respectively. Older participants (40–49 years) and experienced workers (>10 years) were significantly associated with good knowledge as compared to their referent group (p<0.05), while knowledge of nurses and other orderlies were significantly lower than physicians (p<0.01). Similar factors were associated with the positive attitudes of the participants with the exception of experience. Television was the major source of information regarding JE reported by HCWs (79%). Conclusion Although the knowledge was not optimized, HCWs exhibited positive attitudes towards JE. Future research is required to design, implement and evaluate interventions to improve the knowledge of JE among HCWs. PMID:26296212

  7. 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

  8. Laboratory Transmission of Japanese Encephalitis, West Nile Viruses and Getah by Mosquitoes (Diptera:Culicidae) Collected Near Camp Greaves, Gyeonggi Province, Republic of Korea, 2003

    DTIC Science & Technology

    2006-02-28

    WNV)arebothmembers of the JEV serogroup (fam- ily Flaviviridae , genus Flavivirus). Although most in- fections in humans with either of these viruses...ability to transmitWestNile virus (familyFlaviviridae, genus Flavivirus, WNV), Japanese encephalitis virus (family Flaviviridae , genus Flavivirus, JEV...and Getah virus (family Togaviridae , genus Alphavirus, GETV) under laboratory conditions. Both Culex pipiens pallens Coquillett and Culex

  9. 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.

  10. 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.

  11. 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.

  12. Mosquito records from a hot and dry climatic area experiencing frequent outbreaks of Japanese encephalitis, Bellary district, Karnataka, India.

    PubMed

    Kanojia, P C; Jamgaonkar, A V

    2008-03-01

    Mosquito species occurring in Bellary district, Karnataka, India were surveyed for Japanese encephalitis (JE) and West Nile virus (WNV) from 2001 to 2003. A total of 37 mosquito species in 6 genera were recovered from larval and adult habitats. Aedes, Anopheles and Culex were represented by 11 species each, Mansonia by 2 species, and Armigeres and Lutzia by a single species. A total of 68,506 mosquitoes belonging to 20 species were collected at dusk. Most (74.6%) were Cx. tritaeniorhynchus and occurred in 2 peaks of abundance in February (304 per man hour density [PMHD]) and October (465 PMHD). The mosquito fauna of Bellary district is not diverse, possibly because of the hot and dry climatic conditions in the area.

  13. Emergence of Usutu virus, an African mosquito-borne flavivirus of the Japanese encephalitis virus group, central Europe.

    PubMed

    Weissenböck, Herbert; Kolodziejek, Jolanta; Url, Angelika; Lussy, Helga; Rebel-Bauder, Barbara; Nowotny, Norbert

    2002-07-01

    During late summer 2001 in Austria, a series of deaths in several species of birds occurred, similar to the beginning of the West Nile virus (WNV) epidemic in the United States. We necropsied the dead birds and examined them by various methods; pathologic and immunohistologic investigations suggested a WNV infection. Subsequently, the virus was isolated, identified, partially sequenced, and subjected to phylogenetic analysis. The isolates exhibited 97% identity to Usutu virus (USUV), a mosquito-borne Flavivirus of the Japanese encephalitis virus group; USUV has never previously been observed outside Africa nor associated with fatal disease in animals or humans. If established in central Europe, this virus may have considerable effects on avian populations; whether USUV has the potential to cause severe human disease is unknown.

  14. Flower-like ZnO nanostructure assisted loop-mediated isothermal amplification assay for detection of Japanese encephalitis virus.

    PubMed

    Ma, Yonghua; Lu, Yan; Guan, Guiquan; Luo, Jianxun; Niu, Qingli; Liu, Junlong; Yin, Hong; Liu, Guangyuan

    2017-03-15

    In this study, we described a novel and effective flower-like ZnO nanostructure assisted Reverse Transcription Loop-Mediated Isothermal Amplification (RT-LAMP) method to detect Japanese Encephalitis Virus (JEV). The effects of different concentrations of ZnO nanoflower on the RT-LAMP reaction were investigated. With the increase of concentration of ZnO nanoflower, RT-LAMP reaction obtained optimization, until the concentration exceeded 1.5nM, RT-LAMP reaction was inhibited. Made 1nM as optimum concentration of ZnO nanoflower, we found that optimum RT-LAMP reaction temperature and time were 60°C and 30min, respectively. The optimization might be connected with good adsorption to DNA and thermal conductivity of ZnO nanoflower, but mechanism of the RT-LAMP reaction affected by ZnO nanoflower needs to be explored further.

  15. Griffithsin binds to the glycosylated proteins (E and prM) of Japanese encephalitis virus and inhibit its infection.

    PubMed

    Ishag, Hassan Z A; Li, Chen; Wang, Fengjuan; Mao, Xiang

    2016-04-02

    Griffithsin (GRFT) is a broad-spectrum antiviral protein against several glycosylated viruses. In our previous publication, we have shown that GRFT exerted antiviral activity against Japanese encephalitis virus (JEV) infection. Herein, we further elucidated the mechanism by which GRFT inhibits JEV infection in BHK-21 cells. In vitro experiments using Pull-down assay and Co-immunoprecipitation (CO-IP) assay showed that GRFT binds to the JEV glycosylated viral proteins, specifically the enveloped (E) and premature (prM) glycoproteins. The binding of GRFT to the JEV was competitively inhibited by increasing concentrations of mannose; in turns abolished anti-JEV activity of GRFT. We suggested that, the binding of GRFT to the glycosylated viral proteins may contribute to its anti-JEV activity. Collectively, our data indicated a possible mechanism by which GRFT exerted its anti-JEV activity. This observation suggests GRFT's potentials in the development of therapeutics against JEV or other flavivirus infection.

  16. Capsid, membrane and NS3 are the major viral proteins involved in autophagy induced by Japanese encephalitis virus.

    PubMed

    Wang, Xiujin; Hou, Lei; Du, Jige; Zhou, Lei; Ge, Xinna; Guo, Xin; Yang, Hanchun

    2015-08-05

    Japanese encephalitis virus (JEV) is an important zoonotic pathogen causing viral encephalitis in human and reproductive failure in pigs. In the present study, we first examined the autophagy induced by JEV infection in host cells, and then analyzed the JEV proteins involving in autophagy induction, and further investigated the relationship between viral protein and immunity-related GTPases M (IRGM). Our results showed that JEV infection could induce autophagy in host cells and autophagy promoted the replication of JEV in vitro; the cells transfected with individual plasmid that was expressing C, M and NS3 had a significantly higher conversion of LC3-I/II, and enhanced LC3 signals with the fluorescence punctuates accumulation which was completely co-localized with LC3 and increased number of autophagosomes-like vesicles, suggesting that C, M and NS3 are the major viral proteins involving in autophagy induction upon JEV infection; the virus titer in the cells treated by the siRNA specific for IRGM had a significant decrease, and the NS3 signals in the cells transfected with the plasmid that was expressing NS3 were completely co-localized with the IRGM signals, suggesting that the NS3 of JEV could target IRGM which may play a role in the replication of JEV. Our findings help to understand the role of autophagy in JEV and other flaviviruses infections.

  17. Antiviral activity of peptide inhibitors derived from the protein E stem against Japanese encephalitis and Zika viruses.

    PubMed

    Chen, Liman; Liu, Yang; Wang, Shaobo; Sun, Jianhong; Wang, Peilin; Xin, Qilin; Zhang, Leike; Xiao, Gengfu; Wang, Wei

    2017-02-21

    Japanese encephalitis virus (JEV) and Zika virus (ZIKV) are mosquito-borne viruses of the Flavivirus genus that cause viral encephalitis and congenital microcephaly, respectively, in humans, and thus present a risk to global public health. The envelope glycoprotein (E protein) of flaviviruses is a class II viral fusion protein that mediates host cell entry through a series of conformational changes, including association between the stem region and domain II leading to virion-target cell membrane fusion. In this study, peptides derived from the JEV E protein stem were investigated for their ability to block JEV and ZIKV infection. Peptides from stem helix 2 inhibit JEV infection with the 50% inhibitory concentration (IC50) in the nanomolar range. One of these peptides (P5) protected mice against JEV-induced lethality by decreasing viral load, while abrogating histopathological changes associated with JEV infection. We also found that P5 blocked ZIKV infection with IC50 at the micromolar level. Moreover, P5 was proved to reduce the histopathological damages in brain and testes resulting from ZIKV infection in type I and II interferon receptor-deficient (AG6) mice. These findings provide a basis for the development of peptide-based drugs against JEV and ZIKV.

  18. Beneficial role of a nonpathogenic orbi-like virus: studies on the interfering effect of M14 virus in mice and mosquitoes infected with Japanese encephalitis virus.

    PubMed

    Huang, C H; Liang, H C; Jia, F L

    1985-01-01

    M14 virus, isolated from Culex tritaeniorhynchus mosquitoes collected in a Beijing suburb, was identified as a noncytopathogenic orbi-like virus. It was found to interfere with the growth of Japanese encephalitis (JE) virus, a mosquito-borne virus which infects humans, pigs, and horses in much of Asia, including China. JE virus is transmitted by C. tritaeniorhynchus mosquitoes and causes encephalitis in humans and horses and abortion in pigs. Because it had potential as an interfering agent for the biological control of JE, the M14 virus was characterized and its interfering effect was studied in mice and in C. tritaeniorhynchus mosquitoes.

  19. Sampling Design Influences the Observed Dominance of Culex tritaeniorhynchus: Considerations for Future Studies of Japanese Encephalitis Virus Transmission.

    PubMed

    Lord, Jennifer S; Al-Amin, Hasan Mohammad; Chakma, Sumit; Alam, Mohammad Shafiul; Gurley, Emily S; Pulliam, Juliet R C

    2016-01-01

    Mosquito sampling during Japanese encephalitis virus (JEV)-associated studies, particularly in India, has usually been conducted via aspirators or light traps to catch mosquitoes around cattle, which are dead-end hosts for JEV. High numbers of Culex tritaeniorhynchus, relative to other species, have often been caught during these studies. Less frequently, studies have involved sampling outdoor resting mosquitoes. We aimed to compare the relative abundance of mosquito species between these two previously used mosquito sampling methods. From September to December 2013 entomological surveys were undertaken in eight villages in a Japanese encephalitis (JE) endemic area of Bangladesh. Light traps were used to collect active mosquitoes in households, and resting boxes and a Bina Pani Das hop cage were used near oviposition sites to collect resting mosquitoes. Numbers of humans and domestic animals present in households where light traps were set were recorded. In five villages Cx. tritaeniorhynchus was more likely to be selected from light trap samples near hosts than resting collection samples near oviposition sites, according to log odds ratio tests. The opposite was true for Cx. pseudovishnui and Armigeres subalbatus, which can also transmit JEV. Culex tritaeniorhynchus constituted 59% of the mosquitoes sampled from households with cattle, 28% from households without cattle and 17% in resting collections. In contrast Cx. pseudovishnui constituted 5.4% of the sample from households with cattle, 16% from households with no cattle and 27% from resting collections, while Ar. subalbatus constituted 0.15%, 0.38%, and 8.4% of these samples respectively. These observations may be due to differences in timing of biting activity, host preference and host-seeking strategy rather than differences in population density. We suggest that future studies aiming to implicate vector species in transmission of JEV should consider focusing catches around hosts able to transmit JEV.

  20. Sampling Design Influences the Observed Dominance of Culex tritaeniorhynchus: Considerations for Future Studies of Japanese Encephalitis Virus Transmission

    PubMed Central

    Lord, Jennifer S.; Al-Amin, Hasan Mohammad; Chakma, Sumit; Alam, Mohammad Shafiul; Gurley, Emily S.; Pulliam, Juliet R. C.

    2016-01-01

    Mosquito sampling during Japanese encephalitis virus (JEV)-associated studies, particularly in India, has usually been conducted via aspirators or light traps to catch mosquitoes around cattle, which are dead-end hosts for JEV. High numbers of Culex tritaeniorhynchus, relative to other species, have often been caught during these studies. Less frequently, studies have involved sampling outdoor resting mosquitoes. We aimed to compare the relative abundance of mosquito species between these two previously used mosquito sampling methods. From September to December 2013 entomological surveys were undertaken in eight villages in a Japanese encephalitis (JE) endemic area of Bangladesh. Light traps were used to collect active mosquitoes in households, and resting boxes and a Bina Pani Das hop cage were used near oviposition sites to collect resting mosquitoes. Numbers of humans and domestic animals present in households where light traps were set were recorded. In five villages Cx. tritaeniorhynchus was more likely to be selected from light trap samples near hosts than resting collection samples near oviposition sites, according to log odds ratio tests. The opposite was true for Cx. pseudovishnui and Armigeres subalbatus, which can also transmit JEV. Culex tritaeniorhynchus constituted 59% of the mosquitoes sampled from households with cattle, 28% from households without cattle and 17% in resting collections. In contrast Cx. pseudovishnui constituted 5.4% of the sample from households with cattle, 16% from households with no cattle and 27% from resting collections, while Ar. subalbatus constituted 0.15%, 0.38%, and 8.4% of these samples respectively. These observations may be due to differences in timing of biting activity, host preference and host-seeking strategy rather than differences in population density. We suggest that future studies aiming to implicate vector species in transmission of JEV should consider focusing catches around hosts able to transmit JEV. PMID

  1. 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

  2. MicroRNA-19b-3p Modulates Japanese Encephalitis Virus-Mediated Inflammation via Targeting RNF11

    PubMed Central

    Ashraf, Usama; Zhu, Bibo; Ye, Jing; Wan, Shengfeng; Nie, Yanru; Chen, Zheng; Cui, Min; Wang, Chong; Duan, Xiaodong; Zhang, Hao; Chen, Huanchun

    2016-01-01

    ABSTRACT Japanese encephalitis virus (JEV) can invade the central nervous system and consequently induce neuroinflammation, which is characterized by profound neuronal cell damage accompanied by astrogliosis and microgliosis. Albeit microRNAs (miRNAs) have emerged as major regulatory noncoding RNAs with profound effects on inflammatory response, it is unknown how astrocytic miRNAs regulate JEV-induced inflammation. Here, we found the involvement of miR-19b-3p in regulating the JEV-induced inflammatory response in vitro and in vivo. The data demonstrated that miR-19b-3p is upregulated in cultured cells and mouse brain tissues during JEV infection. Overexpression of miR-19b-3p led to increased production of inflammatory cytokines, including tumor necrosis factor alpha, interleukin-6, interleukin-1β, and chemokine (C-C motif) ligand 5, after JEV infection, whereas knockdown of miR-19b-3p had completely opposite effects. Mechanistically, miR-19b-3p modulated the JEV-induced inflammatory response via targeting ring finger protein 11, a negative regulator of nuclear factor kappa B signaling. We also found that inhibition of ring finger protein 11 by miR-19b-3p resulted in accumulation of nuclear factor kappa B in the nucleus, which in turn led to higher production of inflammatory cytokines. In vivo silencing of miR-19b-3p by a specific antagomir reinvigorates the expression level of RNF11, which in turn reduces the production of inflammatory cytokines, abrogates gliosis and neuronal cell death, and eventually improves the survival rate in the mouse model. Collectively, our results demonstrate that miR-19b-3p positively regulates the JEV-induced inflammatory response. Thus, miR-19b-3p targeting may constitute a thought-provoking approach to rein in JEV-induced inflammation. IMPORTANCE Japanese encephalitis virus (JEV) is one of the major causes of acute encephalitis in humans worldwide. The pathological features of JEV-induced encephalitis are inflammatory reactions and

  3. Association of IL28B rs8099917 genotype and female sex with spontaneous clearance of hepatitis C virus infection: a Japanese cross-sectional study.

    PubMed

    Ikezaki, Hiroaki; Furusyo, Norihiro; Hiramine, Satoshi; Ura, Kazuya; Mitsumoto-Kaseida, Fujiko; Takayama, Koji; Shimizu, Motohiro; Toyoda, Kazuhiro; Ogawa, Eiichi; Kainuma, Mosaburo; Murata, Masayuki; Hayashi, Jun

    2016-03-01

    Hepatitis C virus (HCV) infection is a serious global health problem. Previous studies have suggested that the interleukin 28B (IL28B) rs8099917 genotype is related to spontaneous clearance of HCV in Caucasian populations. Our objective was to investigate the association of the IL28B rs8099917 genotype with spontaneous clearance of HCV by community-dwelling Japanese. A cross-sectional community-based population study of 993 Japanese residents was conducted. Based on anti-HCV antibody and HCV RNA levels, 50 subjects were assigned to the spontaneous-clearance group, 155 to the chronic-infection group, and 788 to the control group. Logistic regression analysis was done to examine the roles of the IL28B rs8099917 genotype and sex. To analyze the interactions between these factors, an "IL28B rs809991 genotype × sex" interaction term was included in the multivariate analysis. Significantly more subjects in the spontaneous-clearance group than in the chronic-infection group had the favorable IL28B rs8099917 genotype and were female. Multivariate logistic regression analysis extracted the favorable IL28B rs8099917 TT genotype (odds ratio [OR] 9.39; 95% confidence interval [CI], 2.16-40.83, P = 0.003) and female sex (OR, 2.27; 95% CI, 1.16-4.45, P = 0.017) as factors contributing to the spontaneous clearance of HCV. No significant interaction was found between the IL28B rs8099917 genotype and sex (P for interaction = 0.428). Both the favorable IL28B rs8099917 genotype and female sex were associated with the spontaneous clearance of HCV in this Japanese population.

  4. Human Influenza Virus Infections.

    PubMed

    Peteranderl, Christin; Herold, Susanne; Schmoldt, Carole

    2016-08-01

    Seasonal and pandemic influenza are the two faces of respiratory infections caused by influenza viruses in humans. As seasonal influenza occurs on an annual basis, the circulating virus strains are closely monitored and a yearly updated vaccination is provided, especially to identified risk populations. Nonetheless, influenza virus infection may result in pneumonia and acute respiratory failure, frequently complicated by bacterial coinfection. Pandemics are, in contrary, unexpected rare events related to the emergence of a reassorted human-pathogenic influenza A virus (IAV) strains that often causes increased morbidity and spreads extremely rapidly in the immunologically naive human population, with huge clinical and economic impact. Accordingly, particular efforts are made to advance our knowledge on the disease biology and pathology and recent studies have brought new insights into IAV adaptation mechanisms to the human host, as well as into the key players in disease pathogenesis on the host side. Current antiviral strategies are only efficient at the early stages of the disease and are challenged by the genomic instability of the virus, highlighting the need for novel antiviral therapies targeting the pulmonary host response to improve viral clearance, reduce the risk of bacterial coinfection, and prevent or attenuate acute lung injury. This review article summarizes our current knowledge on the molecular basis of influenza infection and disease progression, the key players in pathogenesis driving severe disease and progression to lung failure, as well as available and envisioned prevention and treatment strategies against influenza virus infection.

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

    PubMed Central

    Takamatsu, Yuki; Morita, Kouichi

    2015-01-01

    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. PMID:25787282

  6. Regional variation in pig farmer awareness and actions regarding Japanese encephalitis in Nepal: implications for public health education.

    PubMed

    Dhakal, Santosh; Joshi, Durga Datt; Ale, Anita; Sharma, Minu; Dahal, Meena; Shah, Yogendra; Pant, Dhan Kumar; Stephen, Craig

    2014-01-01

    Japanese encephalitis (JE) is a mosquito-borne zoonotic disease that has pigs as the major amplifying hosts. It is the most important cause of viral encephalitis in people in Nepal and is spreading in its geographic distribution in that country. Pig farming is increasing in Nepal due to reducing cultural biases against pigs and government programs to support pig farming for poverty alleviation. Major strategies for JE prevention and control include education, vector control, and immunization of people and pigs. This study used a survey of 400 pig farmers in 4 areas of Nepal with different JE and pig farming histories to explore regional variations in farmer awareness and actions towards JE, the association of awareness and actions with farm and farmer variables, and the implications of these associations for public health education. Exposure to JE risk factors was common across pig farms and pig farming districts but there were significant district level differences in knowledge and practices related to on-farm JE risk reduction. Social factors such as literacy, gender, and cultural practices were associated with farmer attitudes, knowledge and practices for JE control. JE vaccine uptake was almost non-existent and mosquito control steps were inconsistently applied across all 4 districts. Income was not a determining factor of the differences, but all farmers were very poor. The low uptake of vaccine and lack of infrastructure or financial capacity to house pigs indoors or away from people suggest that farmer personal protection should be a priority target for education in Nepal. This study re-enforces the need to attack root causes of people's personal disease prevention behaviours and take into account local variation in needs and capacities when designing health or agriculture education programs.

  7. Seasonal abundance & role of predominant Japanese encephalitis vectors Culex tritaeniorhynchus & Cx. gelidus Theobald in Cuddalore district, Tamil Nadu

    PubMed Central

    Ramesh, D.; Muniaraj, M.; Samuel, P. Philip; Thenmozhi, V.; Venkatesh, A.; Nagaraj, J.; Tyagi, B.K.

    2015-01-01

    Background & objectives: Japanese encephalitis (JE) is the leading cause of viral encephalitis in Asia. The first major JE outbreak occurred in 1978 and since 1981 several outbreaks had been reported in the Cuddalore district (erstwhile South Arcot), Tamil Nadu, India. Entomological monitoring was carried out during January 2010 - March 2013, to determine the seasonal abundance and transmission dynamics of the vectors of JE virus, with emphasis on the role of Culex tritaeniorhynchus and Cx. gelidus. Methods: Mosquito collections were carried out fortnightly during dusk hours in three villages viz. Soundara Solapuram, Pennadam, Erappavur of Cuddalore district. Mosquitoes were collected during dusk for a period of one hour in and around the cattle sheds using oral aspirator and torch light. The collected mosquitoes were later identified and pooled to detect JE virus (JEV) infection by enzyme linked immunosorbent assay (ELISA). Results: A total of 46,343 mosquitoes comprising of 25 species and six genera were collected. Species composition included viz, Cx. tritaeniorhynchus (46.26%), Cx. gelidus (43.12%) and other species (10.62%). A total of 17,678 specimens (403 pools) of Cx. gelidus and 14,358 specimens (309 pools) of Cx. tritaeniorhynchus were tested, of which 12 pools of Cx. gelidus and 14 pools of Cx. tritaeniorhynchus were positive for JE virus antigen. The climatic factors were negatively correlated with minimum infection rate (MIR) for both the species, except mean temperature (P<0.05) for Cx. gelidus. Interpretation & conclusions: High abundance of Cx. tritaeniorhynchus and Cx. gelidus was observed compared to other mosquito species in the study area. Detection of JEV antigen in the two species confirmed the maintenance of virus. Appropriate vector control measures need to be taken to reduce the vector abundance. PMID:26905238

  8. Respiratory syncytial virus infection in infants with acute leukemia: a retrospective survey of the Japanese Pediatric Leukemia/Lymphoma Study Group.

    PubMed

    Hatanaka, Michiki; Miyamura, Takako; Koh, Katsuyoshi; Taga, Takashi; Tawa, Akio; Hasegawa, Daisuke; Kajihara, Ryosuke; Adachi, Souichi; Ishii, Eiichi; Tomizawa, Daisuke

    2015-12-01

    Respiratory syncytial virus (RSV) can cause life-threatening complications of lower respiratory tract infection (LRTI) in young children with malignancies, but reports remain limited. We performed a retrospective nationwide survey to clarify the current status of RSV disease among infants with hematological malignancies. Clinical course, treatment, and outcome of patients with hematological malignancies who suffered from RSV infections at the age of <24 months during anti-tumor therapy from April 2006 to March 2009 were investigated by sending a questionnaire to all member institutions of the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG). Twelve patients with acute leukemia were identified as having experienced RSV disease. The primary diseases were acute myeloid leukemia (n = 8) and acute lymphoblastic leukemia (n = 4). RSV infection occurred pre- or during induction therapy (n = 8) and during consolidation therapy (n = 4). Eight patients developed LRTI, four of whom had severe pneumonia or acute respiratory distress syndrome; these four patients died despite receiving intensive care. In our survey, the prognosis of RSV disease in pediatric hematological malignancies was poor, and progression of LRTI in particular was associated with high mortality. In the absence of RSV-specific therapy, effective prevention and treatment strategies for severe RSV disease must be investigated.

  9. Suppression subtractive hybridization coupled with microarray analysis to examine differential expression of genes in Japanese flounder Paralichthys olivaceus leucocytes during Edwardsiella tarda and viral hemorrhagic septicemia virus infection.

    PubMed

    Matsuyama, Tomomasa; Fujiwara, Atushi; Takano, Tomokazu; Nakayasu, Chihaya

    2011-10-01

    Transcriptional changes in the peripheral blood leucocytes (PBL) of Japanese flounder Paralichthys olivaceus challenged by Edwardsiella tarda and viral hemorrhagic septicemia virus (VHSV) were investigated using suppression subtractive hybridization (SSH) coupled with cDNA microarray analysis. First, we constructed an SSH cDNA library using mRNA samples isolated from PBL of P. olivaceus that had been experimentally infected with E. tarda. We then examined the transcriptional changes occurring in the PBL due to E. tarda and VHSV infection using a cDNA microarray produced using clones produced from the SSH library. A total of 565 and 180 cDNA sequences corresponding to mRNA species that are either up- or down-regulated by E. tarda infection were isolated by SSH. While host gene expression responses in response to E. tarda and VHSV infection share several response elements, distinct patterns of gene expression were also observed. Specifically, E. tarda infection enhanced the expression of cell adhesion molecules while VHSV enhanced the expression of interferon and proteasome-related genes. In challenge trials of the two infectious agents, expression profiles of chemokines were also observed to differ. The results indicated that distinguishing between viral and bacterial infection is possible based on the RNA expression profiles of PBL from infected fish.

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

    PubMed Central

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

    2017-01-01

    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. PMID:28322689

  11. 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.

  12. Development of electrochemical immunosensors based on different serum antibody immobilization methods for detection of Japanese encephalitis virus

    NASA Astrophysics Data System (ADS)

    Tran, Quang Huy; Hanh Nguyen, Thi Hong; Mai, Anh Tuan; Thuy Nguyen, Thi; Khue Vu, Quang; Nga Phan, Thi

    2012-03-01

    This paper describes the development of electrochemical immunosensors based on human serum antibodies with different immobilization methods for detection of Japanese encephalitis virus (JEV). Human serum containing anti-JEV antibodies was used to immobilize onto the surface of silanized interdigitated electrodes by four methods: direct adsorption (APTES-serum), covalent binding with a cross linker of glutaraldehyde (APTES-GA-serum), covalent binding with a cross linker of glutaraldehyde combined with anti-human IgG (APTES-GA-anti-HIgG-serum) and covalent binding with a cross linker of glutaraldehyde combined with a bioaffinity of protein A (APTES-GA-PrA-serum). Atomic force microscopy was used to verify surface characteristics of the interdigitated electrodes before and after treatment with serum antibodies. The output signal of the immunosensors was measured by the change of conductivity resulting from the specific binding of JEV antigens and serum antibodies immobilized on the electrodes, with the help of horseradish peroxidase (HRP)-labeled secondary antibody against JEV. The results showed that the APTES-GA-PrA-serum method provided the highest signal of the electrochemical immunosensor for detection of JEV antigens, with the linear range from 25 ng ml-1 to 1 μg ml-1, and the limit of detection was about 10 ng ml-1. This study shows a potential development of novel electrochemical immunosensors applied for virus detection in clinical samples in case of possible outbreaks.

  13. The Involvement of Microtubules and Actin during the Infection of Japanese Encephalitis Virus in Neuroblastoma Cell Line, IMR32

    PubMed Central

    Henry Sum, Magdline Sia

    2015-01-01

    The role of the cytoskeleton, actin, and microtubules were examined during the process of Japanese encephalitis (JEV) infection in a human neuroblastoma cell line, IMR32. Cytochalasin D and nocodazole were used to depolymerise the cellular actin and microtubules, respectively, in order to study the effect of JEV infection in the cell. This study shows that depolymerisation of the actin cytoskeleton at early process of infection inhibits JEV infection in the cell; however infection was not inhibited when depolymerisation occurred at the later stage of infection. The microtubules, on the other hand, are required at 2 points in infection. The antigen production in the cells was inhibited when the infected cells were treated at time up to 2 hours after inoculation and there was no significant effect at later times, while the viable virus released continued to be affected until 10 hours after inoculation. In conclusion, infection of JEV in IMR32 cells required actin to facilitate early process in infection and the microtubular network is utilised as the transport system to the virus replication site and the release of mature virus. PMID:25705678

  14. Survey of the antibody against japanese encephalitis virus in Ryukyu wild boars (Sus scrofa riukiuanus) in Okinawa, Japan.

    PubMed

    Nidaira, Minoru; Taira, Katsuya; Itokazu, Kiyomasa; Kudaka, Jun; Nakamura, Masaji; Ohno, Atsusi; Takasaki, Tomohiko

    2007-09-01

    Serum specimens were collected from 99 wild boars in the Northern area of the main Okinawa Island and from 27 wild boars on Iriomote Island in Okinawa Prefecture from 1997 to 2005. Sera were tested for Japanese encephalitis virus (JEV) antibody by hemagglutination inhibition assay and IgG enzyme-linked immunosorbent assay. Sixty-four samples (64.6%) in the Northern area and 1 sample (3.7%) from Iriomote Island were positive for the JEV antibody. The difference in seroprevalence between the Northern area and Iriomote Island was statistically significant (P < 0.01, chi2 test). This difference may be due to the lack of a pig farm on Iriomote Island, whereas wild boars in the Northern area may be infected with JEV, amplified on pig farms. It is likely that there has recently been an increase in the number of wild boars living close to humans in certain areas of Japan. This in turn increases the possibility that wild boars are infected with JEV, which is amplified on pig farms, and these infected animals may play a role in carrying JEV to other regions of the country.

  15. Standardization of serum neutralization assay of Japanese encephalitis virus (Nakayama NIH strain) on BHK-21 (Cl-13) cell line.

    PubMed

    Singh, S; Sharma, M; Kumar, S; Gowal, D

    2015-09-01

    Potency testing of Japanese encephalitis (JE) vaccine has been a complex process since its inception. To overcome difficulties encountered therein, an alternative assay, serum neutralization test (SNT), using Baby Hamster Kidney 21 cell line, has been standardized. The antibody response generated against JE vaccine was quantified and the assay was found to be sensitive and specific enough with significant accuracy and precision. On analysis of cell count, a cell concentration of 1.5 x 104 was selected as the optimum, since concentrations above and below this resulted in problems of confluent monolayer formation and incomplete monolayer formation. Incubation time has also been standardized for measuring cytopathic effect (CPE). Out of the four different time points selected, 90 min was found to be adequate for 50% reduction in the amount of CPE. The accuracy of SNT assay is explained in terms of fiducial limits at 95% level. Inter- and intra-assay reproducibility testing was also performed. A comparison of potency of JE vaccine by plaque reduction neutralization test (PRNT) and SNT method was conducted and it was found that SNT can be a reliable approach for estimating the potency of JE vaccine. The results of this study throw a light on the utility of SNT assay for the potency estimation of JE vaccine in routine practice.

  16. Structure-based discovery of two antiviral inhibitors targeting the NS3 helicase of Japanese encephalitis virus

    PubMed Central

    Fang, Jin’e; Li, Huan; Kong, Dexin; Cao, Shengbo; Peng, Guiqing; Zhou, Rui; Chen, Huanchun; Song, Yunfeng

    2016-01-01

    Japanese encephalitis virus (JEV) is a flavivirus that threatens more than half of the world’s population. Vaccination can prevent the disease, but no specific antiviral drug is yet available for clinical therapy, and the death rate caused by JEV can reach as high as 60%. The C-terminus of non-structural protein 3 (NS3) of flavivirus encodes helicase and has been identified as a potential drug target. In this study, high throughput molecular docking was employed to identify candidate JEV NS3 helicase inhibitors in a commercial library containing 250,000 compounds. Forty-one compounds were then tested for their ability to inhibit NS3 activity. Two compounds inhibited unwinding activity strongly but had no effect on the ATPase activity of the protein. Western blots, IFA, and plaque reduction assays demonstrated that both compounds inhibited the virus in cell culture. The EC50s of the two compounds were 25.67 and 23.50 μM, respectively. Using simulated docking, the two compounds were shown to bind and block the NS3 RNA unwinding channel, consistent with the results of the enzyme inhibition tests. The atoms participating in intramolecular interaction were identified to facilitate future compound optimization. PMID:27679979

  17. Prevalence of antibodies to Japanese encephalitis virus among inhabitants in Java Island, Indonesia, with a small pig population.

    PubMed

    Konishi, Eiji; Sakai, Yohei; Kitai, Yoko; Yamanaka, Atsushi

    2009-05-01

    Japanese encephalitis virus (JEV) is maintained through a transmission cycle between amplifier swine and vector mosquitoes in a peridomestic environment. Thus, studies on natural JEV activities in an environment with a small size of pig population have been limited. Here, we surveyed antibodies against JEV in inhabitants of Jakarta and Surabaya located in Java Island (Indonesia), which has a small swine population. Overall, 2.2% of 1,211 sera collected in Jakarta and 1.8% of 1,751 sera collected in Surabaya had neutralizing antibody titers of >or= 1:160 (90% plaque reduction). All the samples with titers of >or= 1:160 against JEV were also examined for neutralizing antibodies against each of four dengue viruses to confirm that JEV antibody prevalences obtained in the present survey were not attributable to serologic cross-reactivities among flaviviruses distributed in Java. These results indicated that people in Java Island are exposed to natural JEV infections despite a small swine population.

  18. Aloe-emodin is an interferon-inducing agent with antiviral activity against Japanese encephalitis virus and enterovirus 71.

    PubMed

    Lin, Cheng-Wen; Wu, Chia-Fang; Hsiao, Nai-Wan; Chang, Ching-Yao; Li, Shih-Wein; Wan, Lei; Lin, Ying-Ju; Lin, Wei-Yong

    2008-10-01

    In this study, aloe-emodin was identified as a potential interferon (IFN)-inducer by screening compounds from Chinese herbal medicine. Aloe-emodin showed low cytotoxicity to human HL-CZ promonocyte cells and TE-671 medulloblastoma cells and significantly activated interferon-stimulated response element (ISRE) and gamma-activated sequence (GAS)-driven cis-reporting systems. Moreover, aloe-emodin upregulated expression of IFN-stimulated genes such as dsRNA-activated protein kinase and 2',5'-oligoisoadenylate synthase. Aloe-emodin resulted in significant activation of nitric oxide production. The antiviral activity of aloe-emodin against Japanese encephalitis virus (JEV) and enterovirus 71 (EV71) was evaluated using dose- and time-dependent plaque reduction assays in HL-CZ cells and TE-671 cells. The 50% inhibitory concentration (IC(50)) of aloe-emodin ranged from 0.50microg/mL to 1.51microg/mL for JEV and from 0.14microg/mL to 0.52microg/mL for EV71. Aloe-emodin showed clearly potent virus inhibitory abilities and achieved high therapeutic indices, in particular for HL-CZ cells. Therefore, the study demonstrated dose- and time-dependent actions of aloe-emodin on the inhibition of JEV and EV71 replication via IFN signalling responses.

  19. Comparison of performance of serum and plasma in panbio dengue and Japanese encephalitis virus enzyme-linked immunosorbent assays.

    PubMed

    Blacksell, Stuart D; Lee, Sue J; Chanthongthip, Anisone; Taojaikong, Thaksinaporn; Thongpaseuth, Soulignasack; Hübscher, Tanja; Newton, Paul N

    2012-09-01

    We examined the comparative performance of serum and plasma (in dipotassium EDTA) in Panbio Dengue enzyme-linked immunosorbent assays (ELISAs) for detection of non-structural protein 1 (NS1), IgM, and IgG, and a dengue/Japanese encephalitis virus (JEV) combination IgM ELISA in a prospective series of 201 patients with suspected dengue in Laos. Paired comparisons of medians from serum and plasma samples were not significantly different for Dengue IgM, and NS1 which had the highest number of discordant pairs (both 2%; P = 0.13 and P = 0.25, respectively). Comparison of qualitative final diagnostic interpretations for serum and plasma samples were not significantly different: only 1.5% (3 of 201 for Dengue/JEV IgM and Dengue IgG) and 2.0% (4 of 201; IgM and NS1) showed discordant pairs. These results demonstrate that plasma containing EDTA is suitable for use in these ELISAs.

  20. Green synthesis and characterization of silver nanoparticles fabricated using Anisomeles indica: Mosquitocidal potential against malaria, dengue and Japanese encephalitis vectors.

    PubMed

    Govindarajan, Marimuthu; Rajeswary, Mohan; Veerakumar, Kaliyan; Muthukumaran, Udaiyan; Hoti, S L; Benelli, Giovanni

    2016-02-01

    Mosquitoes (Diptera: Culicidae) represent a key threat for millions of people worldwide, since they act as vectors for devastating parasites and pathogens. In this scenario, eco-friendly control tools against mosquito vectors are a priority. Green synthesis of silver nanoparticles (AgNP) using a cheap, aqueous leaf extract of Anisomeles indica by reduction of Ag(+) ions from silver nitrate solution has been investigated. Bio-reduced AgNP were characterized by UV-visible spectrophotometry, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive spectroscopy (EDX) and X-ray diffraction analysis (XRD). The acute toxicity of A. indica leaf extract and biosynthesized AgNP was evaluated against larvae of the malaria vector Anopheles subpictus, the dengue vector Aedes albopictus and the Japanese encephalitis vector Culex tritaeniorhynchus. Both the A. indica leaf extract and AgNP showed dose dependent larvicidal effect against all tested mosquito species. Compared to the leaf aqueous extract, biosynthesized AgNP showed higher toxicity against An. subpictus, Ae. albopictus, and Cx. tritaeniorhynchus with LC50 values of 31.56, 35.21 and 38.08 μg/mL, respectively. Overall, this study firstly shed light on the mosquitocidal potential of A. indica, a potential bioresource for rapid, cheap and effective AgNP synthesis.

  1. Distinct usage of three C-type lectins by Japanese encephalitis virus: DC-SIGN, DC-SIGNR, and LSECtin.

    PubMed

    Shimojima, Masayuki; Takenouchi, Atsushi; Shimoda, Hiroshi; Kimura, Naho; Maeda, Ken

    2014-08-01

    Infection with West Nile virus and dengue virus, two mosquito-borne flaviviruses, is enhanced by two calcium-dependent lectins: dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN), and its related molecule (DC-SIGNR). The present study examined the relationship between Japanese encephalitis virus (JEV) infection and three lectins: DC-SIGN, DC-SIGNR, and liver sinusoidal endothelial cell lectin (LSECtin). Expression of DC-SIGNR resulted in robust JEV proliferation in a lymphoid cell line, Daudi cells, which was otherwise non-permissive to infection. DC-SIGN expression caused moderate JEV proliferation, with effects that varied according to the cells in which JEV was prepared. LSECtin expression had comparatively minor, but consistent, effects, in all cell types used in JEV preparation. While DC-SIGN/DC-SIGNR-mediated JEV infection was inhibited by yeast mannan, LSECtin-mediated infection was inhibited by N-acetylglucosamine β1-2 mannose. Although involvement of DC-SIGN/DC-SIGNR in infection seems to be a common characteristic, this is the first report on usage of LSECtin in mosquito-borne flavivirus infection.

  2. Characterization of the GXXXG motif in the first transmembrane segment of Japanese encephalitis virus precursor membrane (prM) protein.

    PubMed

    Lin, Ying-Ju; Peng, Jia-Guan; Wu, Suh-Chin

    2010-05-24

    The interaction between prM and E proteins in flavivirus-infected cells is a major driving force for the assembly of flavivirus particles. We used site-directed mutagenesis to study the potential role of the transmembrane domains of the prM proteins of Japanese encephalitis virus (JEV) in prM-E heterodimerization as well as subviral particle formation. Alanine insertion scanning mutagenesis within the GXXXG motif in the first transmembrane segment of JEV prM protein affected the prM-E heterodimerization; its specificity was confirmed by replacing the two glycines of the GXXXG motif with alanine, leucine and valine. The GXXXG motif was found to be conserved in the JEV serocomplex viruses but not other flavivirus groups. These mutants with alanine inserted in the two prM transmembrane segments all impaired subviral particle formation in cell cultures. The prM transmembrane domains of JEV may play importation roles in prM-E heterodimerization and viral particle assembly.

  3. Bivalent vaccine platform based on Japanese encephalitis virus (JEV) elicits neutralizing antibodies against JEV and hepatitis C virus.

    PubMed

    Saga, Ryohei; Fujimoto, Akira; Watanabe, Noriyuki; Matsuda, Mami; Hasegawa, Makoto; Watashi, Koichi; Aizaki, Hideki; Nakamura, Noriko; Tajima, Shigeru; Takasaki, Tomohiko; Konishi, Eiji; Kato, Takanobu; Kohara, Michinori; Takeyama, Haruko; Wakita, Takaji; Suzuki, Ryosuke

    2016-06-27

    Directly acting antivirals recently have become available for the treatment of hepatitis C virus (HCV) infection, but there is no prophylactic vaccine for HCV. In the present study, we took advantage of the properties of Japanese encephalitis virus (JEV) to develop antigens for use in a HCV vaccine. Notably, the surface-exposed JEV envelope protein is tolerant of inserted foreign epitopes, permitting display of novel antigens. We identified 3 positions that permitted insertion of the HCV E2 neutralization epitope recognized by HCV1 antibody. JEV subviral particles (SVP) containing HCV-neutralization epitope (SVP-E2) were purified from culture supernatant by gel chromatography. Sera from mice immunized with SVP-E2 inhibited infection by JEV and by trans-complemented HCV particles (HCVtcp) derived from multi-genotypic viruses, whereas sera from mice immunized with synthetic E2 peptides did not show any neutralizing activity. Furthermore, sera from mice immunized with SVP-E2 neutralized HCVtcp with N415K escape mutation in E2. As with the SVP-E2 epitope-displaying particles, JEV SVPs with HCV E1 epitope also elicited neutralizing antibodies against HCV. Thus, this novel platform harboring foreign epitopes on the surface of the particle may facilitate the development of a bivalent vaccine against JEV and other pathogens.

  4. Bivalent vaccine platform based on Japanese encephalitis virus (JEV) elicits neutralizing antibodies against JEV and hepatitis C virus

    PubMed Central

    Saga, Ryohei; Fujimoto, Akira; Watanabe, Noriyuki; Matsuda, Mami; Hasegawa, Makoto; Watashi, Koichi; Aizaki, Hideki; Nakamura, Noriko; Tajima, Shigeru; Takasaki, Tomohiko; Konishi, Eiji; Kato, Takanobu; Kohara, Michinori; Takeyama, Haruko; Wakita, Takaji; Suzuki, Ryosuke

    2016-01-01

    Directly acting antivirals recently have become available for the treatment of hepatitis C virus (HCV) infection, but there is no prophylactic vaccine for HCV. In the present study, we took advantage of the properties of Japanese encephalitis virus (JEV) to develop antigens for use in a HCV vaccine. Notably, the surface-exposed JEV envelope protein is tolerant of inserted foreign epitopes, permitting display of novel antigens. We identified 3 positions that permitted insertion of the HCV E2 neutralization epitope recognized by HCV1 antibody. JEV subviral particles (SVP) containing HCV-neutralization epitope (SVP-E2) were purified from culture supernatant by gel chromatography. Sera from mice immunized with SVP-E2 inhibited infection by JEV and by trans-complemented HCV particles (HCVtcp) derived from multi-genotypic viruses, whereas sera from mice immunized with synthetic E2 peptides did not show any neutralizing activity. Furthermore, sera from mice immunized with SVP-E2 neutralized HCVtcp with N415K escape mutation in E2. As with the SVP-E2 epitope-displaying particles, JEV SVPs with HCV E1 epitope also elicited neutralizing antibodies against HCV. Thus, this novel platform harboring foreign epitopes on the surface of the particle may facilitate the development of a bivalent vaccine against JEV and other pathogens. PMID:27345289

  5. Recognition of helper T cell epitopes in envelope (E) glycoprotein of Japanese encephalitis, west Nile and Dengue viruses.

    PubMed

    Kutubuddin, M; Kolaskar, A S; Galande, S; Gore, M M; Ghosh, S N; Banerjee, K

    1991-01-01

    Helper T (Th) cell antigenic sites were predicted from the primary amino acid sequence (approximately 500 in length) of the envelope (E) glycoprotein (gp) of Japanese encephalitis (JE), West Nile (WN) and Dengue (DEN) I-IV flaviviruses. Prediction of Th epitopes was done by analyzing the occurrence of amphipathic segments, Rothbard-Taylor tetra/pentamer motifs and presence of alpha helix-preferring amino acids. The simultaneous occurrence of all these parameters in segments of E gp were used as criteria for prediction as Th epitopes. Only one cross reactive epitope was predicted in the C-terminal region of the E gp predicted segments of all flaviviruses analyzed. This region is one of the longest amphipathic stretch (approximately from 420 to 455) and also has a fairly large amphipathic score. Based on the predicted findings three selected peptides were synthesized and analyzed for their ability to induce in vitro T cell proliferative response in different inbred strains of mice (Balb/c, C57BL6, C3H/HeJ). Synthetic peptide I and II prepared from C-terminal region gave a cross reactive response to JE, WN and Den-II in Balb/c and C3H/HeJ mice. Synthetic peptide III prepared from N-terminal region gave a proliferative response to DEN-II in Balb/c strain only, indicating differential antigen presentation.

  6. A Preliminary Study to Forecast Japanese Encephalitis Vector Abundance in Paddy Growing Area, with the Aid of Radar Satellite Images.

    PubMed

    Raju, K Hari Kishan; Sabesan, Shanmugavelu; Rajavel, Aladu Ramakrishnan; Subramanian, Swaminathan; Natarajan, Ramalingam; Thenmozhi, Velayutham; Tyagi, Brij Kishore; Jambulingam, Purushothaman

    2016-02-01

    Vector mosquitoes of Japanese encephalitis (JE) breed mostly in rice fields, and human cases occur scattered over extended rural rice-growing areas. From this, one may surmise an ecological connection with the irrigation facilities and paddy cultivation. Furthermore, it has been hypothesized that a particular stage of paddy growth is a premonitory sign that can lead to a markedly increased population of the vector mosquitoes. The present study aimed to forecast the vector abundance by monitoring the paddy growth using remote sensing and geographical information systems. The abundance of the JE vector Culex tritaeniorhynchus peaked when the paddy crop was at its heading stage and dipped when the crop reached the maturing stage. A significant positive correlation was observed between paddy growth and adult density (r = 0.73, p < 0.008). The sigma naught values (σ0) derived from satellite images of paddy fields ranged from -18.3 (during transplantation stage) to approximately -10 (during the noncultivation period). A significant positive correlation was observed between σ0 and paddy growth stages (r = 0.87, p < 0.05) and adult vector density (r = 0.74, p = 0.04). The σ0 value observed during the vegetative and flowering stages of paddy growth ranged from -17.6 to -17.16, at which period the vector density started building up. This could be the spectral signature that denotes the "risk," following which a high vector abundance is expected during heading stage of the paddy.

  7. Characterization of immune responses induced by inactivated, live attenuated and DNA vaccines against Japanese encephalitis virus in mice.

    PubMed

    Li, Jieqiong; Chen, Hui; Wu, Na; Fan, Dongying; Liang, Guodong; Gao, Na; An, Jing

    2013-08-28

    Vaccination is the most effective countermeasure for protecting individuals from Japanese encephalitis virus (JEV) infection. There are two types of JEV vaccines currently used in China: the Vero cell-derived inactivated vaccine and the live attenuated vaccine. In this study, we characterized the immune response and protective efficacy induced in mice by the inactivated vaccine, live attenuated vaccine and the DNA vaccine candidate pCAG-JME, which expresses JEV prM-E proteins. We found that the live attenuated vaccine conferred 100% protection and resulted in the generation of high levels of specific anti-JEV antibodies and cytokines. The pCAG-JME vaccine induced protective immunity as well as the live attenuated vaccine. Unexpectedly, immunization with the inactivated vaccine only induced a limited immune response and partial protection, which may be due to the decreased activity of dendritic cells and the expansion of CD4+CD25+Foxp3+ regulatory T cells observed in these mice. Altogether, our results suggest that the live attenuated vaccine is more effective in providing protection against JEV infection than the inactivated vaccine and that pCAG-JME will be a potential JEV vaccine candidate.

  8. Viruses infecting marine molluscs.

    PubMed

    Arzul, Isabelle; Corbeil, Serge; Morga, Benjamin; Renault, Tristan

    2017-02-09

    Although a wide range of viruses have been reported in marine molluscs, most of these reports rely on ultrastructural examination and few of these viruses have been fully characterized. The lack of marine mollusc cell lines restricts virus isolation capacities and subsequent characterization works. Our current knowledge is mostly restricted to viruses affecting farmed species such as oysters Crassostrea gigas, abalone Haliotis diversicolor supertexta or the scallop Chlamys farreri. Molecular approaches which are needed to identify virus affiliation have been carried out for a small number of viruses, most of them belonging to the Herpesviridae and birnaviridae families. These last years, the use of New Generation Sequencing approach has allowed increasing the number of sequenced viral genomes and has improved our capacity to investigate the diversity of viruses infecting marine molluscs. This new information has in turn allowed designing more efficient diagnostic tools. Moreover, the development of experimental infection protocols has answered some questions regarding the pathogenesis of these viruses and their interactions with their hosts. Control and management of viral diseases in molluscs mostly involve active surveillance, implementation of effective bio security measures and development of breeding programs. However factors triggering pathogen development and the life cycle and status of the viruses outside their mollusc hosts still need further investigations.

  9. Antiviral Activity of a Novel Compound CW-33 against Japanese Encephalitis Virus through Inhibiting Intracellular Calcium Overload

    PubMed Central

    Huang, Su-Hua; Lien, Jin-Cherng; Chen, Chao-Jung; Liu, Yu-Ching; Wang, Ching-Ying; Ping, Chia-Fong; Lin, Yu-Fong; Huang, An-Cheng; Lin, Cheng-Wen

    2016-01-01

    Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, has five genotypes (I, II, III, IV, and V). JEV genotype I circulates widely in some Asian countries. However, current JEV vaccines based on genotype III strains show low neutralizing capacities against genotype I variants. In addition, JE has no specific treatment, except a few supportive treatments. Compound CW-33, an intermediate synthesized derivative of furoquinolines, was investigated for its antiviral activities against JEV in this study. CW-33 exhibited the less cytotoxicity to Syrian baby hamster kidney (BHK-21) and human medulloblastoma (TE761) cells. CW-33 dose-dependently reduced the cytopathic effect and apoptosis of JEV-infected cells. Supernatant virus yield assay pinpointed CW-33 as having potential anti-JEV activity with IC50 values ranging from 12.7 to 38.5 μM. Time-of-addition assay with CW-33 indicated that simultaneous and post-treatment had no plaque reduction activity, but continuous and simultaneous treatments proved to have highly effective antiviral activity, with IC50 values of 32.7 and 48.5 μM, respectively. CW-33 significantly moderated JEV-triggered Ca2+ overload, which correlated with the recovery of mitochondria membrane potential as well as the activation of Akt/mTOR and Jak/STAT1 signals in treated infected cells. Phosphopeptide profiling by LC-MS/MS revealed that CW-33 upregulated proteins from the enzyme modulator category, such as protein phosphatase inhibitor 2 (I-2), Rho GTPase-activating protein 35, ARF GTPase-activating protein GIT2, and putative 3-phosphoinositide-dependent protein kinase 2. These enzyme modulators identified were associated with the activation of Akt/mTOR and Jak/STAT1 signals. Meanwhile, I-2 treatment substantially inhibited the apoptosis of JEV-infected cells. The results demonstrated that CW-33 exhibited a significant potential in the development of anti-JEV agents. PMID:27563890

  10. The Spatio-temporal Distribution of Japanese Encephalitis Cases in Different Age Groups in Mainland China, 2004 – 2014

    PubMed Central

    Wang, Huanyu; Song, Miao; Li, Minghua; Fu, Shihong; Lv, Zhi; He, Ying; Lei, Wenwen; Wang, Bin; Lu, Xiaoqing; Liang, Guodong

    2016-01-01

    Background Japanese encephalitis (JE) is very prevalent in China, but the incidence of JE among children has been greatly reduced by extensive promotion of vaccinations. The incidence of JE among adults, however, has increased in some parts of China. Methods/Principal Findings Data on JE in mainland China, in terms of incidence, gender, and age, were collected between 2004 and 2014. We conducted spatial and temporal analyses on data from different age groups. Generally, children aged 0–15 years still represent the major population of JE cases in China, despite the gradual decrease in incidence over years. However, the incidence of JE among adults in several provinces is notably higher than the national average, especially during the epidemic waves in 2006, 2009, and 2013. The JE cases in the 0–15-year-old group are distributed mainly in the area south of the Yangtze River, with peak incidence occurring from July to September. In the adult group, especially for those over 40 years old, the JE cases are concentrated mainly in the area north of the Yangtze River. JE incidence in the adult group in September and October is significantly greater compared to the other groups. Further analysis using Local Indicators of Spatial Association (LISA) reveals that the distribution of adult JE cases in the six provinces north of the Yangtze River, between north 30–35° latitude and east 110–130° longitude, is a hotspot for adult JE cases. Conclusions/Significance The rate of JE case increase for adults is much greater than for children and has become a public health issue. Therefore, studies on the necessity and feasibility of vaccinating adults who live in JE-endemic areas, but have never been vaccinated for JE, should become a new focus of JE prevention in the future. PMID:27050414

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

    PubMed

    Lee, Eun Ju; Cha, Go-Woon; 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 (1.3%) subjects were found to have been recently infected by the virus [corrected]. 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.

  12. [West Nile virus infection].

    PubMed

    Pérez Ruiz, Mercedes; Gámez, Sara Sanbonmatsu; Clavero, Miguel Angel Jiménez

    2011-12-01

    West Nile virus (WNV) is an arbovirus usually transmitted by mosquitoes. The main reservoirs are birds, although the virus may infect several vertebrate species, such as horses and humans. Up to 80% of human infections are asymptomatic. The most frequent clinical presentation is febrile illness, and neuroinvasive disease can occur in less than 1% of cases. Spain is considered a high-risk area for the emergence of WNV due to its climate and the passage of migratory birds from Africa (where the virus is endemic). These birds nest surrounding wetlands where populations of possible vectors for the virus are abundant. Diagnosis of human neurological infections can be made by detection of IgM in serum and/or cerebrospinal fluid samples, demonstration of a four-fold increase in IgG antibodies between acute-phase and convalescent-phase serum samples, or by detection of viral genome by reverse transcription-polymerase chain reaction (especially useful in transplant recipients). Since WNV is a biosafety level 3 agent, techniques that involve cell culture are restricted to laboratories with this level of biosafety, such as reference laboratories. The National Program for the Surveillance of WNV Encephalitis allows the detection of virus circulation among birds and vectors in areas especially favorable for the virus, such as wetlands, and provides information for evaluation of the risk of disease in horses and humans.

  13. Neonatal herpes simplex virus infections.

    PubMed

    Pinninti, Swetha G; Kimberlin, David W

    2013-04-01

    Neonatal herpes simplex virus infections are uncommon, but because of the morbidity and mortality associated with the infection they are often considered in the differential diagnosis of ill neonates. The use of polymerase chain reaction for diagnosis of central nervous system infections and the development of safe and effective antiviral therapy has revolutionized the diagnosis and management of these infants. Initiation of long-term antiviral suppressive therapy in these infants has led to significant improvement in morbidity. This article summarizes the epidemiology of neonatal herpes simplex virus infections and discusses clinical presentation, diagnosis, management, and follow up of infants with neonatal herpes disease.

  14. Avian Influenza A Virus Infections in Humans

    MedlinePlus

    ... this? Submit Button Past Newsletters Avian Influenza A Virus Infections in Humans Language: English Español Recommend ... with Avian Influenza A Viruses Avian Influenza A Virus Infections in Humans Although avian influenza A viruses ...

  15. Adverse events after Japanese encephalitis vaccination: review of post-marketing surveillance data from Japan and the United States. The VAERS Working Group.

    PubMed

    Takahashi, H; Pool, V; Tsai, T F; Chen, R T

    2000-07-01

    We determined the reporting rates for adverse events following the administration of inactivated mouse-brain derived Japanese encephalitis vaccine (JEV) based on post-marketing surveillance data from Japan and the United States. The rate of total adverse events per 100,000 doses was 2.8 in Japan and 15.0 in the United States. In Japan, 17 neurological disorders were reported from April 1996 to October 1998 for a rate of 0.2 per 100,000 doses. In the United States, no serious neurological adverse events temporally associated with JEV were reported from January 1993 to June 1999. Rates for systemic hypersensitivity reactions were 0.8 and 6.3 per 100,000 doses in Japan and the United States, respectively. Passively collected VAERS surveillance data indicate that characteristic hypersensitivity reactions with a delayed onset continue to occur among JEV recipients and that conservative recommendations limiting its use to travelers at high risk of infection with Japanese encephalitis are appropriate.

  16. Pre-cut Filter Paper for Detecting Anti-Japanese Encephalitis Virus IgM from Dried Cerebrospinal Fluid Spots

    PubMed Central

    Bharucha, Tehmina; Chanthongthip, Anisone; Phuangpanom, Soumphou; Phonemixay, Ooyanong; Sengvilaipaseuth, Onanong; Vongsouvath, Manivanh; Lee, Sue; Newton, Paul N.; Dubot-Pérès, Audrey

    2016-01-01

    Background The use of filter paper as a simple, inexpensive tool for storage and transportation of blood, ‘Dried Blood Spots’ or Guthrie cards, for diagnostic assays is well-established. In contrast, there are a paucity of diagnostic evaluations of dried cerebrospinal fluid (CSF) spots. These have potential applications in low-resource settings, such as Laos, where laboratory facilities for central nervous system (CNS) diagnostics are only available in Vientiane. In Laos, a major cause of CNS infection is Japanese encephalitis virus (JEV). We aimed to develop a dried CSF spot protocol and to evaluate its diagnostic performance using the World Health Organisation recommended anti-JEV IgM antibody capture enzyme-linked immunosorbent assay (JEV MAC-ELISA). Methodology and Principal Findings Sample volumes, spotting techniques and filter paper type were evaluated using a CSF-substitute of anti-JEV IgM positive serum diluted in Phosphate Buffer Solution (PBS) to end-limits of detection by JEV MAC-ELISA. A conventional protocol, involving eluting one paper punch in 200μl PBS, did not detect the end-dilution, nor did multiple punches utilising diverse spotting techniques. However, pre-cut filter paper enabled saturation with five times the volume of CSF-substitute, sufficiently improving sensitivity to detect the end-dilution. The diagnostic accuracy of this optimised protocol was compared with routine, neat CSF in a pilot, retrospective study of JEV MAC-ELISA on consecutive CSF samples, collected 2009–15, from three Lao hospitals. In comparison to neat CSF, 132 CSF samples stored as dried CSF spots for one month at 25–30°C showed 81.6% (65.7–92.3 95%CI) positive agreement, 96.8% (91.0–99.3 95%CI) negative agreement, with a kappa coefficient of 0.81 (0.70–0.92 95%CI). Conclusions/Significance The novel design of pre-cut filter paper saturated with CSF could provide a useful tool for JEV diagnostics in settings with limited laboratory access. It has the

  17. Study on persistent infection of Japanese encephalitis virus Beijing-1 strain in serum-free Sf9 cell cultures.

    PubMed

    Kim, Hun; Lee, Su Jeen; Park, Jin Yong; Park, Yong Wook; Kim, Hyun Sung; Kang, Heui-Yun; Hur, Byung-Ki; Ryu, Yeon-Woo; Han, Sang In; Kim, Jong Su

    2004-03-01

    Sf9 cells have obvious advantages for the conventional production technology of vaccine. They are useful tools for high concentration and large-scale cultures. Sf9 cells were grown to maximal concentration, 8 x 10(6) cells/ml in a 500ml spinner flask, with a doubling time at the exponentially growing phase of 24.5 hours, using serum-free media. To explore the ability of Sf9 cells to be infected by the Japanese encephalitis (JE) virus Beijing-1 strain, Sf9 cells were infected with the virus. By 4-5 days post-infection, 10-15% of the Sf9 cells showed cytopathic effect (CPE), from granularity to the formation of syncytia and multinucleated giant cells continuously observed over a period of 35 days. Positive fluorescent reactions were detected in 30-40% of cells infected with the JE virus Beijing-1 strain, and the uninfected Sf9 cells were completely negative. Virus particles, propagated in Sf9 and Vero cells, were concentrated by sedimentation on 40% trehalose cushions by ultracentrifugation, and showed identical patterns of viral morphogenesis. Complete virus particles, 40 to 50 nm in diameter, were observed, and JE virus envelope (E) proteins, at 53 kDa, were found in the western blot analysis to the anti-JE virus E protein monoclonal antibody and reacted as a magenta band in the same position to the glycoprotein staining. To evaluate whether the infectious virus was produced in Sf9 cells inoculated with the JE virus Beijing-1 stain, Sf9 cells were inoculated with the virus, and sample harvested every 5 days. The titers of the JE virus Beijing-1 strain rose from 1.0 x 10(5) to 1.5 x 10(6) pfu/ml. The infected Sf9 cells could be sub-cultured in serum-free medium, with no change in the plaque sizes formed by the JE virus Beijing-1 strain in the plaque assay. It is suggested that the ability of the JE virus Beijing-1 strain to infect Sf9 cells in serum-free media will provide a useful insect cell system, where the JE virus replication, cytopathogenicity and vaccine

  18. Nitric oxide and virus infection

    PubMed Central

    Akaike, T; Maeda, H

    2000-01-01

    Nitric oxide (NO) has complex and diverse functions in physiological and pathophysiological phenomena. The mechanisms of many events induced by NO are now well defined, so that a fundamental understanding of NO biology is almost established. Accumulated evidence suggests that NO and oxygen radicals such as superoxide are key molecules in the pathogenesis of various infectious diseases. NO biosynthesis, particularly through expression of an inducible NO synthase (iNOS), occurs in a variety of microbial infections. Although antimicrobial activity of NO is appreciated for bacteria and protozoa, NO has opposing effects in virus infections such as influenza virus pneumonia and certain other neurotropic virus infections. iNOS produces an excessive amount of NO for long periods, which allows generation of a highly reactive nitrogen oxide species, peroxynitrite, via a radical coupling reaction of NO with superoxide. Thus, peroxynitrite causes oxidative tissue injury through potent oxidation and nitration reactions of various biomolecules. NO also appears to affect a host's immune response, with immunopathological consequences. For example, overproduction of NO in virus infections in mice is reported to suppress type 1 helper T-cell-dependent immune responses, leading to type 2 helper T-cell-biased immunological host responses. Thus, NO may be a host response modulator rather than a simple antiviral agent. The unique biological properties of NO are further illustrated by our recent data suggesting that viral mutation and evolution may be accelerated by NO-induced oxidative stress. Here, we discuss these multiple roles of NO in pathogenesis of virus infections as related to both non-specific inflammatory responses and immunological host reactions modulated by NO during infections in vivo. PMID:11106932

  19. Travelers' Health: Japanese Encephalitis

    MedlinePlus

    ... species. The virus is maintained in an enzootic cycle between mosquitoes and amplifying vertebrate hosts, primarily pigs ... still maintained in these areas in an enzootic cycle between animals and mosquitoes. Therefore, susceptible visitors may ...

  20. 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.

  1. WHO working group on the quality, safety and efficacy of japanese encephalitis vaccines (live attenuated) for human use, Bangkok, Thailand, 21-23 February 2012.

    PubMed

    Trent, Dennis W; Minor, Philip; Jivapaisarnpong, Teeranart; Shin, Jinho

    2013-11-01

    Japanese encephalitis (JE) is one of the most important viral encephalitides in Asia. Two live-attenuated vaccines have been developed and licensed for use in countries in the region. Given the advancement of immunization of humans with increasing use of live-attenuated vaccines to prevent JE, there is increased interest to define quality standards for their manufacture, testing, nonclinical studies, and clinical studies to assess their efficacy and safety in humans. To this end, WHO convened a meeting with a group of international experts in February 2012 to develop guidelines for evaluating the quality, safety and efficacy of live-attenuated JE virus vaccines for prevention of human disease. This report summarizes collective views of the participants on scientific and technical issues that need to be considered in the guidelines.

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

    PubMed

    Upadhyay, Anup K; Cyr, Matthew; Longenecker, Kenton; Tripathi, Rakesh; Sun, Chaohong; Kempf, Dale J

    2017-03-01

    The rapid spread of the recent Zika 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 of Zika 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 group P21212 and containing two protein molecules in the asymmetric unit. The structure is similar to that reported for the NS5 protein from Japanese encephalitis virus and suggests opportunities for structure-based drug design targeting either its MTase or RdRp domain.

  3. Epidemiological processes involved in the emergence of vector-borne diseases: West Nile fever, Rift Valley fever, Japanese encephalitis and Crimean-Congo haemorrhagic fever.

    PubMed

    Chevalier, V; de la Rocque, S; Baldet, T; Vial, L; Roger, F

    2004-08-01

    Over the past few decades, the geographical distribution of arthropod-borne zoonoses has dramatically expanded. The influence of human-induced or ecological changes on the risk of disease outbreaks is undeniable. However, few hypotheses have been proposed which address the re-emergence of these diseases, the spread of these viruses to previously uninfected areas and their establishment therein. Host and vector movements play an important role in the dissemination of pathogens, and the ability of these diseases to colonise previously uninfected areas may be explained by the diversity of hosts and vectors, the presence of favourable ecological conditions, and the successful adaptations of vectors or pathogens to new ecosystems. The objective of this paper is to describe the epidemiological processes of the vector-borne diseases Rift Valley fever, West Nile fever, Japanese encephalitis and Crimean-Congo haemorrhagic fever.

  4. Development of a small animal peripheral challenge model of Japanese encephalitis virus using interferon deficient AG129 mice and the SA14-14-2 vaccine virus strain.

    PubMed

    Calvert, Amanda E; Dixon, Kandice L; Delorey, Mark J; Blair, Carol D; Roehrig, John T

    2014-01-03

    Japanese encephalitis virus (JEV) is the most common cause of viral encephalitis in Asia, and it is increasingly a global public health concern due to its recent geographic expansion. While commercial vaccines are available and used in some endemic countries, JEV continues to be a public health problem, with 50,000 cases reported annually. Research with virulent JEV in mouse models to develop new methods of prevention and treatment is restricted to BSL-3 containment facilities, confining these studies to investigators with access to these facilities. We have developed an adult small animal peripheral challenge model using interferon-deficient AG129 mice and the JEV live-attenuated vaccine SA14-14-2, thus requiring only BSL-2 containment. A low dose of virus (10PFU/0.1ml) induced 100% morbidity in infected mice. Increased body temperatures measured by implantable temperature transponders correlated with an increase in infectious virus and viral RNA in serum, spleen and brain as well as an increase in pro-inflammatory markers measured by a 58-biomarker multi-analyte profile (MAP) constructed during the course of infection. In the future, the MAP measurements can be used as a baseline for comparison in order to better assess the inhibition of disease progression by other prophylactic and therapeutic agents. The use of the AG129/JEV SA14-14-2 animal model makes vaccine and therapeutic studies feasible for laboratories with limited biocontainment facilities.

  5. Alleviative Effects of a Kampo (a Japanese Herbal) Medicine “Maoto (Ma-Huang-Tang)” on the Early Phase of Influenza Virus Infection and Its Possible Mode of Action

    PubMed Central

    Kataoka, Erika; Aoki, Yuka; Hokari, Rei

    2014-01-01

    A Kampo medicine, maoto, has been prescribed in an early phase of influenza-like illness and used for a treatment of influenza clinically in Japan these days. However, the efficacy of maoto against the virus infection remains to be elucidated. This study was conducted to evaluate the alleviative effects of maoto against early phase of influenza virus infection and its preliminary mode of actions through immune systems. When maoto (0.9 and 1.6 g/kg/day) was orally administered to A/J mice on upper respiratory tract infection of influenza virus A/PR/8/34 from 4 hours to 52 hours postinfection (p.i.) significant antipyretic effect was shown in comparison with water-treated control. Administration of maoto (0.8 and 1.3 g/kg/day) significantly decreased the virus titers in both nasal (NLF) and bronchoalveolar lavage fluids (BALF) at 52 hours p.i., and significantly increased the anti-influenza virus IgM, IgA, and IgG1 antibody titers in NLF, BALF, and serum, respectively. Maoto also increased significantly the influenza virus-bound IgG1 and IgM antibody titers in serum and the virus-bound IgM antibody titer in even the BALF of uninfected A/J mice. These results indicate that maoto exerts antipyretic activity in influenza virus-infected mice and virus reducing effect at an early phase of the infection through probably augmentation of the virus-bound natural antibodies. PMID:24778699

  6. Eco-friendly larvicides from Indian plants: Effectiveness of lavandulyl acetate and bicyclogermacrene on malaria, dengue and Japanese encephalitis mosquito vectors.

    PubMed

    Govindarajan, Marimuthu; Benelli, Giovanni

    2016-11-01

    Mosquitoes (Diptera: Culicidae) are a key threat for millions of people and animals worldwide, since they act as vectors for devastating pathogens and parasites, including malaria, dengue, Japanese encephalitis, filiariasis and Zika virus. Mosquito young instars are usually targeted using organophosphates, insect growth regulators and microbial agents. Indoor residual spraying and insecticide-treated bed nets are also employed. However, these chemicals have negative effects on human health and the environment and induce resistance in a number of vectors. In this scenario, newer and safer tools have been recently implemented to enhance mosquito control. The concrete potential of screening plant species as sources of metabolites for entomological and parasitological purposes is worthy of attention, as recently elucidated by the Y. Tu's example. Here we investigated the toxicity of Heracleum sprengelianum (Apiaceae) leaf essential oil and its major compounds toward third instar larvae of the malaria vector Anopheles subpictus, the arbovirus vector Aedes albopictus and the Japanese encephalitis vector Culex tritaeniorhynchus. GC-MS analysis showed that EO major components were lavandulyl acetate (17.8%) and bicyclogermacrene (12.9%). The EO was toxic to A. subpictus, A. albopictus, and C. tritaeniorhynchus, with LC50 of 33.4, 37.5 and 40.9µg/ml, respectively. Lavandulyl acetate was more toxic to mosquito larvae if compared to bicyclogermacrene. Their LC50 were 4.17 and 10.3µg/ml for A. subpictus, 4.60 and 11.1µg/ml for A. albopictus, 5.11 and 12.5µg/ml for C. tritaeniorhynchus. Notably, the EO and its major compounds were safer to three non-target mosquito predators, Anisops bouvieri, Diplonychus indicus and Gambusia affinis, with LC50 ranging from 206 to 4219µg/ml. Overall, this study highlights that H. sprengelianum EO is a promising source of eco-friendly larvicides against three important mosquito vectors with moderate toxicity against non-target aquatic

  7. Role of Natural Killer Cells in Innate Protection Against Lethal Ebola Virus Infection

    DTIC Science & Technology

    2007-11-02

    Cells Protect against Lethal Ebola Virus Infection174 Several viruses , including human cytomegalovirus, HIV, and Epstein-Barr virus replicate...with VRP-encoding Ebola VP40 blocked IFN- se- cretion induced by the VLPs, whereas control sera from mice vaccinated with a VRP encoding the Lassa virus ...encephalitis replicon particles expressing VP40 (VRP-VP40), or Lassa virus N (VRP- Lassa ), were preincubated for 1 h on ice with 10 g of VLPs

  8. [Zika virus infection during pregnancy].

    PubMed

    Picone, O; Vauloup-Fellous, C; D'Ortenzio, E; Huissoud, C; Carles, G; Benachi, A; Faye, A; Luton, D; Paty, M-C; Ayoubi, J-M; Yazdanpanah, Y; Mandelbrot, L; Matheron, S

    2016-05-01

    A Zika virus epidemic is currently ongoing in the Americas. This virus is linked to congenital infections with potential severe neurodevelopmental dysfunction. However, incidence of fetal infection and whether this virus is responsible of other fetal complications are still unknown. National and international public health authorities recommend caution and several prevention measures. Declaration of Zika virus infection is now mandatory in France. Given the available knowledge on Zika virus, we suggest here a review of the current recommendations for management of pregnancy in case of suspicious or infection by Zika virus in a pregnant woman.

  9. Primary antibody responses of herons to experimental infection with Murray Valley encephalitis and Kunjin viruses.

    PubMed

    Boyle, D B; Marshall, I D; Dickerman, R W

    1983-12-01

    Antibody responses of rufous night herons (Nycticorax caledonicus) and little egrets (Egretta garzetta) following infection with Murray Valley encephalitis and Kunjin viruses were determined. Haemagglutinin-inhibiting antibodies were first detected on day 5 or 6 after inoculation and increased rapidly, reaching maximum titres of 320 to 2560 between 10 and 20 days after inoculation. Titres declined 20-320 between 60 and 120 days after inoculation, then tended to remain stationary. Titres were 2- to 8-fold higher to infecting virus than heterologous virus. Neutralizing antibody development paralleled that of HI antibodies with titres maintained at a higher level for longer periods; however, they did eventually decline to low levels. Following MVE virus infection IgM (19S), HI antibodies were 80-100% of HI antibodies detectable on day 6 or 7 after inoculation and declined rapidly, becoming undetectable by 20 days after inoculation. With Kunjin virus infections, IgM HI antibodies represented 90-100% of HI antibodies detectable on day 6 or 7 after inoculation. Significant levels of IgM HI antibodies were still detectable 20 days after inoculation (5-30% of total HI antibodies) and, in some birds, even at 27 days after inoculation (up to 10%), IgG (7S) HI antibodies were low or undetectable on day 6 or 7 after inoculation, then increased rapidly with rapidly rising HI antibody titres. The specificity of IgM and IgG antibodies and unfractionated sera was determined by testing against Murray Valley encephalitis, Kunjin, Japanese encephalitis and West Nile virus haemagglutinating antigens. It was possible to determine with which virus a bird had been infected from the pattern of cross-reaction with these antigens. These results should provide a rational basis for the interpretation of serological results from naturally infected birds.

  10. Anti Japanese encephalitis virus IgM positivity among patients with acute encephalitic syndrome admitted to different hospitals from all over Nepal

    PubMed Central

    Bhattarai, Anupama; Nepal, Krishus; Adhikari, Sailaja; Sharma, Mukunda; Parajuli, Pramila

    2017-01-01

    The Japanese encephalitis virus (JEV) infection is one of the major public health problems in Nepal because of its increasing disease morbidity and mortality. The main purpose of this study was to determine the anti-JEV IgM positivity among acute encephalitis syndromic cases from all over Nepal. The present study was conducted at National Public Health Laboratory, Kathmandu, Nepal from April 2015 to October 2015. A total of 671 (418 CSF and 253 serum) samples were collected from 625 patients with acute encephalitic syndrome, admitted to different hospitals from all over Nepal. IgM antibody capture enzyme linked immunosorbent assay (ELISA) was used for the detection of anti-JEV IgM positive cases. The rate of anti-JEV IgM positivity was found to be 21.12%. The majority of positive cases (50%) were from the age group below 15 years, with the highest numbers of cases occurring in September (55.30%). Among all the anti-JEV IgM positive cases, higher numbers of cases were males. Geographically, the highest numbers of anti-JEV IgM positive cases were recorded from Terai region. Similarly, largest numbers of anti-JEV IgM positive cases were reported from Kailai district followed by those from Kanchanpur. However, anti-JEV IgM positive cases were also reported from hill districts. Continuation of active surveillance and vector control measures, proper management of diagnostic facilities and expanded program of immunization in JE endemic areas should be strongly emphasized to reduce the endemicity of the disease. PMID:28264024

  11. Anti Japanese encephalitis virus IgM positivity among patients with acute encephalitic syndrome admitted to different hospitals from all over Nepal.

    PubMed

    Bhattarai, Anupama; Pant, Narayan Dutt; Nepal, Krishus; Adhikari, Sailaja; Sharma, Mukunda; Parajuli, Pramila

    2017-01-01

    The Japanese encephalitis virus (JEV) infection is one of the major public health problems in Nepal because of its increasing disease morbidity and mortality. The main purpose of this study was to determine the anti-JEV IgM positivity among acute encephalitis syndromic cases from all over Nepal. The present study was conducted at National Public Health Laboratory, Kathmandu, Nepal from April 2015 to October 2015. A total of 671 (418 CSF and 253 serum) samples were collected from 625 patients with acute encephalitic syndrome, admitted to different hospitals from all over Nepal. IgM antibody capture enzyme linked immunosorbent assay (ELISA) was used for the detection of anti-JEV IgM positive cases. The rate of anti-JEV IgM positivity was found to be 21.12%. The majority of positive cases (50%) were from the age group below 15 years, with the highest numbers of cases occurring in September (55.30%). Among all the anti-JEV IgM positive cases, higher numbers of cases were males. Geographically, the highest numbers of anti-JEV IgM positive cases were recorded from Terai region. Similarly, largest numbers of anti-JEV IgM positive cases were reported from Kailai district followed by those from Kanchanpur. However, anti-JEV IgM positive cases were also reported from hill districts. Continuation of active surveillance and vector control measures, proper management of diagnostic facilities and expanded program of immunization in JE endemic areas should be strongly emphasized to reduce the endemicity of the disease.

  12. Probiotics in respiratory virus infections.

    PubMed

    Lehtoranta, L; Pitkäranta, A; Korpela, R

    2014-08-01

    Viral respiratory infections are the most common diseases in humans. A large range of etiologic agents challenge the development of efficient therapies. Research suggests that probiotics are able to decrease the risk or duration of respiratory infection symptoms. However, the antiviral mechanisms of probiotics are unclear. The purpose of this paper is to review the current knowledge on the effects of probiotics on respiratory virus infections and to provide insights on the possible antiviral mechanisms of probiotics. A PubMed and Scopus database search was performed up to January 2014 using appropriate search terms on probiotic and respiratory virus infections in cell models, in animal models, and in humans, and reviewed for their relevance. Altogether, thirty-three clinical trials were reviewed. The studies varied highly in study design, outcome measures, probiotics, dose, and matrices used. Twenty-eight trials reported that probiotics had beneficial effects in the outcome of respiratory tract infections (RTIs) and five showed no clear benefit. Only eight studies reported investigating viral etiology from the respiratory tract, and one of these reported a significant decrease in viral load. Based on experimental studies, probiotics may exert antiviral effects directly in probiotic-virus interaction or via stimulation of the immune system. Although probiotics seem to be beneficial in respiratory illnesses, the role of probiotics on specific viruses has not been investigated sufficiently. Due to the lack of confirmatory studies and varied data available, more randomized, double-blind, and placebo-controlled trials in different age populations investigating probiotic dose response, comparing probiotic strains/genera, and elucidating the antiviral effect mechanisms are necessary.

  13. Comparison of the immunogenicity and safety of measles vaccine administered alone or with live, attenuated Japanese encephalitis SA 14-14-2 vaccine in Philippine infants.

    PubMed

    Gatchalian, Salvacion; Yao, Yafu; Zhou, Benli; Zhang, Lei; Yoksan, Sutee; Kelly, Kim; Neuzil, Kathleen M; Yaïch, Mansour; Jacobson, Julie

    2008-04-24

    Japanese encephalitis (JE) virus is a major cause of disease, disability, and death in Asia. An effective, live, attenuated JE vaccine (LJEV) is available; however, its use in routine immunization schedules is hampered by lack of data on concomitant administration with measles vaccine (MV). This study evaluated the immunogenicity and reactogenicity of LJEV and MV when administered at the same or separate study visits in infants younger than 1 year of age. Three groups of healthy infants were randomized to receive LJEV at age of 8 months and MV at 9 months (Group 1; n=100); MV and LJEV together at 9 months (Group 2; n=236); or MV and LJEV at 9 and 10 months, respectively (Group 3; n=235). Blood was obtained 4 weeks after each vaccine administration to determine antibody levels for measles and JE. Reactogenicity was assessed by parental diaries and clinic visits. Four weeks after immunization, measles seroprotection rates (defined as > or =340 mIU/ml) were high and comparable in all three groups and specifically, rates in the combined MV-LJEV (Group 2) were not statistically inferior to those in Group 3 receiving MV separately (96% versus 100%, respectively). Likewise, the LJEV seroprotection rates were high and similar between the three groups. The reactogenicity profiles of the three vaccine schedules were also analogous. LJEV and MV administered together are well tolerated and immunogenic in infants younger than 1 year. These results should facilitate incorporation of LJEV into routine immunization schedules with MV.

  14. Toxicity of saponin isolated from Gymnema sylvestre R. Br. (Asclepiadaceae) against Culex tritaeniorhynchus Giles (Diptera: Culicidae) Japanese encephalitis vector mosquito in India.

    PubMed

    Elumalai, Kupppusamy; Dhanasekaran, Shanmugan; Krishnappa, Kaliamoorthy

    2012-12-01

    To determine the larvicidal activity of various extracts of Gymnema sylvestre against the Japanese Encephalitis vector, Culex tritaeniorynchus in Tamilnadu, India. To identify the active principle present in the promising fraction obtained in Chlorofom:Methanol extract of Fraction 2. The G. sylvestre leaf extracts were tested, employing WHO procedure against fourth instar larvae of C. tritaeniorhynchus and the larval mortalities were recorded at various concentrations (6.25, 12.5, 25.0, 50 and 100 µg/mL); the 24h LC50 values of the G. Sylvestre leaf extracts were determined following Probit analysis. It was noteworthy that treatment level 100 µg/mL exhibited highest mortality rates for the three different crude extracts and was significantly different from the mean mortalities recorded for the other concentrations. The LC50 values of 34.756 µg/mL (24.475-51.41), 31.351 µg/mL (20.634-47.043) and 28.577 µg/mL (25.159-32.308) were calculated for acetone, chloroform and methanol extract with the chi-square values of 10.301, 31.351 and 4.093 respectively. The present investigation proved that G. Sylvestre could be possibly utilized as an important component in the Vector Control Program.

  15. Field trial of Bacillus sphaericus strain B-101 (serotype H5a, 5b) against filariasis and Japanese encephalitis vectors in India.

    PubMed

    Yadav, R S; Sharma, V P; Upadhyay, A K

    1997-06-01

    A large-scale operational field trial was conducted from June 1993 to October 1994 to evaluate the efficacy of Bacillus sphaericus (strain B-101, serotype H5a,5b) for control of the vectors of filariasis (Culex quinquefasciatus) and Japanese encephalitis (Cx. tritaeniorhynchus and Cx. vishnui) in Rourkela city. Application of B. sphaericus, when sprayed at 1 g/m2 in storm drains, wastewater pools, abandoned masonry tanks, peripheral paddy fields, ditches, and other small water collections and at 4 g/m2 in domestic septic tanks, significantly reduced larval and pupal counts (P < 0.0001) and significantly reduced the percentage of habitats containing larvae (3rd-4th instars) (P < 0.0001) as compared with routine antilarval measures. This in turn resulted in a reduction in the indoor density of disease vectors in particular and a reduction in mosquito nuisance in general. The trial demonstrated that B. sphaericus has good potential for use against disease vectors and mosquito breeding in polluted as well as clean waters.

  16. 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.

  17. Spatial and Temporal Variation of Japanese encephalitis Disease and Detection of Disease Hotspots: a Case Study of Gorakhpur District, Uttar Pradesh, India

    NASA Astrophysics Data System (ADS)

    Verma, S.; Gupta, R. D.

    2014-11-01

    In recent times, Japanese Encephalitis (JE) has emerged as a serious public health problem. In India, JE outbreaks were recently reported in Uttar Pradesh, Gorakhpur. The present study presents an approach to use GIS for analyzing the reported cases of JE in the Gorakhpur district based on spatial analysis to bring out the spatial and temporal dynamics of the JE epidemic. The study investigates spatiotemporal pattern of the occurrence of disease and detection of the JE hotspot. Spatial patterns of the JE disease can provide an understanding of geographical changes. Geospatial distribution of the JE disease outbreak is being investigated since 2005 in this study. The JE incidence data for the years 2005 to 2010 is used. The data is then geo-coded at block level. Spatial analysis is used to evaluate autocorrelation in JE distribution and to test the cases that are clustered or dispersed in space. The Inverse Distance Weighting interpolation technique is used to predict the pattern of JE incidence distribution prevalent across the study area. Moran's I Index (Moran's I) statistics is used to evaluate autocorrelation in spatial distribution. The Getis-Ord Gi*(d) is used to identify the disease areas. The results represent spatial disease patterns from 2005 to 2010, depicting spatially clustered patterns with significant differences between the blocks. It is observed that the blocks on the built up areas reported higher incidences.

  18. Induction of protective immunity in animals vaccinated with recombinant vaccinia viruses that express PreM and E glycoproteins of Japanese encephalitis virus.

    PubMed Central

    Yasuda, A; Kimura-Kuroda, J; Ogimoto, M; Miyamoto, M; Sata, T; Sato, T; Takamura, C; Kurata, T; Kojima, A; Yasui, K

    1990-01-01

    A cDNA clone representing the genome of structural proteins of Japanese encephalitis virus (JEV) was inserted into the thymidine kinase gene of vaccinia virus strains LC16mO and WR under the control of a strong early-late promoter for the vaccinia virus 7.5-kilodalton polypeptide. Indirect immunofluorescence and fluorescence-activated flow cytometric analysis revealed that the recombinant vaccinia viruses expressed JEV E protein on the membrane surface, as well as in the cytoplasm, of recombinant-infected cells. In addition, the E protein expressed from the JEV recombinants reacted to nine different characteristic monoclonal antibodies, some of which have hemagglutination-inhibiting and JEV-neutralizing activities. Radioimmunoprecipitation analysis demonstrated that two major proteins expressed in recombinant-infected cells were processed and glycosylated as the authentic PreM and E glycoproteins of JEV. Inoculation of rabbits with the infectious recombinant vaccinia virus resulted in rapid production of antiserum specific for the PreM and E glycoproteins of JEV. This antiserum had both hemagglutination-inhibiting and virus-neutralizing activities against JEV. Furthermore, mice vaccinated with the recombinant also produced JEV-neutralizing antibodies and were resistant to challenge with JEV. Images PMID:2159544

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

    PubMed Central

    Upadhyay, Anup K.; Longenecker, Kenton; Tripathi, Rakesh; Sun, Chaohong; Kempf, Dale J.

    2017-01-01

    The rapid spread of the recent Zika 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 of Zika 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 group P21212 and containing two protein molecules in the asymmetric unit. The structure is similar to that reported for the NS5 protein from Japanese encephalitis virus and suggests opportunities for structure-based drug design targeting either its MTase or RdRp domain. PMID:28291746

  20. Construction and preliminary investigation of a novel dengue serotype 4 chimeric virus using Japanese encephalitis vaccine strain SA14-14-2 as the backbone.

    PubMed

    Li, Zhushi; Yang, Huiqiang; Yang, Jian; Lin, Hua; Wang, Wei; Liu, Lina; Zhao, Yu; Liu, Li; Zeng, Xianwu; Yu, Yongxin; Li, Yuhua

    2014-10-13

    For the purpose of developing a novel dengue vaccine candidate, recombinant plasmids were constructed which contained the full length cDNA clone of Japanese encephalitis (JE) vaccine strain SA14-14-2 with its premembrane (PreM) and envelope (E) genes replaced by the counterparts of dengue virus type 4 (DENV4). By transfecting the in vitro transcription products of the recombinant plasmids into BHK-21 cells, a chimeric virus JEV/DENV4 was successfully recovered. The chimeric virus was identified by complete genome sequencing, Western blot and immunofluorescent staining. Growth characteristics revealed it was well adapted to primary hamster kidney (PHK) cells. Its genetic stability was investigated and only one unintentional mutation in 5'-untranslated region (5'-UTR) was found after 20 passages in PHK cells. Neurotropism, neurovirulence and immunogenicity of the chimeric virus were tested in mice. Besides, the influence of JE vaccine pre-immunization on the neutralizing antibody level induced by the chimeric virus was illuminated. To our knowledge, this is the first chimeric virus incorporating the JE vaccine stain SA14-14-2 and DENV4. It is probably a potential candidate to compose a tetravalent dengue chimeric vaccine.

  1. A novel dengue virus serotype 1 vaccine candidate based on Japanese encephalitis virus vaccine strain SA14-14-2 as the backbone.

    PubMed

    Yang, Huiqiang; Li, Zhushi; Lin, Hua; Wang, Wei; Yang, Jian; Liu, Lina; Zeng, Xianwu; Wu, Yonglin; Yu, Yongxin; Li, Yuhua

    2016-06-01

    To develop a potential dengue vaccine candidate, a full-length cDNA clone of a novel chimeric virus was constructed using recombinant DNA technology, with Japanese encephalitis virus (JEV) vaccine strain SA14-14-2 as the backbone, with its premembrane (prM) and envelope (E) genes substituted by their counterparts from dengue virus type 1 (DENV1). The chimeric virus (JEV/DENV1) was successfully recovered from primary hamster kidney (PHK) cells by transfection with the in vitro transcription products of JEV/DENV1 cDNA and was identified by complete genome sequencing and immunofluorescent staining. No neuroinvasiveness of this chimeric virus was observed in mice inoculated by the subcutaneous route (s.c.) or by the intraperitoneal route (i.p.), while some neurovirulence was displayed in mice that were inoculated directly by the intracerebral route (i.c.). The chimeric virus was able to stimulate high-titer production of antibodies against DENV1 and provided protection against lethal challenge with neuroadapted dengue virus in mice. These results suggest that the chimeric virus is a promising dengue vaccine candidate.

  2. Reemergence of St. Louis Encephalitis Virus, California, 2015

    PubMed Central

    White, Gregory S.; Symmes, Kelly; Sun, Pu; Fang, Ying; Garcia, Sandra; Steiner, Cody; Smith, Kirk; Reisen, William K.

    2016-01-01

    St. Louis encephalitis virus infection was detected in summer 2015 in southern California after an 11-year absence, concomitant with an Arizona outbreak. Sequence comparisons showed close identity of California and Arizona isolates with 2005 Argentine isolates, suggesting introduction from South America and underscoring the value of continued arbovirus surveillance. PMID:27869600

  3. Japanese Encephalitis Virus NS5 Inhibits the Type I Interferon Production by Blocking the Nuclear Translocation of IRF3 and NF-κB.

    PubMed

    Ye, Jing; Chen, Zheng; Li, Yunchuan; Zhao, Zikai; He, Wen; Zohaib, Ali; Song, Yunfeng; Deng, Chenglin; Zhang, Bo; Chen, Huanchun; Cao, Shengbo

    2017-02-08

    The type I interferon (IFN) response is part of a first-line defense against viral infection. To initiate replication, viruses have developed powerful evasion strategies to counteract host IFN responses. In present study, we found that Japanese encephalitis virus (JEV) NS5 protein could inhibit double strand RNA (dsRNA)-induced IFN-β expression in a dose-dependent manner. Our data further demonstrated that JEV NS5 suppressed the activation of IFN transcriptional factors, IRF3 and NF-κB. However, there was no defect in the phosphorylation of IRF3 and degradation of IκB, an upstream inhibitor of NF-κB, upon NS5 expression, indicating a direct inhibition of the nuclear localization of IRF3 and NF-κB by NS5. Mechanically, NS5 was shown to interact with the nuclear transport proteins, KPNA2, KPNA3 and KPNA4, which competitively blocked the interaction of KPNA3 and KPNA4 with their cargo molecules, IRF3 and p65, a subunit of NF-κB, and thus inhibited the nuclear translocation of IRF3 and NF-κB. Furthermore, overexpression of KPNA3 and KPNA4 restored the activity of IRF3 and NF-κB and increased the production of IFN-β in NS5-expressing or JEV-infected cells. Additionally, an up-regulated replication level of JEV was shown upon KPNA3 or KPNA4 overexpression. These results suggest that JEV NS5 inhibits the induction of type I IFN by targeting KPNA3 and KPNA4.IMPORTANCE JEV is the major cause of viral encephalitis in South and Southeast Asia with high mortality. However, the molecular mechanisms contributing to the severe pathogenesis are poorly understood. The ability of JEV to counteract the host innate immune response may be one of the potential mechanisms responsible for JEV virulence. Here, we demonstrate the ability of JEV NS5 to interfere with the dsRNA-induced nuclear translocation of IRF3 and NF-κB by competitively inhibiting the interaction of IRF3 and NF-κB with nuclear transport proteins. Via this mechanism, JEV NS5 suppresses the induction of type I

  4. Cellular Immune Responses to Live Attenuated Japanese Encephalitis (JE) Vaccine SA14-14-2 in Adults in a JE/Dengue Co-Endemic Area

    PubMed Central

    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

    Background 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. Methods 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. Results 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. Conclusions 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. Trial Registration clinicaltrials.gov (NCT01656200) PMID:28135273

  5. Formalin Inactivation of Japanese Encephalitis Virus Vaccine Alters the Antigenicity and Immunogenicity of a Neutralization Epitope in Envelope Protein Domain III

    PubMed Central

    Fan, Yi-Chin; Chiu, Hsien-Chung; Chen, Li-Kuang; Chang, Gwong-Jen J.; Chiou, Shyan-Song

    2015-01-01

    Formalin-inactivated Japanese encephalitis virus (JEV) vaccines are widely available, but the effects of formalin inactivation on the antigenic structure of JEV and the profile of antibodies elicited after vaccination are not well understood. We used a panel of monoclonal antibodies (MAbs) to map the antigenic structure of live JEV virus, untreated control virus (UCV), formalin-inactivated commercial vaccine (FICV), and formalin-inactivated virus (FIV). The binding activity of T16 MAb against Nakayama-derived FICV and several strains of FIV was significantly lower compared to live virus and UCV. T16 MAb, a weakly neutralizing JEV serocomplex antibody, was found to inhibit JEV infection at the post-attachment step. The T16 epitope was mapped to amino acids 329, 331, and 389 within domain III (EDIII) of the envelope (E) glycoprotein. When we explored the effect of formalin inactivation on the immunogenicity of JEV, we found that Nakayama-derived FICV, FIV, and UCV all exhibited similar immunogenicity in a mouse model, inducing anti-JEV and anti-EDII 101/106/107 epitope-specific antibodies. However, the EDIII 329/331/389 epitope-specific IgG antibody and neutralizing antibody titers were significantly lower for FICV-immunized and FIV-immunized mouse serum than for UCV-immunized. Formalin inactivation seems to alter the antigenic structure of the E protein, which may reduce the potency of commercially available JEV vaccines. Virus inactivation by H2O2, but not by UV or by short-duration and higher temperature formalin treatment, is able to maintain the antigenic structure of the JEV E protein. Thus, an alternative inactivation method, such as H2O2, which is able to maintain the integrity of the E protein may be essential to improving the potency of inactivated JEV vaccines. PMID:26495991

  6. Envelope Protein Mutations L107F and E138K Are Important for Neurovirulence Attenuation for Japanese Encephalitis Virus SA14-14-2 Strain

    PubMed Central

    Yang, Jian; Yang, Huiqiang; Li, Zhushi; Wang, Wei; Lin, Hua; Liu, Lina; Ni, Qianzhi; Liu, Xinyu; Zeng, Xianwu; Wu, Yonglin; Li, Yuhua

    2017-01-01

    The attenuated Japanese encephalitis virus (JEV) strain SA14-14-2 has been successfully utilized to prevent JEV infection; however, the attenuation determinants have not been fully elucidated. The envelope (E) protein of the attenuated JEV SA14-14-2 strain differs from that of the virulent parental SA14 strain at eight amino acid positions (E107, E138, E176, E177, E264, E279, E315, and E439). Here, we investigated the SA14-14-2-attenuation determinants by mutating E107, E138, E176, E177, and E279 in SA14-14-2 to their status in the parental virulent strain and tested the replication capacity, neurovirulence, neuroinvasiveness, and mortality associated with the mutated viruses in mice, as compared with those of JEV SA14-14-2 and SA14. Our findings indicated that revertant mutations at the E138 or E107 position significantly increased SA14-14-2 virulence, whereas other revertant mutations exhibited significant increases in neurovirulence only when combined with E138, E107, and other mutations. Revertant mutations at all eight positions in the E protein resulted in the highest degree of SA14-14-2 virulence, although this was still lower than that observed in SA14. These results demonstrated the critical role of the viral E protein in controlling JEV virulence and identified the amino acids at the E107 and E138 positions as the key determinants of SA14-14-2 neurovirulence. PMID:28117725

  7. Eugenol, α-pinene and β-caryophyllene from Plectranthus barbatus essential oil as eco-friendly larvicides against malaria, dengue and Japanese encephalitis mosquito vectors.

    PubMed

    Govindarajan, Marimuthu; Rajeswary, Mohan; Hoti, S L; Bhattacharyya, Atanu; Benelli, Giovanni

    2016-02-01

    Mosquito-borne diseases represent a deadly threat for millions of people worldwide. Eco-friendly mosquitocides are a priority. In Ayurvedic medicine, Plectranthus species have been used to treat heart disease, convulsions, spasmodic pain and painful urination. In this research, we evaluated the acute toxicity of essential oil from Plectranthus barbatus and its major constituents, against larvae of the malaria vector Anopheles subpictus, the dengue vector Aedes albopictus and the Japanese encephalitis vector Culex tritaeniorhynchus. The chemical composition of P. barbatus essential oil was analyzed by gas chromatography-mass spectroscopy. Nineteen components were identified. Major constituents were eugenol (31.12%), α-pinene (19.38%) and β-caryophyllene (18.42%). Acute toxicity against early third-instar larvae of An. subpictus, Ae. albopictus and Cx. tritaeniorhynchus was investigated. The essential oil had a significant toxic effect against larvae of An. subpictus, Ae. albopictus and Cx. tritaeniorhynchus, with 50% lethal concentration (LC50) values of 84.20, 87.25 and 94.34 μg/ml and 90% lethal concentration (LC90) values of 165.25, 170.56 and 179.58 μg/ml, respectively. Concerning major constituents, eugenol, α-pinene and β-caryophyllene appeared to be most effective against An. subpictus (LC50 = 25.45, 32.09 and 41.66 μg/ml, respectively), followed by Ae. albopictus (LC50 = 28.14, 34.09 and 44.77 μg/ml, respectively) and Cx. tritaeniorhynchus (LC50 = 30.80, 36.75 and 48.17 μg/ml, respectively). Overall, the chance to use metabolites from P. barbatus essential oil against mosquito vectors seems promising, since they are effective at low doses and could be an advantageous alternative to build newer and safer mosquito control tools.

  8. Hepatitis Virus Infections in Poultry.

    PubMed

    Yugo, Danielle M; Hauck, Ruediger; Shivaprasad, H L; Meng, Xiang-Jin

    2016-09-01

    Viral hepatitis in poultry is a complex disease syndrome caused by several viruses belonging to different families including avian hepatitis E virus (HEV), duck hepatitis B virus (DHBV), duck hepatitis A virus (DHAV-1, -2, -3), duck hepatitis virus Types 2 and 3, fowl adenoviruses (FAdV), and turkey hepatitis virus (THV). While these hepatitis viruses share the same target organ, the liver, they each possess unique clinical and biological features. In this article, we aim to review the common and unique features of major poultry hepatitis viruses in an effort to identify the knowledge gaps and aid the prevention and control of poultry viral hepatitis. Avian HEV is an Orthohepevirus B in the family Hepeviridae that naturally infects chickens and consists of three distinct genotypes worldwide. Avian HEV is associated with hepatitis-splenomegaly syndrome or big liver and spleen disease in chickens, although the majority of the infected birds are subclinical. Avihepadnaviruses in the family of Hepadnaviridae have been isolated from ducks, snow geese, white storks, grey herons, cranes, and parrots. DHBV evolved with the host as a noncytopathic form without clinical signs and rarely progressed to chronicity. The outcome for DHBV infection varies by the host's ability to elicit an immune response and is dose and age dependent in ducks, thus mimicking the pathogenesis of human hepatitis B virus (HBV) infections and providing an excellent animal model for human HBV. DHAV is a picornavirus that causes a highly contagious virus infection in ducks with up to 100% flock mortality in ducklings under 6 wk of age, while older birds remain unaffected. The high morbidity and mortality has an economic impact on intensive duck production farming. Duck hepatitis virus Types 2 and 3 are astroviruses in the family of Astroviridae with similarity phylogenetically to turkey astroviruses, implicating the potential for cross-species infections between strains. Duck astrovirus (DAstV) causes

  9. Co-expression of Japanese encephalitis virus prM-E-NS1 antigen with granulocyte-macrophage colony-stimulating factor enhances humoral and anti-virus immunity after DNA vaccination.

    PubMed

    Gao, Na; Chen, Wei; Zheng, Qun; Fan, Dong-ying; Zhang, Jun-lei; Chen, Hui; Gao, George F; Zhou, De-shan; An, Jing

    2010-03-10

    Japanese encephalitis virus (JEV) is an agent of Japanese encephalitis, and granulocyte-macrophage colony-stimulating factor (GM-CSF) is an attractive DNA vaccine adjuvant for its antigen presentation. In the present study, we have constructed DNA vaccines that carried JEV prM-E-NS1 genes with or without the GM-CSF gene. Immunization with the bicistronic plasmid pCAG-JEGM that co-expresses GM-CSF and viral prM-E-NS1, resulted in the highest IgG response and sufficient protection against virus-challenged BALB/c mice. However, much to our surprise, co-inoculation of the GM-CSF plasmid with the pCAG-JE plasmid expressing viral prM-E-NS1 lead to a low antibody titer and a relatively low survival rate. Moreover, anamnestic antibody-mediated protection played a dominant role in the mice JEV challenge model, according to the enhancement of post-challenge neutralizing antibody titers and further adoptive transfer experiments. Taken together, this study should encourage further development of JEV DNA vaccine strategies and caution against the use of cytokines as an adjuvant.

  10. Life-Threatening Sochi Virus Infections, Russia.

    PubMed

    Kruger, Detlev H; Tkachenko, Evgeniy A; Morozov, Vyacheslav G; Yunicheva, Yulia V; Pilikova, Olga M; Malkin, Gennadiy; Ishmukhametov, Aydar A; Heinemann, Patrick; Witkowski, Peter T; Klempa, Boris; Dzagurova, Tamara K

    2015-12-01

    Sochi virus was recently identified as a new hantavirus genotype carried by the Black Sea field mouse, Apodemus ponticus. We evaluated 62 patients in Russia with Sochi virus infection. Most clinical cases were severe, and the case-fatality rate was as high as 14.5%.

  11. Mental Status after West Nile Virus Infection

    PubMed Central

    Sadek, Joseph; Pergam, Steven; Echevarria, Leonor A.; Davis, Larry E.; Goade, Diane; Harnar, Joanne; Nofchissey, Robert A.; Sewel, C. Mack; Ettestad, Paul

    2006-01-01

    Mental status after acute West Nile virus infection has not been examined objectively. We compared Telephone Interview for Cognitive Status scores of 116 patients with West Nile fever or West Nile neuroinvasive disease. Mental status was poorer and cognitive complaints more frequent with West Nile neuroinvasive disease (p = 0.005). PMID:16965710

  12. Pathogenesis of Lassa Virus Infection in Guinea Pigs

    DTIC Science & Technology

    1982-08-01

    virus , an arenavirus distantly related to Lassa Lassa fever ...other arenaviruses in animal models (5. 6). In VOL. 37, 1982 LASSA VIRUS INFECTION IN GUINEA PIGS 777S[ iU FIG. 6. (A) Lassa viral antigens in...resem- ent with the hemoconcentration associated with bles human and primate Lassa virus infection other human hemorrhagic fever virus infections. than

  13. Japanese encephalitis protein vaccine candidates expressing neutralizing epitope and M.T hsp70 induce virus-specific memory B cells and long-lasting antibodies in swine.

    PubMed

    Fei-fei, Ge; Jian, Wang; Feng, Xu; Li-ping, Sheng; Quan-yun, Sun; Jin-ping, Zhou; Pu-yan, Chen; Pei-hong, Liu

    2008-10-16

    Swine are an important amplifier of Japanese encephalitis (JE) virus in the paradomestic environment. In this study, two JE protein vaccine candidates were evaluated for immunogenicity in swine. Both vaccine plasmids are based on a prokaryotic vector pET-32a(+). One plasmid, designated pET-32a(+)-epitope, encode a cassette consisting of a neutralizing epitope on envelope (E) protein of JE virus, whereas the other plasmid, designated pET-32a(+)-epitope-hsp70, express the fusion protein of the epitope and M.T hsp70. Some differences were detected in the immunogenicity of these two proteins in swine. Swine immunized twice with 2000pmol of the neutralizing epitope or the fusion protein developed neutralizing antibody titers of respectively, 154 and 300, and anti-neutralizing epitope antibody titers of 10(4.25) and 10(6.0) by 3 weeks after the second immunization. In addition, swine immunized with the neutralizing epitope emulsified with adjuvant S206 or with imported mineral oil and Tween-80 induced neutralizing antibody titers of 196 and 244, and anti-neutralizing epitope antibody titers of 10(5.25) or 10(5.6) at the same time point. However, swine administered two doses of a commercial JE vaccine (attenuated virus preparation; JEV SA14-14-2 strain) developed less favorable antibody responses with neutralizing antibody titer 40 and anti-neutralizing epitope antibody titers 10(3.7). The anamnestic response was followed by monitoring titers 1 week after boosting with a viral antigen; swine immunized twice with the fusion protein showed a 177-fold increase in anti-neutralizing epitope titer, indicating a strong recall of the antibody response. The animals maintained detectable levels of anti-neutralizing epitope antibody for at least 105 days after two immunizations, indicating that these four protein antigens are able to stimulate virus-specific memory B cells and long-lasting antibodies at higher levels than is achieved using a current commercial attenuated JEV vaccine

  14. Insecticide resistance spectra and resistance mechanisms in populations of Japanese encephalitis vector mosquitoes, Culex tritaeniorhynchus and Cx. gelidus, in Sri Lanka.

    PubMed

    Karunaratne, S H; Hemingway, J

    2000-12-01

    Culex tritaeniorhynchus Giles and Cx. gelidus Theobald (Diptera: Culicidae), both vectors of Japanese encephalitis, were collected in 1984 and 1998 from two disease endemic localities in Sri Lanka: Anaradhapura and Kandy. Using wild-caught adult mosquitoes from light traps, log dosage-probit mortality curves for insecticide bioassays were obtained for three insecticides: malathion (organophosphate), propoxur (carbamate) and permethrin (pyrethroid). LD50 values showed that, in 1998, Cx. tritaeniorhynchus was -100-fold more resistant to malathion and 10-fold more resistant to propoxur than was Cx. gelidus. This difference was attributed to Cx. tritaeniorhynchus breeding mostly in irrigated rice paddy fields, where it would have been exposed to pesticide selection pressure, whereas Cx. gelidus breeds in other types of aquatic habitats less prone to pesticide applications. Resistance in Cx. tritaeniorhynchus increased between 1984 and 1998, whereas Cx. gelidus remained predominantly susceptible. Propoxur inhibition of acetylcholinesterase (AChE) activity (the target site of organophosphates and carbamates) indicated that in 1998, frequencies of insensitive AChE-based resistance were 9% in Cx. gelidus and 2-23% in Cx. tritaeniorhynchus, whereas in 1984 this resistance mechanism was detected only in 2% of the latter species from Anaradhapura. The AChE inhibition coefficient (ki) with propoxur was 1.86+/-0.24 x 10(5) M(-)1 min(-1) for Cx. tritaeniorhynchus from Anaradhapura in 1998. Both species were tested for activity levels of detoxifying glutathione S-transferases (GSTs) and malathion-specific as well as general carboxylesterases. High activities of GSTs and carboxylesterases were detected in Cx. tritaeniorhynchus but not Cx. gelidus. Malathion-specific carboxylesterase was absent from both species. Native polyacrylamide gel electrophoresis resolved two elevated general carboxylesterases, CtrEstbeta1 and CtrEstalpha1, from Cx. tritaeniorhynchus and none from Cx

  15. The C Terminus of the Core β-Ladder Domain in Japanese Encephalitis Virus Nonstructural Protein 1 Is Flexible for Accommodation of Heterologous Epitope Fusion

    PubMed Central

    Yen, Li-Chen; Liao, Jia-Teh; Lee, Hwei-Jen; Chou, Wei-Yuan; Chen, Chun-Wei; Lin, Yi-Ling

    2015-01-01

    ABSTRACT NS1 is the only nonstructural protein that enters the lumen of the endoplasmic reticulum (ER), where NS1 is glycosylated, forms a dimer, and is subsequently secreted during flavivirus replication as dimers or hexamers, which appear to be highly immunogenic to the infected host, as protective immunity can be elicited against homologous flavivirus infections. Here, by using a trans-complementation assay, we identified the C-terminal end of NS1 derived from Japanese encephalitis virus (JEV), which was more flexible than other regions in terms of housing foreign epitopes without a significant impact on virus replication. This mapped flexible region is located in the conserved tip of the core β-ladder domain of the multimeric NS1 structure and is also known to contain certain linear epitopes, readily triggering specific antibody responses from the host. Despite becoming attenuated, recombinant JEV with insertion of a neutralizing epitope derived from enterovirus 71 (EV71) into the C-terminal end of NS1 not only could be normally released from infected cells, but also induced dual protective immunity for the host to counteract lethal challenge with either JEV or EV71 in neonatal mice. These results indicated that the secreted multimeric NS1 of flaviviruses may serve as a natural protein carrier to render epitopes of interest more immunogenic in the C terminus of the core β-ladder domain. IMPORTANCE The positive-sense RNA genomes of mosquito-borne flaviviruses appear to be flexible in terms of accommodating extra insertions of short heterologous antigens into their virus genes. Here, we illustrate that the newly identified C terminus of the core β-ladder domain in NS1 could be readily inserted into entities such as EV71 epitopes, and the resulting NS1-epitope fusion proteins appeared to maintain normal virus replication, secretion ability, and multimeric formation from infected cells. Nonetheless, such an insertion attenuated the recombinant JEV in mice

  16. Dengue encephalitis

    PubMed Central

    Borawake, Kapil; Prayag, Parikshit; Wagh, Atul; Dole, Swati

    2011-01-01

    We report a case of dengue fever with features of encephalitis. The diagnosis of dengue was confirmed by the serum antibodies to dengue and the presence of a dengue antigen in the cerebrospinal fluid. This patient had characteristic magnetic resonance imaging brain findings, mainly involving the bilateral thalami, with hemorrhage. Dengue is not primarily a neurotropic virus and encephalopathy is a common finding in Dengue. Hence various other etiological possibilities were considered before concluding this as a case of Dengue encephalitis. This case explains the importance of considering the diagnosis of dengue encephalitis in appropriate situations. PMID:22013316

  17. Uterine adenocarcinoma with feline leukemia virus infection.

    PubMed

    Cho, Sung-Jin; Lee, Hyun-A; Hong, Sunhwa; Kim, Okjin

    2011-12-01

    Feline endometrial adenocarcinomas are uncommon malignant neoplasms that have been poorly characterized to date. In this study, we describe a uterine adenocarcinoma in a Persian cat with feline leukemia virus infection. At the time of presentation, the cat, a female Persian chinchilla, was 2 years old. The cat underwent surgical ovariohystectomy. A cross-section of the uterine wall revealed a thickened uterine horn. The cat tested positive for feline leukemia virus as detected by polymerase chain reaction. Histopathological examination revealed uterine adenocarcinoma that had metastasized to the omentum, resulting in thickening and the formation of inflammatory lesions. Based on the histopathological findings, this case was diagnosed as a uterine adenocarcinoma with abdominal metastasis. To the best of our knowledge, this is the first report of a uterine adenocarcinoma with feline leukemia virus infection.

  18. Virus Infections in the Nervous System

    PubMed Central

    Koyuncu, Orkide O.; Hogue, Ian B.; Enquist, Lynn W.

    2013-01-01

    Virus infections usually begin in peripheral tissues and can invade the mammalian nervous system (NS), spreading into the peripheral (PNS) and more rarely the central nervous systems (CNS). The CNS is protected from most virus infections by effective immune responses and multi-layer barriers. However, some viruses enter the NS with high efficiency via the bloodstream or by directly infecting nerves that innervate peripheral tissues, resulting in debilitating direct and immune-mediated pathology. Most viruses in the NS are opportunistic or accidental pathogens, but a few, most notably the alpha herpesviruses and rabies virus, have evolved to enter the NS efficiently and exploit neuronal cell biology. Remarkably, the alpha herpesviruses can establish quiescent infections in the PNS, with rare but often fatal CNS pathology. Here we review how viruses gain access to and spread in the well-protected CNS, with particular emphasis on alpha herpesviruses, which establish and maintain persistent NS infections. PMID:23601101

  19. Interferon-γ Inhibits Ebola Virus Infection

    PubMed Central

    Rhein, Bethany A.; Powers, Linda S.; Rogers, Kai; Anantpadma, Manu; Singh, Brajesh K.; Sakurai, Yasuteru; Bair, Thomas; Miller-Hunt, Catherine; Sinn, Patrick; Davey, Robert A.

    2015-01-01

    Ebola virus outbreaks, such as the 2014 Makona epidemic in West Africa, are episodic and deadly. Filovirus antivirals are currently not clinically available. Our findings suggest interferon gamma, an FDA-approved drug, may serve as a novel and effective prophylactic or treatment option. Using mouse-adapted Ebola virus, we found that murine interferon gamma administered 24 hours before or after infection robustly protects lethally-challenged mice and reduces morbidity and serum viral titers. Furthermore, we demonstrated that interferon gamma profoundly inhibits Ebola virus infection of macrophages, an early cellular target of infection. As early as six hours following in vitro infection, Ebola virus RNA levels in interferon gamma-treated macrophages were lower than in infected, untreated cells. Addition of the protein synthesis inhibitor, cycloheximide, to interferon gamma-treated macrophages did not further reduce viral RNA levels, suggesting that interferon gamma blocks life cycle events that require protein synthesis such as virus replication. Microarray studies with interferon gamma-treated human macrophages identified more than 160 interferon-stimulated genes. Ectopic expression of a select group of these genes inhibited Ebola virus infection. These studies provide new potential avenues for antiviral targeting as these genes that have not previously appreciated to inhibit negative strand RNA viruses and specifically Ebola virus infection. As treatment of interferon gamma robustly protects mice from lethal Ebola virus infection, we propose that interferon gamma should be further evaluated for its efficacy as a prophylactic and/or therapeutic strategy against filoviruses. Use of this FDA-approved drug could rapidly be deployed during future outbreaks. PMID:26562011

  20. Imported Mayaro virus infection in the Netherlands.

    PubMed

    Hassing, Robert-Jan; Leparc-Goffart, Isabelle; Blank, Sybrandus N; Thevarayan, Subashini; Tolou, Hugues; van Doornum, Gerard; van Genderen, Perry J

    2010-10-01

    A Dutch couple, presenting with persisting arthralgias, temporary fever and rash after a stay in Surinam were diagnosed with Mayaro virus infection. Mayaro virus is a relatively unknown South American Alphavirus responsible for dengue-like clinical features and persisting arthralgias. An important, but probably underappreciated cross-reactivity with other Alphaviruses like Chikungunya virus is present, which may become of clinical importance in the event the various Alphaviruses will have overlapping geographical distributions and in seroprevalence studies.

  1. Interferon-γ Inhibits Ebola Virus Infection.

    PubMed

    Rhein, Bethany A; Powers, Linda S; Rogers, Kai; Anantpadma, Manu; Singh, Brajesh K; Sakurai, Yasuteru; Bair, Thomas; Miller-Hunt, Catherine; Sinn, Patrick; Davey, Robert A; Monick, Martha M; Maury, Wendy

    2015-01-01

    Ebola virus outbreaks, such as the 2014 Makona epidemic in West Africa, are episodic and deadly. Filovirus antivirals are currently not clinically available. Our findings suggest interferon gamma, an FDA-approved drug, may serve as a novel and effective prophylactic or treatment option. Using mouse-adapted Ebola virus, we found that murine interferon gamma administered 24 hours before or after infection robustly protects lethally-challenged mice and reduces morbidity and serum viral titers. Furthermore, we demonstrated that interferon gamma profoundly inhibits Ebola virus infection of macrophages, an early cellular target of infection. As early as six hours following in vitro infection, Ebola virus RNA levels in interferon gamma-treated macrophages were lower than in infected, untreated cells. Addition of the protein synthesis inhibitor, cycloheximide, to interferon gamma-treated macrophages did not further reduce viral RNA levels, suggesting that interferon gamma blocks life cycle events that require protein synthesis such as virus replication. Microarray studies with interferon gamma-treated human macrophages identified more than 160 interferon-stimulated genes. Ectopic expression of a select group of these genes inhibited Ebola virus infection. These studies provide new potential avenues for antiviral targeting as these genes that have not previously appreciated to inhibit negative strand RNA viruses and specifically Ebola virus infection. As treatment of interferon gamma robustly protects mice from lethal Ebola virus infection, we propose that interferon gamma should be further evaluated for its efficacy as a prophylactic and/or therapeutic strategy against filoviruses. Use of this FDA-approved drug could rapidly be deployed during future outbreaks.

  2. Zika Virus Infection: Current Concerns and Perspectives.

    PubMed

    Maharajan, Mari Kannan; Ranjan, Aruna; Chu, Jian Feng; Foo, Wei Lim; Chai, Zhi Xin; Lau, Eileen YinYien; Ye, Heuy Mien; Theam, Xi Jin; Lok, Yen Ling

    2016-12-01

    The Zika virus outbreaks highlight the growing importance need for a reliable, specific and rapid diagnostic device to detect Zika virus, as it is often recognized as a mild disease without being identified. Many Zika virus infection cases have been misdiagnosed or underreported because of the non-specific clinical presentation. The aim of this review was to provide a critical and comprehensive overview of the published peer-reviewed evidence related to clinical presentations, various diagnostic methods and modes of transmission of Zika virus infection, as well as potential therapeutic targets to combat microcephaly. Zika virus is mainly transmitted through bites from Aedes aegypti mosquito. It can also be transmitted through blood, perinatally and sexually. Pregnant women are advised to postpone or avoid travelling to areas where active Zika virus transmission is reported, as this infection is directly linked to foetal microcephaly. Due to the high prevalence of Guillain-Barre syndrome and microcephaly in the endemic area, it is vital to confirm the diagnosis of Zika virus. Zika virus infection had been declared as a public health emergency and of international concern by the World Health Organisation. Governments and agencies should play an important role in terms of investing time and resources to fundamentally understand this infection so that a vaccine can be developed besides raising awareness.

  3. Replication of Japanese Encephalitis Virus.

    DTIC Science & Technology

    1980-12-10

    division , school, laboratory, etc., of the author. List city, state, and ZIP Code. Block 10 Program Element, Project, Task Area, and Work Unit Numbers...largely of smooth and some rough intracytoplasmic membranes. ....4’ .... ..... . 14 Table 4. Phospholipid distribution in celular membranes and virions

  4. Fatal Infection with Murray Valley Encephalitis Virus Imported from Australia to Canada, 2011

    PubMed Central

    Niven, Daniel J.; Afra, Kevin; Iftinca, Mircea; Tellier, Raymond; Fonseca, Kevin; Kramer, Andreas; Safronetz, David; Holloway, Kimberly; Drebot, Michael

    2017-01-01

    Murray Valley encephalitis virus (MVEV), a flavivirus belonging to the Japanese encephalitis serogroup, can cause severe clinical manifestations in humans. We report a fatal case of MVEV infection in a young woman who returned from Australia to Canada. The differential diagnosis for travel-associated encephalitis should include MVEV, particularly during outbreak years. PMID:28098530

  5. Immune responses and Lassa virus infection.

    PubMed

    Russier, Marion; Pannetier, Delphine; Baize, Sylvain

    2012-11-05

    Lassa fever is a hemorrhagic fever endemic to West Africa and caused by Lassa virus, an Old World arenavirus. It may be fatal, but most patients recover from acute disease and some experience asymptomatic infection. The immune mechanisms associated with these different outcomes have not yet been fully elucidated, but considerable progress has recently been made, through the use of in vitro human models and nonhuman primates, the only relevant animal model that mimics the pathophysiology and immune responses induced in patients. We discuss here the roles of the various components of the innate and adaptive immune systems in Lassa virus infection and in the control of viral replication and pathogenesis.

  6. Virus infection speeds: Theory versus experiment

    NASA Astrophysics Data System (ADS)

    Amor, Daniel R.; Fort, Joaquim

    2010-12-01

    In order to explain the speed of Vesicular Stomatitis Virus (VSV) infections, we develop a simple model that improves previous approaches to the propagation of virus infections. For VSV infections, we find that the delay time elapsed between the adsorption of a viral particle into a cell and the release of its progeny has a very important effect. Moreover, this delay time makes the adsorption rate essentially irrelevant in order to predict VSV infection speeds. Numerical simulations are in agreement with the analytical results. Our model satisfactorily explains the experimentally measured speeds of VSV infections.

  7. Small molecule inhibitors of ebola virus infection.

    PubMed

    Picazo, Edwige; Giordanetto, Fabrizio

    2015-02-01

    Ebola viruses are extremely virulent and highly transmissible. They are responsible for sporadic outbreaks of severe hemorrhagic fevers with human mortality rates of up to 90%. No prophylactic or therapeutic treatments in the form of vaccine, biologicals or small molecule, currently exist. Yet, a wealth of antiviral research on ebola virus is being generated and potential inhibitors have been identified in biological screening and medicinal chemistry programs. Here, we detail the state-of-the-art in small molecule inhibitors of ebola virus infection, with >60 examples, including approved drugs, compounds currently in clinical trials, and more exploratory leads, and summarize the associated in vitro and in vivo evidence for their effectiveness.

  8. Update on oral herpes virus infections.

    PubMed

    Balasubramaniam, Ramesh; Kuperstein, Arthur S; Stoopler, Eric T

    2014-04-01

    Oral herpes virus infections (OHVIs) are among the most common mucosal disorders encountered by oral health care providers. These infections can affect individuals at any age, from infants to the elderly, and may cause significant pain and dysfunction. Immunosuppressed patients may be at increased risk for serious and potential life-threatening complications caused by OHVIs. Clinicians may have difficulty in diagnosing these infections because they can mimic other conditions of the oral mucosa. This article provides oral health care providers with clinically relevant information regarding etiopathogenesis, diagnosis, and management of OHVIs.

  9. METHODS USED TO STUDY RESPIRATORY VIRUS INFECTION

    PubMed Central

    Flaño, Emilio; Jewell, Nancy A.; Durbin, Russell K.; Durbin, Joan E.

    2009-01-01

    This unit describes protocols for infecting the mouse respiratory tract, and assaying virus replication and host response in the lung. Respiratory infections are the leading cause of acute illness worldwide, affecting mostly infants and children in developing countries. The purpose of this unit is to provide the readers with a basic strategy and protocols to study the pathogenesis and immunology of respiratory virus infection using the mouse as an animal model. The procedures include: (i) basic techniques for mouse infection, tissue sampling and preservation, (ii) determination of viral titers, isolation and analysis of lymphocytes and dendritic cells using flow-cytometry, and (iii) lung histology, immunohistochemistry and in situ hybridization. PMID:19499505

  10. Encephalitis awareness.

    PubMed

    Easton, Ava

    2017-03-01

    Last week we marked the 4th World Encephalitis Day, a global campaign with two primary aims. The first is to acknowledge the experiences of survivors of this devastating neurological condition and their family members, while the second is to raise much-needed awareness among the public.

  11. Plant virus infections control stomatal development

    NASA Astrophysics Data System (ADS)

    Murray, Rose R.; Emblow, Mark S. M.; Hetherington, Alistair M.; Foster, Gary D.

    2016-09-01

    Stomata are important regulators of carbon dioxide uptake and transpirational water loss. They also represent points of vulnerability as bacterial and fungal pathogens utilise this natural opening as an entry portal, and thus have an increasingly complex relationship. Unlike the situation with bacterial and fungal pathogens, we know very little about the role of stomata in viral infection. Here we report findings showing that viral infection influences stomatal development in two susceptible host systems (Nicotiana tabacum with TMV (Tobacco mosaic virus), and Arabidopsis thaliana with TVCV (Turnip vein-clearing virus)), but not in resistant host systems (Nicotiana glutinosa and Chenopodium quinoa with TMV). Virus infected plants had significantly lower stomatal indices in systemic leaves of susceptible systems; N. tabacum 9.8% reduction and A. thaliana 12.3% reduction, but not in the resistant hosts. Stomatal density in systemic leaves was also significantly reduced in virus infected A. thaliana by 19.6% but not in N. tabacum or the resistant systems. In addition, transpiration rate was significantly reduced in TMV infected N. tabacum.

  12. Plant virus infections control stomatal development

    PubMed Central

    Murray, Rose R.; Emblow, Mark S. M.; Hetherington, Alistair M.; Foster, Gary D.

    2016-01-01

    Stomata are important regulators of carbon dioxide uptake and transpirational water loss. They also represent points of vulnerability as bacterial and fungal pathogens utilise this natural opening as an entry portal, and thus have an increasingly complex relationship. Unlike the situation with bacterial and fungal pathogens, we know very little about the role of stomata in viral infection. Here we report findings showing that viral infection influences stomatal development in two susceptible host systems (Nicotiana tabacum with TMV (Tobacco mosaic virus), and Arabidopsis thaliana with TVCV (Turnip vein-clearing virus)), but not in resistant host systems (Nicotiana glutinosa and Chenopodium quinoa with TMV). Virus infected plants had significantly lower stomatal indices in systemic leaves of susceptible systems; N. tabacum 9.8% reduction and A. thaliana 12.3% reduction, but not in the resistant hosts. Stomatal density in systemic leaves was also significantly reduced in virus infected A. thaliana by 19.6% but not in N. tabacum or the resistant systems. In addition, transpiration rate was significantly reduced in TMV infected N. tabacum. PMID:27687773

  13. Mayaro virus infection, Amazon Basin region, Peru, 2010-2013.

    PubMed

    Halsey, Eric S; Siles, Crystyan; Guevara, Carolina; Vilcarromero, Stalin; Jhonston, Erik J; Ramal, Cesar; Aguilar, Patricia V; Ampuero, Julia S

    2013-11-01

    During 2010-2013, we recruited 16 persons with confirmed Mayaro virus infection in the Peruvian Amazon to prospectively follow clinical symptoms and serologic response over a 12-month period. Mayaro virus infection caused long-term arthralgia in more than half, similar to reports of other arthritogenic alphaviruses.

  14. Zika virus infection acquired during brief travel to Indonesia.

    PubMed

    Kwong, Jason C; Druce, Julian D; Leder, Karin

    2013-09-01

    Zika virus infection closely resembles dengue fever. It is possible that many cases are misdiagnosed or missed. We report a case of Zika virus infection in an Australian traveler who returned from Indonesia with fever and rash. Further case identification is required to determine the evolving epidemiology of this disease.

  15. Development of therapeutics for treatment of Ebola virus infection.

    PubMed

    Li, Haoyang; Ying, Tianlei; Yu, Fei; Lu, Lu; Jiang, Shibo

    2015-02-01

    Ebola virus infection can cause Ebola virus disease (EVD). Patients usually show severe symptoms, and the fatality rate can reach up to 90%. No licensed medicine is available. In this review, development of therapeutics for treatment of Ebola virus infection and EVD will be discussed.

  16. Severe Thrombocytopenia after Zika Virus Infection, Guadeloupe, 2016

    PubMed Central

    Boyer Chammard, Timothée; Schepers, Kinda; Breurec, Sébastien; Messiaen, Thierry; Destrem, Anne-Laure; Mahevas, Matthieu; Soulillou, Adrien; Janaud, Ludovic; Curlier, Elodie; Herrmann-Storck, Cécile

    2017-01-01

    Severe thrombocytopenia during or after the course of Zika virus infection has been rarely reported. We report 7 cases of severe thrombocytopenia and hemorrhagic signs and symptoms in Guadeloupe after infection with this virus. Clinical course and laboratory findings strongly suggest a causal link between Zika virus infection and immune-mediated thrombocytopenia. PMID:27997330

  17. Severe Thrombocytopenia after Zika Virus Infection, Guadeloupe, 2016.

    PubMed

    Boyer Chammard, Timothée; Schepers, Kinda; Breurec, Sébastien; Messiaen, Thierry; Destrem, Anne-Laure; Mahevas, Matthieu; Soulillou, Adrien; Janaud, Ludovic; Curlier, Elodie; Herrmann-Storck, Cécile; Hoen, Bruno

    2017-04-01

    Severe thrombocytopenia during or after the course of Zika virus infection has been rarely reported. We report 7 cases of severe thrombocytopenia and hemorrhagic signs and symptoms in Guadeloupe after infection with this virus. Clinical course and laboratory findings strongly suggest a causal link between Zika virus infection and immune-mediated thrombocytopenia.

  18. Vaccinia virus infections in martial arts gym, Maryland, USA, 2008.

    PubMed

    Hughes, Christine M; Blythe, David; Li, Yu; Reddy, Ramani; Jordan, Carol; Edwards, Cindy; Adams, Celia; Conners, Holly; Rasa, Catherine; Wilby, Sue; Russell, Jamaal; Russo, Kelly S; Somsel, Patricia; Wiedbrauk, Danny L; Dougherty, Cindy; Allen, Christopher; Frace, Mike; Emerson, Ginny; Olson, Victoria A; Smith, Scott K; Braden, Zachary; Abel, Jason; Davidson, Whitni; Reynolds, Mary; Damon, Inger K

    2011-04-01

    Vaccinia virus is an orthopoxvirus used in the live vaccine against smallpox. Vaccinia virus infections can be transmissible and can cause severe complications in those with weakened immune systems. We report on a cluster of 4 cases of vaccinia virus infection in Maryland, USA, likely acquired at a martial arts gym.

  19. Isolated polio-like syndrome after tick-borne encephalitis presenting with acute hyperckemia.

    PubMed

    Zambito Marsala, Sandro; Francavilla, Ermenegildo; Gioulis, Manuela; Candeago, Rosa Maria; Mondardini, Valeria; Gentile, Manrico; Ferracci, Franco; Guzzo, Francesco; Granata, Carmela; Marchini, Corrado

    2012-06-01

    Tick borne encephalitis virus infection usually shows a biphasic course. In the first stage of illness symptoms are similar to a flu-like syndrome, then after a defervescence period, fever may represent with neurological manifestations ranging from mild meningitis to severe encephalomyelitis. We report the clinical case of an adult man presented with an acute proximal hyposthenia, severe hyperckemia, clinical and laboratoristic evidence of acute tick borne virus infection. This virus has a favourite tropism for the anterior horn cells of the cervical spine segment. Polio-like syndrome, usually affecting the upper limbs, is the clinical phenotype of an infection of the cervical motoneurons. Usually myelitis is associated to severe encephalitis and a complete diagnosis may be difficult in comatose patients. Rarely, an isolated polio-like syndrome may be the sole neurological complication of tick-borne encephalitis.

  20. Serologic evidence for West Nile virus infection in birds in the New York City vicinity during an outbreak in 1999.

    PubMed

    Komar, N; Panella, N A; Burns, J E; Dusza, S W; Mascarenhas, T M; Talbot, T O

    2001-01-01

    As part of an investigation of an encephalitis outbreak in New York City, we sampled 430 birds, representing 18 species in four orders, during September 13-23, 1999, in Queens and surrounding counties. Overall, 33% were positive for West Nile (WN) virus-neutralizing antibodies, and 0.5% were positive for St. Louis encephalitis virus-neutralizing antibodies. By county, Queens had the most seropositive birds for WN virus (50%); species with the greatest seropositivity for WN virus (sample sizes were at least six) were Domestic Goose, Domestic Chicken, House Sparrow, Canada Goose, and Rock Dove. One sampled bird, a captive adult Domestic Goose, showed signs of illness; WN virus infection was confirmed. Our results support the concept that chickens and House Sparrows are good arbovirus sentinels. This study also implicates the House Sparrow as an important vertebrate reservoir host.

  1. Recurrent Transcortical Motor Aphasia—Another CNS Infectious Syndrome Associated with Herpes Virus Infection

    PubMed Central

    Govindarajan, Raghav; Salgado, Efrain

    2016-01-01

    Herpes simplex encephalitis is an acute/subacute illness that causes both general and focal signs of cerebral dysfunction with fever, headache, and confusion as cardinal features. Recurrent herpes simplex meningitis, also known as Mollaret’s meningitis, is another manifestation of central nervous system herpetic infection with recurrent episodes of fever, headache, and nuchal rigidity associated with cerebrospinal fluid (CSF) evidence of active herpes simplex infection. Bell’s palsy is yet another manifestation of a herpes virus infection in at least some reported cases documented by CSF analysis. We report a case of a 70-year-old male who presented with acute transcortical motor aphasia initiating a stroke work-up that was negative. Physical examination revealed genital vesicles, and the CSF was consistent with active herpes simplex infection. PMID:26958155

  2. Spinal cord toxoplasmosis in human immunodeficiency virus infection/acquired immunodeficiency syndrome.

    PubMed

    García-García, Concepción; Castillo-Álvarez, Federico; Azcona-Gutiérrez, José M; Herraiz, María J; Ibarra, Valvanera; Oteo, José A

    2015-05-01

    Neurological complications in patients with human immunodeficiency virus infection/acquired immunodeficiency syndrome (HIV/AIDS) are still common, even in the era of highly active antiretroviral therapy. Opportunistic infections, immune reconstitution, the virus itself, antiretroviral drugs and neurocognitive disorders have to be considered when establishing the differential diagnosis. Toxoplasmic encephalitis remains the major cause of space-occupying lesions in the brain of patients with HIV/AIDS; however, spinal cord involvement has been reported infrequently. Here, we review spinal cord toxoplasmosis in HIV infection and illustrate the condition with a recent case from our hospital. We suggest that most patients with HIV/AIDS and myelitis with enhanced spine lesions, multiple brain lesions and positive serology for Toxoplasma gondii should receive immediate empirical treatment for toxoplasmosis, and a biopsy should be performed in those cases without clinical improvement or with deterioration.

  3. Encephalitis (For Parents)

    MedlinePlus

    ... West Nile encephalitis, St. Louis encephalitis, and Western Equine encephalitis. Over the last several years in the ... to prevent further swelling of the brain. Because antibiotics aren't effective against viruses, they aren't ...

  4. Experimental biology and pathogenesis of Junin virus infection in animals and man*

    PubMed Central

    Weissenbacher, M. C.; De Guerrero, L. B.; Boxaca, M. C.

    1975-01-01

    A fatal disease resembling Argentine haemorrhagic fever of man has been produced in guinea-pigs and mice by inoculation with Junin virus. Infected guinea-pigs show macroscopic and microscopic haemorrhagic lesions, marked bone marrow changes, decreased leukocytes and platelets in the peripheral blood, and impairment of immunological response. This response permits differentiation between pathogenic (XJ) and attenuated (XJ Cl3) strains. Guinea-pigs inoculated with the XJ Cl3 strain develop an inapparent infection accompanied by slight haematological changes, the appearance of antibody, and protection against challenge with the pathogenic strain. The attenuated strain has been used successfully as an immunizing antigen in 636 human volunteers. Guinea-pigs infected with Tacaribe virus show cross-protection against Junin virus, with the presence of heterologous neutralizing antibodies. Suckling mice infected with Junin virus develop a typical viral encephalitis; the pathogenicity of the virus decreases with increasing age of the mice. Experiments with thymectomized mice and with mice treated with antithymocyte serum suggest that the pathogenicity of Junin virus in this host is related to the integrity of the thymus-dependent immune system. There is evidence that humoral antibodies do not play any role in the development of the encephalitic lesions but rather protect mice against Junin virus infection. A recent serological survey among laboratory workers and inhabitants of the endemic area has demonstrated the presence of inapparent infection with Junin virus. PMID:182401

  5. Anti-NMDA Receptor Encephalitis and Vaccination

    PubMed Central

    Wang, Hsiuying

    2017-01-01

    Anti-N-methyl-d-aspartate (Anti-NMDA) receptor encephalitis is an acute autoimmune neurological disorder. The cause of this disease is often unknown, and previous studies revealed that it might be caused by a virus, vaccine or tumor. It occurs more often in females than in males. Several cases were reported to be related to vaccination such as the H1N1 vaccine and tetanus/diphtheria/pertussis and polio vaccines. In this study, we reported an anti-NMDA receptor encephalitis case that may be caused by Japanese encephalitis vaccination. To investigate the association between anti-NMDA receptor encephalitis and vaccination, we analyzed the phylogenetic relationship of the microRNAs, which significantly regulate these vaccine viruses or bacteria, and the phylogenetic relationship of these viruses and bacteria. This reveals that anti-NMDA receptor encephalitis may be caused by Japanese encephalitis vaccination, as well as H1N1 vaccination or tetanus/diphtheria/pertussis and polio vaccinations, from the phylogenetic viewpoint. PMID:28106787

  6. Anti-NMDA Receptor Encephalitis and Vaccination.

    PubMed

    Wang, Hsiuying

    2017-01-18

    Anti-N-methyl-d-aspartate (Anti-NMDA) receptor encephalitis is an acute autoimmune neurological disorder. The cause of this disease is often unknown, and previous studies revealed that it might be caused by a virus, vaccine or tumor. It occurs more often in females than in males. Several cases were reported to be related to vaccination such as the H1N1 vaccine and tetanus/diphtheria/pertussis and polio vaccines. In this study, we reported an anti-NMDA receptor encephalitis case that may be caused by Japanese encephalitis vaccination. To investigate the association between anti-NMDA receptor encephalitis and vaccination, we analyzed the phylogenetic relationship of the microRNAs, which significantly regulate these vaccine viruses or bacteria, and the phylogenetic relationship of these viruses and bacteria. This reveals that anti-NMDA receptor encephalitis may be caused by Japanese encephalitis vaccination, as well as H1N1 vaccination or tetanus/diphtheria/pertussis and polio vaccinations, from the phylogenetic viewpoint.

  7. 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.

  8. Herpes simplex type-1 virus infection.

    PubMed

    Huber, Michaell A

    2003-06-01

    Oral infection caused by the herpes simplex virus represents one of the more common conditions the dental practitioner will be called upon to manage. Unique in its ability to establish latency and undergo subsequent recurrence, it is an ubiquitous infectious agent for which a cure does not exist. For the immunocompetent patient, herpes virus simplex infection typically represents nothing more than a nuisance. However, for the immunocompromised patient, this infection is associated with increased morbidity and mortality. Recently introduced antiviral drug regimens may reduce the morbidity and potential mortality of the herpes simplex virus, especially in immunocompromised patients. The value of antiviral therapy in the management of recurrent herpes simplex virus infection in the immunocompetent patient remains an area of contentious debate.

  9. [Hepatitis C virus infection and alcohol].

    PubMed

    Campollo, Octavio

    2002-10-01

    It was thought that HCV infection was very frequent among alcoholics; some even though that this disease affected nearly 35% of this group. Now there seems to be a consensus among the main investigator groups that the correlation of hepatitis C and alcohol increases the risk of complications, cirrhosis and liver cancer included. Moreover, it's now certain that among patients with HCV infection, alcohol consumption increases the risk of death from live diseases during the first 10 years of the disease. Alcoholism is also considered a predisposing factor for HCV infection, but not for hepatitis B virus infection. Prospective studies about post-transfusional hepatitis C showed the risk of cirrhosis increases from 7.8 to 31.1 times if the patient consumed significant amounts of alcohol (> 80 g a day). One of the recommendations for every patient with HCV infection is to abstain from drinking alcohol.

  10. [A NEW PANDEMIC: ZIKA VIRUS INFECTION].

    PubMed

    Bourée, Patrice

    2016-06-01

    Zika virus is a flavivirus isolated in non human primates in 1647, then in humans 1954 (Uganda). It emerged on Micronesia (island af Yap) in 2007, then in French Polynesia in 2013-2014, in South America (mostly in Brazil and Colombia) in 2015 and in French West Indies in 2016. It is transmitted by the bite of Aedes mosquitoes. Zika virus infection is symptomatic in only 20% of cases and clinical presentation is associated with mild illness. But several neurological complications are reported (as Guillain-Barré syndrome: 48 cases in French Polynesia) and congenital malformations (microcephaly). Laboratory diagnosis is based on virus isolation by PCR. There is no specific treatment or vaccine available against the Zika virs. Prevention is based on measures of protection from mosquitoes bites.

  11. Human papilloma virus infection and psoriasis: Did human papilloma virus infection trigger psoriasis?

    PubMed Central

    Jain, Sonia P.; Gulhane, Sachin; Pandey, Neha; Bisne, Esha

    2015-01-01

    Psoriasis is an autoimmune chronic inflammatory skin disease known to be triggered by streptococcal and HIV infections. However, human papilloma virus infection (HPV) as a triggering factor for the development of psoriasis has not been reported yet. We, hereby report a case of plaque type with inverse psoriasis which probably could have been triggered by genital warts (HPV infection) and discuss the possible pathomechanisms for their coexistence and its management. PMID:26692619

  12. Prevalence of Hepatitis Virus Infections in an Institution for Persons with Developmental Disabilities.

    ERIC Educational Resources Information Center

    Woodruff, Bradley A.; Vazquez, Elizabeth

    2002-01-01

    A study involving 1,235 residents of Sonoma Developmental Center found 3 residents had hepatitis C virus infections, and 633 had past or current hepatitis B virus infections. The prevalence of hepatitis B virus infection rose rapidly with longer residence in institutions. Hepatitis A virus infection had occurred in 494 residents. (Contains…

  13. Genetic and phenotypic properties of vero cell-adapted Japanese encephalitis virus SA14-14-2 vaccine strain variants and a recombinant clone, which demonstrates attenuation and immunogenicity in mice.

    PubMed

    Gromowski, Gregory D; Firestone, Cai-Yen; Bustos-Arriaga, José; Whitehead, Stephen S

    2015-01-01

    The live-attenuated Japanese encephalitis virus (JEV) SA14-14-2 vaccine, produced in primary hamster kidney cells, is safe and effective. Past attempts to adapt this virus to replicate in cells that are more favorable for vaccine production resulted in mutations that significantly reduced immunogenicity. In this study, 10 genetically distinct Vero cell-adapted JEV SA14-14-2 variants were isolated and a recombinant wild-type JEV clone, modified to contain the JEV SA14-14-2 polyprotein amino acid sequence, was recovered in Vero cells. A single capsid protein mutation (S66L) was important for Vero cell-adaptation. Mutations were also identified that modulated virus sensitivity to type I interferon-stimulation in Vero cells. A subset of JEV SA14-14-2 variants and the recombinant clone were evaluated in vivo and exhibited levels of attenuation that varied significantly in suckling mice, but were avirulent and highly immunogenic in weanling mice and are promising candidates for the development of a second-generation, recombinant vaccine.

  14. Immune-enhancing effect of nano-DNA vaccine encoding a gene of the prME protein of Japanese encephalitis virus and BALB/c mouse granulocyte-macrophage colony-stimulating factor

    PubMed Central

    ZHAI, YONGZHEN; ZHOU, YAN; LI, XIMEI; FENG, GUOHE

    2015-01-01

    Plasmid-encoded granulocyte-macrophage colony-stimulating factor (GM-CSF) is an adjuvant for genetic vaccines; however, how GM-CSF enhances immunogenicity remains to be elucidated. In the present study, it was demonstrated that injection of a plasmid encoding the premembrane (prM) and envelope (E) protein of Japanese encephalitis virus and mouse GM-CSF (pJME/GM-CSF) into mouse muscle recruited large and multifocal conglomerates of macrophages and granulocytes, predominantly neutrophils. During the peak of the infiltration, an appreciable number of immature dendritic cells (DCs) appeared, although no T and B-cells was detected. pJME/GM-CSF increased the number of splenic DCs and the expression of major histocompatibility complex class II (MHCII) on splenic DC, and enhanced the antigenic capture, processing and presentation functions of splenic DCs, and the cell-mediated immunity induced by the vaccine. These findings suggested that the immune-enhancing effect by pJME/GM-CSF was associated with infiltrate size and the appearance of integrin αx (CD11c)+cells. Chitosan-pJME/GM-CSF nanoparticles, prepared by coacervation via intramuscular injection, outperformed standard pJME/GM-CSF administrations in DC recruitment, antigen processing and presentation, and vaccine enhancement. This revealed that muscular injection of chitosan-pJME/GM-CSF nanoparticles may enhance the immunoadjuvant properties of GM-CSF. PMID:25738258

  15. Respiratory Syncytial Virus Infection (RSV): Transmission and Prevention

    MedlinePlus

    ... CDC Cancel Submit Search The CDC Respiratory Syncytial Virus Infection (RSV) Note: Javascript is disabled or is ... if you touch a surface that has the virus on it, like a doorknob, and then touch ...

  16. DIESEL EXHAUST ENHANCES INFLUENZA VIRUS INFECTIONS IN RESPIRATORY EPITHELIAL CELLS

    EPA Science Inventory

    Several factors, such as age and nutritional status can affect the susceptibility to influenza infections. Moreover, exposure to air pollutants, such as diesel exhaust (DE), has been shown to affect respiratory virus infections in rodent models. Influenza virus primarily infects ...

  17. The control of bovine viral diarrhoea virus infection.

    PubMed

    Harkness, J W

    1987-01-01

    In this paper, current ideas concerning the epidemiology of BVD virus infection are reviewed briefly, together with its possible economic implications. The different types of control strategies are considered. Problems associated with vaccination are discussed.

  18. Laboratory Evaluation of Infants with Possible Congenital Zika Virus Infection.

    PubMed

    Bell, Susan Givens

    2017-03-01

    Our understanding of the effects of maternal Zika virus infection on the newborn continues to evolve. First discovered in 1947 in the Zika Forest in Uganda, the world became more aware of the virus in 2015, with reports of hundreds of cases of microcephaly in Brazilian newborns whose mothers reported symptoms related to Zika viral infection during pregnancy. This article reviews the current guidelines for laboratory evaluation of newborns with possible congenital Zika virus infection.

  19. Hepatitis C virus infection after renal transplantation.

    PubMed

    Romero, E; Galindo, P; Bravo, J A; Osorio, J M; Pérez, A; Baca, Y; Ferreira, C; Asensio, C; Osuna, A

    2008-11-01

    Hepatitis C virus (HCV) infection is the main cause of liver disease after renal transplantation. Most patients have seroconverted on dialysis to positive RNA. The viral load increases during immunosuppressive therapy. The risk of developing chronic liver disease is related to the histopathologic findings, duration and severity of the disease, immunosuppression, and transplantation time. Hepatitis C virus infection can predict onset, of proteinuria and diabetes. We studied 868 patients who received renal transplants between (1987 and 2006), of whom 18.7% were seropositive for HCV. We observed a higher rate of HCV-seropositive patients related to the duration of hemodialysis therapy. Of the HCV seropositive patients, 77% had received renal allografts before 1998. There was no difference between the sexes; however, the HCV positive patients were younger. Polymerase chain reaction tests results were positive in 91.6% of the patients with HCV antibodies. The prevalence of diabetes was greater among HCV positive patients, as was as the persistence of proteinuria. Cryoglobulins were positive in 30.8%. The incidence of acute rejection episodes in the first year was similar between groups. Of the HCV-positive patients, 80.2% were treated with cyclosporine, most patients continued this therapy throughout the study. We observed no significant difference in mortality end graft survival rate between the two groups. However, renal function differed significantly at some points during the evolution of the clinical course. Renal transplantation is still the best treatment option in patients with chronic renal disease.

  20. Management of hepatitis B virus infection.

    PubMed

    Lee, Haeok; Park, Wanju; Yang, Jin Hyang; You, Kwang Soo

    2010-01-01

    An estimated 2 million people are living with chronic hepatitis B virus (CHBV) in the United States and are at risk for long-term consequences such as cirrhosis, liver decompensation, and hepatocellular carcinoma. Less than 10 years ago, there was no treatment of CHBV infection, but now, new drugs have recently been approved and there is considerable new knowledge about the treatment of CHBV infection. Recently, consensus guidelines for the management of hepatitis B virus infection have been released by the National Institutes of Health and the American Medical Association, addressing the selection of patients and drugs for treatments. Determining what constitutes best practices to manage patients with CHBV is challenging and requires nurses and nurse practitioners to acquire and maintain up-to-date knowledge to understand recently approved drugs and disease management. Nurses and nurse practitioners should know how to identify patients who need treatment and how to educate, counsel, and monitor treatment adherence and side effects; these skills are crucially important. The goal of this article is to provide nurses with the most current consensus guidelines for the management of CHBV infection and their application in nursing practice to optimize treatment to enhance patient outcomes.

  1. The neurobiology of varicella zoster virus infection

    PubMed Central

    Gilden, D.; Mahalingam, R.; Nagel, M. A.; Pugazhenthi, S.; Cohrs, R. J.

    2011-01-01

    Varicella zoster virus (VZV) is a neurotropic herpesvirus that infects nearly all humans. Primary infection usually causes chickenpox (varicella), after which virus becomes latent in cranial nerve ganglia, dorsal root ganglia and autonomic ganglia along the entire neuraxis. Although VZV cannot be isolated from human ganglia, nucleic acid hybridization and, later, polymerase chain reaction proved that VZV is latent in ganglia. Declining VZV-specific host immunity decades after primary infection allows virus to reactivate spontaneously, resulting in shingles (zoster) characterized by pain and rash restricted to 1-3 dermatomes. Multiple other serious neurological and ocular disorders also result from VZV reactivation. This review summarizes the current state of knowledge of the clinical and pathological complications of neurological and ocular disease produced by VZV reactivation, molecular aspects of VZV latency, VZV virology and VZV-specific immunity, the role of apoptosis in VZV-induced cell death, and the development of an animal model provided by simian varicella virus infection of monkeys. PMID:21342215

  2. Myeloradiculopathy associated with chikungunya virus infection.

    PubMed

    Bank, Anna M; Batra, Ayush; Colorado, Rene A; Lyons, Jennifer L

    2016-02-01

    Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that is endemic to parts of Africa, South and Southeast Asia, and more recently the Caribbean. Patients typically present with fever, rash, and arthralgias, though neurologic symptoms, primarily encephalitis, have been described. We report the case of a 47-year-old woman who was clinically diagnosed with CHIKV while traveling in the Dominican Republic and presented 10 days later with left lower extremity weakness, a corresponding enhancing thoracic spinal cord lesion, and positive CHIKV serologies. She initially responded to corticosteroids, followed by relapsing symptoms and gradual clinical improvement. The time lapse between acute CHIKV infection and the onset of myelopathic sequelae suggests an immune-mediated phenomenon rather than direct activity of the virus itself. Chikungunya virus should be considered in the differential diagnosis of myelopathy in endemic areas. The progression of symptoms despite corticosteroid administration suggests more aggressive immunomodulatory therapies may be warranted at disease onset.

  3. Pathogenesis of human immunodeficiency virus infection.

    PubMed Central

    Levy, J A

    1993-01-01

    The lentivirus human immunodeficiency virus (HIV) causes AIDS by interacting with a large number of different cells in the body and escaping the host immune response against it. HIV is transmitted primarily through blood and genital fluids and to newborn infants from infected mothers. The steps occurring in infection involve an interaction of HIV not only with the CD4 molecule on cells but also with other cellular receptors recently identified. Virus-cell fusion and HIV entry subsequently take place. Following virus infection, a variety of intracellular mechanisms determine the relative expression of viral regulatory and accessory genes leading to productive or latent infection. With CD4+ lymphocytes, HIV replication can cause syncytium formation and cell death; with other cells, such as macrophages, persistent infection can occur, creating reservoirs for the virus in many cells and tissues. HIV strains are highly heterogeneous, and certain biologic and serologic properties determined by specific genetic sequences can be linked to pathogenic pathways and resistance to the immune response. The host reaction against HIV, through neutralizing antibodies and particularly through strong cellular immune responses, can keep the virus suppressed for many years. Long-term survival appears to involve infection with a relatively low-virulence strain that remains sensitive to the immune response, particularly to control by CD8+ cell antiviral activity. Several therapeutic approaches have been attempted, and others are under investigation. Vaccine development has provided some encouraging results, but the observations indicate the major challenge of preventing infection by HIV. Ongoing research is necessary to find a solution to this devastating worldwide epidemic. Images PMID:8464405

  4. Cell-mediated immune responses in healthy children with a history of subclinical infection with Japanese encephalitis virus: analysis of CD4+ and CD8+ T cell target specificities by intracellular delivery of viral proteins using the human immunodeficiency virus Tat protein transduction domain.

    PubMed

    Kumar, Priti; Krishna, Venkatramana D; Sulochana, Paramadevanapalli; Nirmala, Gejjehalli; Haridattatreya, Maganti; Satchidanandam, Vijaya

    2004-02-01

    Japanese encephalitis virus (JEV), a single-stranded positive-sense RNA virus of the family Flaviviridae, is the major cause of paediatric encephalitis in Asia. The high incidence of subclinical infections in Japanese encephalitis-endemic areas and subsequent evasion of encephalitis points to the development of immune responses against JEV. Humoral responses play a central role in protection against JEV; however, cell-mediated immune responses contributing to this end are not fully understood. The structural envelope (E) protein, the major inducer of neutralizing antibodies, is a poor target for T cells in natural JEV infections. The extent to which JEV non-structural proteins are targeted by T cells in subclinically infected healthy children would help to elucidate the role of cell-mediated immunity in protection against JEV as well as other flaviviral infections. The property of the Tat peptide of Human immunodeficiency virus to transduce proteins across cell membranes, facilitating intracellular protein delivery following exogenous addition to cultured cells, prompted us to express the four largest proteins of JEV, comprising 71 % of the JEV genome coding sequence, as Tat fusions for enumerating the frequencies of virus-specific CD4(+) and CD8(+) T cells in JEV-immune donors. At least two epitopes recognized by distinct HLA alleles were found on each of the non-structural proteins, with dominant antiviral Th1 T cell responses to the NS3 protein in nearly 96 % of the cohort. The data presented here show that non-structural proteins are frequently targeted by T cells in natural JEV infections and may be efficacious supplements for the predominantly antibody-eliciting E-based JEV vaccines.

  5. Entacapone, a catechol-O-methyltransferase inhibitor, improves the motor activity and dopamine content of basal ganglia in a rat model of Parkinson's disease induced by Japanese encephalitis virus.

    PubMed

    Hamaue, Naoya; Ogata, Akihiko; Terado, Mutsuko; Tsuchida, Shirou; Yabe, Ichiro; Sasaki, Hidenao; Hirafuji, Masahiko; Togashi, Hiroko; Aoki, Takashi

    2010-01-14

    Levodopa is the main medication used for the treatment of Parkinson's disease. However, dyskinesia and wearing-off appear after the administration of high-dose levodopa for a long period. To combat the dyskinesia and wearing-off, levodopa is used together with a dopamine (DA) receptor agonist, and the amount of levodopa is decreased. We have reported the monoamine oxidase (MAO)-B inhibitor selegiline to be effective for treating motor dysfunction in Parkinson's disease model rats. We analyzed the improvement in motor functions and catecholamine contents in various brain regions induced by a combination of the catechol-O-methyltransferase (COMT) inhibitor entacapone and a levodopa/dopadecarboxylase inhibitor (DDCI) in Japanese encephalitis virus (JEV) induced Parkinson's disease model rats. Entacapone (10 mg/kg) was administered via a single oral administration with levodopa/DDCI (10 mg/kg). The motor functions of the JEV model rats were significantly worsened, compared with those of the healthy control rats. The motor functions in the Parkinson's disease model rats were significantly recovered to the same levels as the healthy control rats by the combined administration of entacapone and levodopa/DDCI. A significant improvement in motor function was not demonstrated in the case of the administration of levodopa/DDCI alone. The striatal DA concentrations in the model rat brains were significantly increased by using levodopa/DDCI together with entacapone. Motor function was recovered by raising the striatum DA density in the model rats. Thus, COMT inhibitors are useful for decreasing the amount of levodopa administered to Parkinson's disease patients.

  6. Japanese encephalitis virus induces matrix metalloproteinase-9 expression via a ROS/c-Src/PDGFR/PI3K/Akt/MAPKs-dependent AP-1 pathway in rat brain astrocytes

    PubMed Central

    2012-01-01

    Background Japanese encephalitis virus (JEV) infection is a major cause of acute encephalopathy in children, which destroys central nervous system (CNS) cells, including astrocytes and neurons. Matrix metalloproteinase (MMP)-9 has been shown to degrade components of the basal lamina, leading to disruption of the blood-brain barrier (BBB) and to contribute to neuroinflammatory responses in many neurological diseases. However, the detailed mechanisms of JEV-induced MMP-9 expression in rat brain astrocytes (RBA-1 cells) are largely unclear. Methods In this study, the effect of JEV on expression of MMP-9 was determined by gelatin zymography, western blot analysis, RT-PCR, and promoter assay. The involvement of AP-1 (c-Jun and c-Fos), c-Src, PDGFR, PI3K/Akt, and MAPKs in these responses were investigated by using the selective pharmacological inhibitors and transfection with siRNAs. Results Here, we demonstrate that JEV induces expression of pro-form MMP-9 via ROS/c-Src/PDGFR/PI3K/Akt/MAPKs-dependent, AP-1 activation in RBA-1 cells. JEV-induced MMP-9 expression and promoter activity were inhibited by pretreatment with inhibitors of AP-1 (tanshinone), c-Src (PP1), PDGFR (AG1296), and PI3K (LY294002), and by transfection with siRNAs of c-Jun, c-Fos, PDGFR, and Akt. Moreover, JEV-stimulated AP-1 activation was inhibited by pretreatment with the inhibitors of c-Src, PDGFR, PI3K, and MAPKs. Conclusion From these results, we conclude that JEV activates the ROS/c-Src/PDGFR/PI3K/Akt/MAPKs pathway, which in turn triggers AP-1 activation and ultimately induces MMP-9 expression in RBA-1 cells. These findings concerning JEV-induced MMP-9 expression in RBA-1 cells imply that JEV might play an important role in CNS inflammation and diseases. PMID:22251375

  7. A randomized study of the immunogenicity and safety of Japanese encephalitis chimeric virus vaccine (JE-CV) in comparison with SA14-14-2 vaccine in children in the Republic of Korea.

    PubMed

    Kim, Dong Soo; Houillon, Guy; Jang, Gwang Cheon; Cha, Sung-Ho; Choi, Soo-Han; Lee, Jin; Kim, Hwang Min; Kim, Ji Hong; Kang, Jin Han; Kim, Jong-Hyun; Kim, Ki Hwan; Kim, Hee Soo; Bang, Joon; Naimi, Zulaikha; Bosch-Castells, Valérie; Boaz, Mark; Bouckenooghe, Alain

    2014-01-01

    A new live attenuated Japanese encephalitis chimeric virus vaccine (JE-CV) has been developed based on innovative technology to give protection against JE with an improved immunogenicity and safety profile. In this phase 3, observer-blind study, 274 children aged 12-24 months were randomized 1:1 to receive one dose of JE-CV (Group JE-CV) or the SA14-14-2 vaccine currently used to vaccinate against JE in the Republic of Korea (Group SA14-14-2). JE neutralizing antibody titers were assessed using PRNT50 before and 28 days after vaccination. The primary endpoint of non-inferiority of seroconversion rates on D28 was demonstrated in the Per Protocol analysis set as the difference between Group JE-CV and Group SA14-14-2 was 0.9 percentage points (95% confidence interval [CI]: -2.35; 4.68), which was above the required -10%. Seroconversion and seroprotection rates 28 days after administration of a single vaccine dose were 100% in Group JE-CV and 99.1% in Group SA14-14-2; all children except one (Group SA14-14-2) were seroprotected. Geometric mean titers (GMTs) increased in both groups from D0 to D28; GM of titer ratios were slightly higher in Group JE-CV (182 [95% CI: 131; 251]) than Group SA14-14-2 (116 [95% CI: 85.5, 157]). A single dose of JE-CV was well tolerated and no safety concerns were identified. In conclusion, a single dose of JE-CV or SA14-14-2 vaccine elicited a comparable immune response with a good safety profile. Results obtained in healthy Korean children aged 12-24 months vaccinated with JE-CV are consistent with those obtained in previous studies conducted with JE-CV in toddlers.

  8. Avian influenza virus infections in humans.

    PubMed

    Wong, Samson S Y; Yuen, Kwok-Yung

    2006-01-01

    Seroepidemiologic and virologic studies since 1889 suggested that human influenza pandemics were caused by H1, H2, and H3 subtypes of influenza A viruses. If not for the 1997 avian A/H5N1 outbreak in Hong Kong of China, subtype H2 is the likely candidate for the next pandemic. However, unlike previous poultry outbreaks of highly pathogenic avian influenza due to H5 that were controlled by depopulation with or without vaccination, the presently circulating A/H5N1 genotype Z virus has since been spreading from Southern China to other parts of the world. Migratory birds and, less likely, bird trafficking are believed to be globalizing the avian influenza A/H5N1 epidemic in poultry. More than 200 human cases of avian influenza virus infection due to A/H5, A/H7, and A/H9 subtypes mainly as a result of poultry-to-human transmission have been reported with a > 50% case fatality rate for A/H5N1 infections. A mutant or reassortant virus capable of efficient human-to-human transmission could trigger another influenza pandemic. The recent isolation of this virus in extrapulmonary sites of human diseases suggests that the high fatality of this infection may be more than just the result of a cytokine storm triggered by the pulmonary disease. The emergence of resistance to adamantanes (amantadine and rimantadine) and recently oseltamivir while H5N1 vaccines are still at the developmental stage of phase I clinical trial are causes for grave concern. Moreover, the to-be pandemic strain may have little cross immunogenicity to the presently tested vaccine strain. The relative importance and usefulness of airborne, droplet, or contact precautions in infection control are still uncertain. Laboratory-acquired avian influenza H7N7 has been reported, and the laboratory strains of human influenza H2N2 could also be the cause of another pandemic. The control of this impending disaster requires more research in addition to national and international preparedness at various levels. The

  9. Paradoxical role of antibodies in dengue virus infections: considerations for prophylactic vaccine development.

    PubMed

    Acosta, Eliana G; Bartenschlager, Ralf

    2016-01-01

    Highly effective prophylactic vaccines for flaviviruses including yellow fever virus, tick-borne encephalitis virus and Japanese encephalitis virus are currently in use. However, the development of a dengue virus (DENV) vaccine has been hampered by the requirement of simultaneous protection against four distinct serotypes and the threat that DENV-specific antibodies might either mediate neutralization or, on the contrary, exacerbate disease through the phenomenon of antibody-dependent enhancement (ADE) of infection. Therefore, understanding the cellular, biochemical and molecular basis of antibody-mediated neutralization and ADE are fundamental for the development of a safe DENV vaccine. Here we summarize current structural and mechanistic knowledge underlying these phenomena. We also review recent results demonstrating that the humoral immune response triggered during natural DENV infection is able to generate neutralizing antibodies binding complex quaternary epitopes only present on the surface of intact virions.

  10. Peptide inhibitors against herpes simplex virus infections.

    PubMed

    Galdiero, Stefania; Falanga, Annarita; Tarallo, Rossella; Russo, Luigi; Galdiero, Emilia; Cantisani, Marco; Morelli, Giancarlo; Galdiero, Massimiliano

    2013-03-01

    Herpes simplex virus (HSV) is a significant human pathogen causing mucocutaneous lesions primarily in the oral or genital mucosa. Although acyclovir (ACV) and related nucleoside analogs provide successful treatment, HSV remains highly prevalent worldwide and is a major cofactor for the spread of human immunodeficiency virus. Encephalitis, meningitis, and blinding keratitis are among the most severe diseases caused by HSV. ACV resistance poses an important problem for immunocompromised patients and highlights the need for new safe and effective agents; therefore, the development of novel strategies to eradicate HSV is a global public health priority. Despite the continued global epidemic of HSV and extensive research, there have been few major breakthroughs in the treatment or prevention of the virus since the introduction of ACV in the 1980s. A therapeutic strategy at the moment not fully addressed is the use of small peptide molecules. These can be either modeled on viral proteins or derived from antimicrobial peptides. Any peptide that interrupts protein-protein or viral protein-host cell membrane interactions is potentially a novel antiviral drug and may be a useful tool for elucidating the mechanisms of viral entry. This review summarizes current knowledge and strategies in the development of synthetic and natural peptides to inhibit HSV infectivity.

  11. Magnetic resonance imaging findings in acute canine distemper virus infection.

    PubMed

    Bathen-Noethen, A; Stein, V M; Puff, C; Baumgaertner, W; Tipold, A

    2008-09-01

    Demyelination is the prominent histopathological hallmark in the acute stage of canine distemper virus infection. Magnetic resonance imaging is an important diagnostic tool in human beings to determine demyelination in the brain, for example in multiple sclerosis. Five young dogs with clinically suspected canine distemper virus infection were subjected to magnetic resonance imaging of the brain and histopathological and immunohistochemical examinations. Hyperintense lesions and loss of contrast between grey and white matter were detected in T2-weighted images in the cerebellum and/or in the brainstem of three dogs, which correlated with demyelination demonstrated in histopathological examination. Furthermore, increased signal intensities in T2-weighted images were seen in the temporal lobe of four dogs with no evidence of demyelination. Magnetic resonance imaging seems to be a sensitive tool for the visualisation of in vivo myelination defects in dogs with acute canine distemper virus infection. Postictal oedema and accumulation of antigen positive cells have to be considered an important differential diagnosis.

  12. First Imported Case of Zika Virus Infection into Korea.

    PubMed

    Jang, Hee-Chang; Park, Wan Beom; Kim, Uh Jin; Chun, June Young; Choi, Su-Jin; Choe, Pyoeng Gyun; Jung, Sook-In; Jee, Youngmee; Kim, Nam-Joong; Choi, Eun Hwa; Oh, Myoung-Don

    2016-07-01

    Since Zika virus has been spreading rapidly in the Americas from 2015, the outbreak of Zika virus infection becomes a global health emergency because it can cause neurological complications and adverse fetal outcome including microcephaly. Here, we report clinical manifestations and virus isolation findings from a case of Zika virus infection imported from Brazil. The patient, 43-year-old Korean man, developed fever, myalgia, eyeball pain, and maculopapular rash, but not neurological manifestations. Zika virus was isolated from his semen, and reverse-transcriptase PCR was positive for the virus in the blood, urine, and saliva on the 7th day of the illness but was negative on the 21st day. He recovered spontaneously without any neurological complications. He is the first case of Zika virus infection in Korea imported from Brazil.

  13. Natural killer cells in hepatitis B virus infection.

    PubMed

    Wu, Shao-fei; Wang, Wen-jing; Gao, Yue-qiu

    2015-01-01

    Natural killer cells are a unique type of lymphocytes with cytotoxic capacity, and play important roles against tumors and infections. Recently, natural killer cells have been increasingly valued in their effects in hepatitis B virus infection. Since hepatitis B virus is not cytopathic, the subsequent antiviral immune responses of the host are responsible for sustaining the liver injury, which may result in cirrhosis and even hepatocellular carcinoma. Many studies have confirmed that natural killer cells participate in anti-hepatitis B virus responses both in the early phase after infection and in the chronic phase via cytolysis, degranulation, and cytokine secretion. However, natural killer cells play dichotomic roles: they exert antiviral and immunoregulatory functions whilst contribute to the pathogenesis of liver injury. Here, we review the roles of natural killer cells in hepatitis B virus infection, introducing novel therapeutic strategies for controlling hepatitis B virus infection via the modulation of natural killer cells.

  14. Fetal Magnetic Resonance Imaging Findings in Prenatal Zika Virus Infection.

    PubMed

    Sanín-Blair, José Enrique; Gutiérrez-Márquez, Carolina; Herrera, Diego A; Vossough, Arastoo

    2017-03-14

    Brain lesions and malformations have been described on ultrasonography of prenatal Zika infection; however, there are scarce reports about fetal magnetic resonance (MR) findings. We report 3 cases of fetuses with confirmed intrauterine Zika virus infection evaluated by ultrasound and fetal MR. Various morphometric measurements were assessed and brain maturation was calculated with the fetal total maturation score. Fetuses with prenatal Zika virus infection showed retardation in brain maturation indexes evaluated by fetal MR. Brain calcifications were demonstrated by neurosonography in all cases, while fetal MR characterized the specific type of cortical development malformation.

  15. Hepatitis C Virus Infection: Looking for Interferon Free Regimens

    PubMed Central

    González-Moreno, J.; Payeras-Cifre, A.

    2013-01-01

    Recent developments of new drugs' combinations are changing the treatment paradigm in hepatitis C virus infection. Due to the side effect profile of pegylated interferons, interferon-sparing regimens have become the main target in chronic hepatitis C treatment research. Recent proofs of concept studies have suggested that cure of chronic hepatitis C can be achieved without interferon. The purpose of this paper is to provide an overview of the clinical results recently reported for the treatment of hepatitis C virus infection with interferon-free regimens, focusing on the most promising new compounds and combinations. PMID:23710151

  16. Human Jamestown canyon virus infection --- Montana, 2009.

    PubMed

    2011-05-27

    Jamestown Canyon virus (JCV) is a mosquito-borne zoonotic pathogen belonging to the California serogroup of bunyaviruses. Although JCV is widely distributed throughout temperate North America, reports of human JCV infection in the United States are rare. This is the first report of human JCV infection detected in Montana, one of only 15 cases reported in the United States since 2004, when JCV became reportable. On May 26, 2009, a man aged 51 years with no travel history outside of Montana went to a local emergency department immediately following onset of fever, severe frontal headache, dizziness, left-sided numbness, and tingling. His blood pressure was elevated. Stroke was ruled out, oxygen was administered, medication was prescribed for hypertension, and the patient was sent home. One week later, the patient visited his primary-care physician complaining of continued neurologic symptoms consistent with acute febrile encephalitis and recent mosquito bites. Although West Nile virus (WNV) disease was diagnosed based on detection of WNV-immunoglobulin M (IgM) and G (IgG) antibodies, subsequent testing indicated that the WNV antibodies were from a past infection and that his illness was caused by JCV. The final diagnosis of JCV infection was based on positive JCV-specific IgM enzyme-linked immunosorbent assay (ELISA) results and a fourfold rise in paired sample JCV plaque reduction neutralization test (PRNT) titers. This finding represents a previously unrecognized risk for JCV infection in Montana; clinicians should consider JCV infection when assessing patients for suspected arboviral infections.

  17. Autoimmune Encephalitis in Children

    PubMed Central

    Armangue, Thaís; Petit-Pedrol, Mar; Dalmau, Josep

    2013-01-01

    The causes of encephalitis are numerous, and extensive investigations for infectious agents and other etiologies are often negative. The discovery that many of these encephalitis are immune mediated has changed the approach to the diagnosis and treatment of these disorders. Moreover, the broad spectrum of symptoms including, psychosis, catatonia, alterations of behavior and memory, seizures, abnormal movements, and autonomic dysregulation usually requires a multidisciplinary treatment approach. This review focuses in several forms of encephalitis that occur in children, and for which an autoimmune etiology has been demonstrated (eg, anti-N-methyl-D-aspartate receptor encephalitis) or is strongly suspected (eg, Rasmussen encephalitis, limbic encephalitis, opsoclonus-myoclonus). The authors also review several disorders that may be immune mediated, such as the rapid onset obesity with hypothalamic dysfunction, hypoventilation and autonomic dysregulation (ROHHAD) syndrome and some encephalopathies with fever and status epilepticus. Recognition of novel immune-mediated encephalitis is important because some of these disorders are highly responsive to immunotherapy. PMID:22935553

  18. Increased Hospitalizations for Neuropathies as Indicators of Zika Virus Infection, according to Health Information System Data, Brazil

    PubMed Central

    Xavier, Diego Ricardo; Pavão, Ana Luiza; Boccolini, Cristiano Siqueira; Pina, Maria Fatima; Pedroso, Marcel; Romero, Dalia; Romão, Anselmo Rocha

    2016-01-01

    Evidence is increasing that Zika virus can cause extensive damage to the central nervous system, affecting both fetuses and adults. We sought to identify traces of possible clinical manifestations of nervous system diseases among the registers of hospital admissions recorded in the Brazilian Unified Health System. Time series of several diagnoses from the International Classification of Diseases, 10th Revision, were analyzed by using control diagrams, during January 2008–February 2016. Beginning in mid-2014, we observed an unprecedented and significant rise in the hospitalization rate for congenital malformations of the nervous system, Guillain-Barré syndrome, encephalitis, myelitis, and encephalomyelitis. These conditions are compatible with viral infection and inflammation-associated manifestations and may have been due to the entrance of Zika virus into Brazil. These findings show the necessity of adequately diagnosing and treating suspected cases of Zika virus infection and also that health surveillance systems can be improved by using routine data. PMID:27603576

  19. Screening for Hepatitis B Virus Infection in Nonpregnant Adolescents and Adults

    MedlinePlus

    ... Screening for Hepatitis B Virus Infection in Nonpregnant Adolescents and Adults The U.S. Preventive Services Task Force ( ... Screening for Hepatitis B Virus Infection in Nonpregnant Adolescents and Adults. This final recommendation statement applies only ...

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

    DTIC Science & Technology

    2000-01-01

    parents, Hank and Gail Schoneboom. They instilled in me a work ethic to be successful in any rigorous endeavor and nurtured the curiosity of the child...are the resident macrophages of the CNS, thought to arise from a common embryologic origin, the mesoderm (Cuadros and Navascues, 1998, Wozniak, 1998

  1. Experimental Zika virus infection induces spinal cord injury and encephalitis in newborn Swiss mice.

    PubMed

    Fernandes, Natália C C A; Nogueira, Juliana S; Réssio, Rodrigo A; Cirqueira, Cinthya S; Kimura, Lidia M; Fernandes, Karolina R; Cunha, Mariana S; Souza, Renato P; Guerra, Juliana M

    2017-02-01

    A widespread epidemic of Zika virus (ZIKV) infection was reported in 2015 in South and Central America, with neurological symptons including meningoencephalitis and Guillain-Barré syndrome in adults, besides an apparent increased incidence of microcephaly in infants born to infected mothers. It is becoming a necessity to have a trustworthy animal model to better understand ZIKV infection. In this study we used newborn white Swiss mice as a model to investigate the ZIKV strain recently isolated in Brazil. ZIKV was inoculated via intracerebral and subcutaneous routes and analysed through gross histopathology and immunohistochemistry. Here we demonstrated first that the intracerebral group (ICG) displayed severe cerebral lesions, with neuronal death, presence of apoptotic bodies, white matter degeneration and neutrophil perivascular cuffing. In the subcutaneous group (SCG), we observed moderate cerebral lesions, morphologically similar to that found in ICG and additional myelopathy, with architectural loss, marked by neuronal death and apoptotic bodies. Interestingly, we found an intense astrogliosis in brain of both groups, with increased immunoexpression of GFAP (glial fibrillary acidic protein) and presence of hypertrophic astrocytes. The spinal cord of subcutaneous group (SCG) exhibited reduction of astrocytes, but those positive for GFAP were hypertrophic and presented prolonged cellular processes. Finally significant lesions in the central nervous system (CNS) were present in newborn mice inoculated by both routes, but SCG method led to an important neurological manifestations (including myelopathy), during a longer period of time and appears for us to be a better model for ZIKV infection.

  2. Atypical necrotizing encephalitis associated with systemic canine distemper virus infection in pups.

    PubMed

    Amude, Alexandre Mendes; Headley, Selwyn Arlington; Alfieri, Amauri Alcindo; Beloni, Suely Nunes Esteves; Alfieri, Alice Fernandes

    2011-12-01

    This report describes the naturally occurring atypical neuropathological manifestation of systemic canine distemper virus (CDV) infection in two 16-day-old Pit Bull pups. CDV-induced changes affected the gray and white matter of the forebrain while sparing the hindbrain. Histologically, there was necrosis with destruction of the nervous parenchyma due to an influx of inflammatory and reactive cells associated with eosinophilic intranuclear inclusion bodies within glial cells. Positive immunoreactivity against CDV antigens was predominantly observed within astrocytes and neurons. RT-PCR was used to amplify CDV-specific amplicons from brain fragments. These findings suggest the participation of CDV in the etiopathogenesis of these lesions.

  3. 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.

  4. 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

  5. Outbreak of West Nile Virus Infection in Greece, 2010

    PubMed Central

    Papa, Anna; Theocharopoulos, George; Dougas, Georgios; Athanasiou, Maria; Detsis, Marios; Baka, Agoritsa; Lytras, Theodoros; Mellou, Kassiani; Bonovas, Stefanos; Panagiotopoulos, Takis

    2011-01-01

    During 2010, an outbreak of West Nile virus infection occurred in Greece. A total of 197 patients with neuroinvasive disease were reported, of whom 33 (17%) died. Advanced age and a history of heart disease were independently associated with death, emphasizing the need for prevention of this infection in persons with these risk factors. PMID:22000357

  6. KINETIC PROFILE OF INFLUENZA VIRUS INFECTION IN THREE RAT STRAINS

    EPA Science Inventory

    Abstract

    Influenza infection is a respiratory disease of viral origin that can cause major epidemics in man. The influenza virus infects and damages epithelial cells of the respiratory tract and causes pneumonia. Lung lesions of mice infected with influenza virus resembl...

  7. Susceptibility of mouse macrophage J774 to dengue virus infection.

    PubMed

    Moreno-Altamirano, María M B; Sánchez-García, F Javier; Legorreta-Herrera, Martha; Aguilar-Carmona, Israel

    2007-01-01

    The aim of this study was to investigate whether the J774 mouse macrophage cell line could be used as an in vitro model for dengue virus infection (DENV). After 3 days, infection in J774 cells was assessed by detecting dengue virus non-structural protein 1 (NSP-1) production either by dot blot or indirect immunofluorescence assay (IFA) of saponine-permeabilized J774 cells and then confirmed by RT-PCR (171 bp product, corresponding to the DENV-2 core). Based on the presence of NSP-1 in infected but not in non-infected cells by both IFA and dot blot, as well as the amplification of a 171-bp DENV-2-specific RT-PCR product exclusively in the infected cells, the J774 cell line was found to be permissive for dengue virus infection. As far as we know, this is the first report that the J774 mouse macrophage cell line is infected with dengue virus and, thus, that it can be used as an alternative in vitro model for dengue virus infection studies. This finding could help to further elucidate the mechanisms involved in dengue virus infection and pathogenesis.

  8. Immune responses of patients to orf virus infection.

    PubMed

    Yirrell, D L; Vestey, J P; Norval, M

    1994-04-01

    Orf is a disease of sheep and goats which is caused by a parapox virus. It can be transmitted to humans, and is considered an occupational hazard by those handling sheep. In this paper we present the first report of both cell-mediated and humoral immune responses to naturally acquired orf virus infection in humans. Lymphoproliferative responses of peripheral blood mononuclear cells of patients to an orf virus antigen were vigorous soon after infection, but rapidly declined. Orf virus antibody levels, detected by ELISA, were shown to rise during infection. Western blot analysis confirmed this, and demonstrated that the antibody produced in response to the infection was directed against the 40-kDa viral surface tubule protein. Where direct comparisons were possible, the immune response of humans to orf virus infection was similar to that previously reported for sheep. Evidence was obtained suggesting that prior exposure to vaccinia virus (smallpox vaccination) provided no protection from subsequent orf virus infection. In addition, orf virus infection did not enhance immune responses to vaccinia virus antigens.

  9. The mortality of neonatal herpes simplex virus infection.

    PubMed

    Lopez-Medina, Eduardo; Cantey, Joseph B; Sánchez, Pablo J

    2015-06-01

    This retrospective study characterized the clinical course of 13 neonates who died with herpes simplex virus infection from 2001 to 2011, representing a 26% case-fatality rate. Fatal disease developed at ≤ 48 hours of age in one-third of infants, was mostly disseminated disease, and occurred despite early administration of high-dose acyclovir therapy.

  10. Genome-Wide Screening Uncovers the Significance of N-sulfation of Heparan Sulfate as a Host Cell Factor for Chikungunya Virus Infection.

    PubMed

    Tanaka, Atsushi; Tumkosit, Uranan; Nakamura, Shota; Motooka, Daisuke; Kishishita, Natsuko; Priengprom, Thongkoon; Sa-Ngasang, Areerat; Kinoshita, Taroh; Takeda, Naokazu; Maeda, Yusuke

    2017-04-12

    The molecular mechanisms underlying chikungunya virus (CHIKV) infection are poorly characterized. In this study, we analyzed the host factors involved in CHIKV infection using genome-wide screening. Human haploid HAP1 cells, into which an exon-trapping vector was introduced, were challenged with a vesicular stomatitis virus pseudotype bearing the CHIKV E3-E1 envelope proteins. Analysis of genes enriched in the cells resistant to the pseudotyped virus infection unveiled a critical role of N-sulfation of heparan sulfate (HS) for the infectivity of a clinically isolated CHIKV Thai #16856 strain to HAP1 cells. Knockout of NDST1 that catalyzes N-sulfation of HS greatly decreased the binding and infectivity of CHIKV Thai#16856 strain but not infectivity of Japanese encephalitis virus (JEV) and yellow fever virus (YFV). Whereas glycosaminoglycans were commonly required for efficient infectivity of CHIKV, JEV and YFV as shown by using B3GAT3 knockout cells, the tropism for N-sulfate was specific to CHIKV. Expression of chondroitin sulfate (CS) in NDST1-knockout HAP1 cells did not restore the binding of CHIKV Thai#16856 strain and the infectivity of its pseudotype but restored the infectivity of authentic CHIKV Thai#16856, suggesting that CS functions at the later steps after the CHIKV binding. Among the genes enriched in this screening, we found that TM9SF2 is critical for N-sulfation of HS and therefore for CHIKV infection, because it is involved in proper localization and stability of NDST1. Determination of the significance of and the relevant proteins to N-sulfation of HS may contribute to understanding mechanisms of CHIKV propagation, cell tropism and pathogenesis.IMPORTANCE Recent outbreaks of chikungunya fever have increased its clinical importance. Chikungunya virus (CHIKV) utilizes host glycosaminoglycans to bind efficiently to its target cells. However, the substructure in glycosaminoglycans required for CHIKV infection have not been characterized. Here, we

  11. Respiratory virus infection among hematopoietic cell transplant recipients: evidence for asymptomatic parainfluenza virus infection.

    PubMed

    Peck, Angela J; Englund, Janet A; Kuypers, Jane; Guthrie, Katherine A; Corey, Lawrence; Morrow, Rhoda; Hackman, Robert C; Cent, Anne; Boeckh, Michael

    2007-09-01

    The incidence of respiratory virus infection after hematopoietic cell transplantation (HCT) has probably been underestimated with conventional testing methods in symptomatic patients. This prospective study assessed viral infection episodes by testing weekly respiratory samples collected from HCT recipients, with and without symptoms reported by questionnaire, for 100 days after HCT. Samples were tested by culture and direct fluorescent antibody testing for respiratory syncytial virus (RSV), parainfluenza virus (PIV), and influenza A and B, and by quantitative reverse transcription-polymerase chain reaction for RSV, PIV, influenza A and B, and metapneumovirus (MPV). Of 122 patients, 30 (25%) had 32 infection episodes caused by RSV (5), PIV (17), MPV (6), influenza (3), RSV, or influenza (1). PIV, with a cumulative incidence estimate of 17.9%, was the only virus for which asymptomatic infection was detected. Lower virus copy number in patients with no or one symptom compared with 2 or more symptoms was found for all viruses in all patients (P < .001), with PIV infection having a similar virus-specific comparison (P = .004). Subclinical infection with PIV may help explain why infection-control programs that emphasize symptoms are effective against RSV and influenza but often not against PIV.

  12. Madariaga virus infection associated with a case of acute disseminated encephalomyelitis.

    PubMed

    Luciani, Kathia; Abadía, Iván; Martínez-Torres, Alex O; Cisneros, Julio; Guerra, Ilka; García, Mariana; Estripeaut, Dora; Carrera, Jean-Paul

    2015-06-01

    We present the first report of a pediatric case of acute disseminated encephalomyelitis (ADEM) associated with Madariaga virus infection (MADV, Alphavirus, Togaviridae; formerly known as South American variants of eastern equine encephalitis virus [EEEV]) in a patient of the 2010 alphaviral epidemic reported in Panama. The patient was admitted to the Hospital del Niño in Panama City with suspected meningitis, exhibited with decreased alertness and disorientation in space and time, hemiparesis, and left Babinski sign. The patient was transferred to the intensive care unit and treated with aciclovir and methylprednisolone. The magnetic resonance imaging (MRI) of the brain revealed multiple hyperintense lesions at T2-weighted images (T2) and fluid-attenuated inversion recovery (FLAIR) on the cortical-subcortical level. Sera samples obtained on days 6 and 12 were immunoglobulin M (IgM) positive for MADV. The findings on the clinical and cerebrospinal analyses, rapid symptom progression as well as neuroimaging, and serologic studies support our diagnosis. Our results suggest that MADV should be included in the etiologic differential diagnosis of ADEM in endemic countries.

  13. A randomized study of the immunogenicity and safety of Japanese Encephalitis Chimeric Virus Vaccine (JE-CV) in comparison with SA14-14-2 Vaccine in children in the Republic of Korea

    PubMed Central

    Kim, Dong Soo; Houillon, Guy; Jang, Gwang Cheon; Cha, Sung-Ho; Choi, Soo-Han; Lee, Jin; Kim, Hwang Min; Kim, Ji Hong; Kang, Jin Han; Kim, Jong-Hyun; Kim, Ki Hwan; Kim, Hee Soo; Bang, Joon; Naimi, Zulaikha; Bosch-Castells, Valérie; Boaz, Mark; Bouckenooghe, Alain

    2014-01-01

    A new live attenuated Japanese encephalitis chimeric virus vaccine (JE-CV) has been developed based on innovative technology to give protection against JE with an improved immunogenicity and safety profile. In this phase 3, observer-blind study, 274 children aged 12−24 months were randomized 1:1 to receive one dose of JE-CV (Group JE-CV) or the SA14–14–2 vaccine currently used to vaccinate against JE in the Republic of Korea (Group SA14–14–2). JE neutralizing antibody titers were assessed using PRNT50 before and 28 days after vaccination. The primary endpoint of non-inferiority of seroconversion rates on D28 was demonstrated in the Per Protocol analysis set as the difference between Group JE-CV and Group SA14–14–2 was 0.9 percentage points (95% confidence interval [CI]: −2.35; 4.68), which was above the required −10%. Seroconversion and seroprotection rates 28 days after administration of a single vaccine dose were 100% in Group JE-CV and 99.1% in Group SA14–14–2; all children except one (Group SA14–14–2) were seroprotected. Geometric mean titers (GMTs) increased in both groups from D0 to D28; GM of titer ratios were slightly higher in Group JE-CV (182 [95% CI: 131; 251]) than Group SA14–14–2 (116 [95% CI: 85.5, 157]). A single dose of JE-CV was well tolerated and no safety concerns were identified. In conclusion, a single dose of JE-CV or SA14–14–2 vaccine elicited a comparable immune response with a good safety profile. Results obtained in healthy Korean children aged 12−24 months vaccinated with JE-CV are consistent with those obtained in previous studies conducted with JE-CV in toddlers. PMID:25483480

  14. Profiling of Viral Proteins Expressed from the Genomic RNA of Japanese Encephalitis Virus Using a Panel of 15 Region-Specific Polyclonal Rabbit Antisera: Implications for Viral Gene Expression

    PubMed Central

    Yun, Sang-Im; Yun, Gil-Nam; Byun, Sung-June; Lee, Young-Min

    2015-01-01

    Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, is closely related to West Nile (WN), yellow fever (YF), and dengue (DEN) viruses. Its plus-strand genomic RNA carries a single open reading frame encoding a polyprotein that is cleaved into three structural (C, prM/M, and E) and at least seven nonstructural (NS1/NS1', NS2A, NS2B, NS3, NS4A, NS4B, and NS5) proteins, based on previous work with WNV, YFV, and DENV. Here, we aimed to profile experimentally all the viral proteins found in JEV-infected cells. We generated a collection of 15 JEV-specific polyclonal antisera covering all parts of the viral protein-coding regions, by immunizing rabbits with 14 bacterially expressed glutathione-S-transferase fusion proteins (for all nine viral proteins except NS2B) or with a chemically synthesized oligopeptide (for NS2B). In total lysates of JEV-infected BHK-21 cells, immunoblotting with these antisera revealed: (i) three mature structural proteins (~12-kDa C, ~8-kDa M, and ~53-kDa E), a precursor of M (~24-kDa prM) and three other M-related proteins (~10-14 kDa); (ii) the predicted ~45-kDa NS1 and its frameshift product, ~58-kDa NS1', with no evidence of the predicted ~25-kDa NS2A; (iii) the predicted but hardly detectable ~14-kDa NS2B and an unexpected but predominant ~12-kDa NS2B-related protein; (iv) the predicted ~69-kDa NS3 plus two major cleavage products (~34-kDa NS3N-term and ~35-kDa NS3C-term), together with at least nine minor proteins of ~16-52 kDa; (v) the predicted ~14-kDa NS4A; (vi) two NS4B-related proteins (~27-kDa NS4B and ~25-kDa NS4B'); and (vii) the predicted ~103-kDa NS5 plus at least three other NS5-related proteins (~15 kDa, ~27 kDa, and ~90 kDa). Combining these data with confocal microscopic imaging of the proteins’ intracellular localization, our study is the first to provide a solid foundation for the study of JEV gene expression, which is crucial for elucidating the regulatory mechanisms of JEV genome replication and pathobiology

  15. A Single N-Linked Glycosylation Site in the Japanese Encephalitis Virus prM Protein Is Critical for Cell Type-Specific prM Protein Biogenesis, Virus Particle Release, and Pathogenicity in Mice ▿ †

    PubMed Central

    Kim, Jeong-Min; Yun, Sang-Im; Song, Byung-Hak; Hahn, Youn-Soo; Lee, Chan-Hee; Oh, Hyun-Woo; Lee, Young-Min

    2008-01-01

    The prM protein of Japanese encephalitis virus (JEV) contains a single potential N-linked glycosylation site, N15-X16-T17, which is highly conserved among JEV strains and closely related flaviviruses. To investigate the role of this site in JEV replication and pathogenesis, we manipulated the RNA genome by using infectious JEV cDNA to generate three prM mutants (N15A, T17A, and N15A/T17A) with alanine substiting for N15 and/or T17 and one mutant with silent point mutations introduced into the nucleotide sequences corresponding to all three residues in the glycosylation site. An analysis of these mutants in the presence or absence of endoglycosidases confirmed the addition of oligosaccharides to this potential glycosylation site. The loss of prM N glycosylation, without significantly altering the intracellular levels of viral RNA and proteins, led to an ≈20-fold reduction in the production of extracellular virions, which had protein compositions and infectivities nearly identical to those of wild-type virions; this reduction occurred at the stage of virus release, rather than assembly. This release defect was correlated with small-plaque morphology and an N-glycosylation-dependent delay in viral growth. A more conservative mutation, N15Q, had the same effect as N15A. One of the four prM mutants, N15A/T17A, showed an additional defect in virus growth in mosquito C6/36 cells but not human neuroblastoma SH-SY5Y or hamster BHK-21 cells. This cell type dependence was attributed to abnormal N-glycosylation-independent biogenesis of prM. In mice, the elimination of prM N glycosylation resulted in a drastic decrease in virulence after peripheral inoculation. Overall, our findings indicate that this highly conserved N-glycosylation motif in prM is crucial for multiple stages of JEV biology: prM biogenesis, virus release, and pathogenesis. PMID:18524814

  16. A single N-linked glycosylation site in the Japanese encephalitis virus prM protein is critical for cell type-specific prM protein biogenesis, virus particle release, and pathogenicity in mice.

    PubMed

    Kim, Jeong-Min; Yun, Sang-Im; Song, Byung-Hak; Hahn, Youn-Soo; Lee, Chan-Hee; Oh, Hyun-Woo; Lee, Young-Min

    2008-08-01

    The prM protein of Japanese encephalitis virus (JEV) contains a single potential N-linked glycosylation site, N(15)-X(16)-T(17), which is highly conserved among JEV strains and closely related flaviviruses. To investigate the role of this site in JEV replication and pathogenesis, we manipulated the RNA genome by using infectious JEV cDNA to generate three prM mutants (N15A, T17A, and N15A/T17A) with alanine substituting for N(15) and/or T(17) and one mutant with silent point mutations introduced into the nucleotide sequences corresponding to all three residues in the glycosylation site. An analysis of these mutants in the presence or absence of endoglycosidases confirmed the addition of oligosaccharides to this potential glycosylation site. The loss of prM N glycosylation, without significantly altering the intracellular levels of viral RNA and proteins, led to an approximately 20-fold reduction in the production of extracellular virions, which had protein compositions and infectivities nearly identical to those of wild-type virions; this reduction occurred at the stage of virus release, rather than assembly. This release defect was correlated with small-plaque morphology and an N-glycosylation-dependent delay in viral growth. A more conservative mutation, N15Q, had the same effect as N15A. One of the four prM mutants, N15A/T17A, showed an additional defect in virus growth in mosquito C6/36 cells but not human neuroblastoma SH-SY5Y or hamster BHK-21 cells. This cell type dependence was attributed to abnormal N-glycosylation-independent biogenesis of prM. In mice, the elimination of prM N glycosylation resulted in a drastic decrease in virulence after peripheral inoculation. Overall, our findings indicate that this highly conserved N-glycosylation motif in prM is crucial for multiple stages of JEV biology: prM biogenesis, virus release, and pathogenesis.

  17. Histidine at residue 99 and the transmembrane region of the precursor membrane prM protein are important for the prM-E heterodimeric complex formation of Japanese encephalitis virus.

    PubMed

    Lin, Ying-Ju; Wu, Suh-Chin

    2005-07-01

    The formation of the flavivirus prM-E complex is an important step for the biogenesis of immature virions, which is followed by a subsequent cleavage of prM to M protein through cellular protease to result in the production and release of mature virions. In this study, the intracellular formation of the prM-E complex of Japanese encephalitis virus was investigated by baculovirus coexpression of prM and E in trans in Sf9 insect cells as analyzed by anti-E antibody immunoprecipitation and sucrose gradient sedimentation analysis. A series of carboxyl-terminally truncated prM mutant baculoviruses was constructed to demonstrate that the truncations of the transmembrane (TM) region resulted in a reduction of the formation of the stable prM-E complex by approximately 40% for the TM1 (at residues 130 to 147 [prM130-147]) truncation and 20% for TM2 (at prM153-167) truncation. Alanine-scanning site-directed mutagenesis on the prM99-103 region indicated that the His99 residue was the critical prM binding element for stable prM-E heterodimeric complex formation. The single amino acid mutation at the His99 residue of prM abolishing the prM-E interaction was not due to reduced expression or different subcellular location of the mutant prM protein involved in prM-E interactions as characterized by pulse-chase labeling and confocal scanning microscopic analysis. Recombinant subviral particles were detected in the Sf9 cell culture supernatants by baculovirus coexpression of prM and E proteins but not with the prM H99A mutant. Sequence alignment analysis was further conducted with different groups of flaviviruses to show that the prM H99 residues are generally conserved. Our findings are the first report to characterize the minimum binding elements of the prM protein that are involved in prM-E interactions of flaviviruses. This information, concerning a molecular framework for the prM protein, is considered to elucidate the structure/function relationship of the prM-E complex

  18. Managing patients with encephalitis.

    PubMed

    Matata, Claire; Easton, Ava; Michael, Benedict; Evans, Becky; Ward, Deborah; Solomon, Tom; Kneen, Rachel

    2015-11-11

    This article provides an overview of encephalitis and addresses its diagnosis, some of the common presenting signs and symptoms, and the different aspects of nursing care required for these patients. In particular, it addresses how to explain encephalitis to the patient's relatives, the rehabilitation needs of these patients, and important aspects of discharge planning. Tests that are necessary for diagnosis in patients with suspected encephalitis and the importance of these are explained.

  19. First case of imported Zika virus infection in Spain.

    PubMed

    Bachiller-Luque, Pablo; Domínguez-Gil González, Marta; Álvarez-Manzanares, Jesús; Vázquez, Ana; De Ory, Fernando; Sánchez-Seco Fariñas, M Paz

    2016-04-01

    We report a case of Zika virus (ZIKV) infection in a patient with diarrhea, fever, synovitis, non-purulent conjunctivitis, and with discreet retro-orbital pain, after returning from Colombia in January 2016. The patient referred several mosquito bites. Presence of ZIKV was detected by PCR (polymerase chain reaction) in plasma. Rapid microbiological diagnosis of ZIKV infection is needed in European countries with circulation of its vector, in order to avoid autochthonous circulation. The recent association of ZIKV infection with abortion and microcephaly, and a Guillain-Barré syndrome highlights the need for laboratory differentiation of ZIKV from other virus infection. Women with potential risk for Zika virus infection who are pregnant or planning to become pregnant must mention that fact during prenatal visits in order to be evaluated and properly monitored.

  20. Biology of Zika Virus Infection in Human Skin Cells

    PubMed Central

    Hamel, Rodolphe; Dejarnac, Ophélie; Wichit, Sineewanlaya; Ekchariyawat, Peeraya; Neyret, Aymeric; Luplertlop, Natthanej; Perera-Lecoin, Manuel; Surasombatpattana, Pornapat; Talignani, Loïc; Thomas, Frédéric; Cao-Lormeau, Van-Mai; Choumet, Valérie; Briant, Laurence; Desprès, Philippe; Amara, Ali; Yssel, Hans

    2015-01-01

    ABSTRACT Zika virus (ZIKV) is an emerging arbovirus of the Flaviviridae family, which includes dengue, West Nile, yellow fever, and Japanese encephalitis viruses, that causes a mosquito-borne disease transmitted by the Aedes genus, with recent outbreaks in the South Pacific. Here we examine the importance of human skin in the entry of ZIKV and its contribution to the induction of antiviral immune responses. We show that human dermal fibroblasts, epidermal keratinocytes, and immature dendritic cells are permissive to the most recent ZIKV isolate, responsible for the epidemic in French Polynesia. Several entry and/or adhesion factors, including DC-SIGN, AXL, Tyro3, and, to a lesser extent, TIM-1, permitted ZIKV entry, with a major role for the TAM receptor AXL. The ZIKV permissiveness of human skin fibroblasts was confirmed by the use of a neutralizing antibody and specific RNA silencing. ZIKV induced the transcription of Toll-like receptor 3 (TLR3), RIG-I, and MDA5, as well as several interferon-stimulated genes, including OAS2, ISG15, and MX1, characterized by strongly enhanced beta interferon gene expression. ZIKV was found to be sensitive to the antiviral effects of both type I and type II interferons. Finally, infection of skin fibroblasts resulted in the formation of autophagosomes, whose presence was associated with enhanced viral replication, as shown by the use of Torin 1, a chemical inducer of autophagy, and the specific autophagy inhibitor 3-methyladenine. The results presented herein permit us to gain further insight into the biology of ZIKV and to devise strategies aiming to interfere with the pathology caused by this emerging flavivirus. IMPORTANCE Zika virus (ZIKV) is an arbovirus belonging to the Flaviviridae family. Vector-mediated transmission of ZIKV is initiated when a blood-feeding female Aedes mosquito injects the virus into the skin of its mammalian host, followed by infection of permissive cells via specific receptors. Indeed, skin immune

  1. Pathology of Lassa Virus Infection in the Rhesus Monkey

    DTIC Science & Technology

    1982-01-01

    examined. Lassa fever ’- is an infectious, febrile disease nuclear cell infiltrates and mucosal hemorrhages. of man caused by Lassa virus (LASV), a member... virus titers, suggests that virus replication 1. Buckley, S. M., and Casals, J., 1973. Lassa fever , in the kidney parenchyma was unlikely. A few a new...A., 1973. Comparative pathology of phology and morphogenesis of arenaviruses . BDg. Lassa virus infection in monkeys, guinea pip, W.H.O., 52: 409-419

  2. Electron microscope evidence of virus infection in cultured marine fish

    NASA Astrophysics Data System (ADS)

    Sun, Xiu-Qin; Zhang, Jin-Xing; Qu, Ling-Yun

    2000-09-01

    Electron microscope investigation on the red sea bream ( Pagrosomus major), bastard halibut ( Paralichthys olivaceus) and stone flounder ( Kareius bicoloratus) in North China revealed virus infection in the bodies of the dead and diseased fish. These viruses included the lymphocystis disease virus (LDV), parvovirus, globular virus, and a kind of baculavirus which was not discovered and reported before and is now tentatively named baculavirus of stone flounder ( Kareius bicoloratus).

  3. Protective effect of dietary xylitol on influenza A virus infection.

    PubMed

    Yin, Sun Young; Kim, Hyoung Jin; Kim, Hong-Jin

    2014-01-01

    Xylitol has been used as a substitute for sugar to prevent cavity-causing bacteria, and most studies have focused on its benefits in dental care. Meanwhile, the constituents of red ginseng (RG) are known to be effective in ameliorating the symptoms of influenza virus infection when they are administered orally for 14 days. In this study, we investigated the effect of dietary xylitol on influenza A virus infection (H1N1). We designed regimens containing various fractions of RG (RGs: whole extract, water soluble fraction, saponin and polysaccharide) and xylitol, and combination of xylitol with the RG fractions. Mice received the various combinations orally for 5 days prior to lethal influenza A virus infection. Almost all the mice died post challenge when xylitol or RGs were administered separately. Survival was markedly enhanced when xylitol was administered along with RGs, pointing to a synergistic effect. The effect of xylitol plus RG fractions increased with increasing dose of xylitol. Moreover, dietary xylitol along with the RG water soluble fraction significantly reduced lung virus titers after infection. Therefore, we suggest that dietary xylitol is effective in ameliorating influenza-induced symptoms when it is administered with RG fractions, and this protective effect of xylitol should be considered in relation to other diseases.

  4. Protective Effect of Dietary Xylitol on Influenza A Virus Infection

    PubMed Central

    Yin, Sun Young; Kim, Hyoung Jin; Kim, Hong-Jin

    2014-01-01

    Xylitol has been used as a substitute for sugar to prevent cavity-causing bacteria, and most studies have focused on its benefits in dental care. Meanwhile, the constituents of red ginseng (RG) are known to be effective in ameliorating the symptoms of influenza virus infection when they are administered orally for 14 days. In this study, we investigated the effect of dietary xylitol on influenza A virus infection (H1N1). We designed regimens containing various fractions of RG (RGs: whole extract, water soluble fraction, saponin and polysaccharide) and xylitol, and combination of xylitol with the RG fractions. Mice received the various combinations orally for 5 days prior to lethal influenza A virus infection. Almost all the mice died post challenge when xylitol or RGs were administered separately. Survival was markedly enhanced when xylitol was administered along with RGs, pointing to a synergistic effect. The effect of xylitol plus RG fractions increased with increasing dose of xylitol. Moreover, dietary xylitol along with the RG water soluble fraction significantly reduced lung virus titers after infection. Therefore, we suggest that dietary xylitol is effective in ameliorating influenza-induced symptoms when it is administered with RG fractions, and this protective effect of xylitol should be considered in relation to other diseases. PMID:24392148

  5. Potent neutralizing monoclonal antibodies against Ebola virus infection

    PubMed Central

    Zhang, Qi; Gui, Miao; Niu, Xuefeng; He, Shihua; Wang, Ruoke; Feng, Yupeng; Kroeker, Andrea; Zuo, Yanan; Wang, Hua; Wang, Ying; Li, Jiade; Li, Chufang; Shi, Yi; Shi, Xuanling; Gao, George F.; Xiang, Ye; Qiu, Xiangguo; Chen, Ling; Zhang, Linqi

    2016-01-01

    Ebola virus infections cause a deadly hemorrhagic disease for which no vaccines or therapeutics has received regulatory approval. Here we show isolation of three (Q206, Q314 and Q411) neutralizing monoclonal antibodies (mAbs) against the surface glycoprotein (GP) of Ebola virus identified in West Africa in 2014 through sequential immunization of Chinese rhesus macaques and antigen-specific single B cell sorting. These mAbs demonstrated potent neutralizing activities against both pseudo and live Ebola virus independent of complement. Biochemical, single particle EM, and mutagenesis analysis suggested Q206 and Q411 recognized novel epitopes in the head while Q314 targeted the glycan cap in the GP1 subunit. Q206 and Q411 appeared to influence GP binding to its receptor NPC1. Treatment with these mAbs provided partial but significant protection against disease in a mouse model of Ebola virus infection. These novel mAbs could serve as promising candidates for prophylactic and therapeutic interventions against Ebola virus infection. PMID:27181584

  6. Review: Occult hepatitis C virus infection: still remains a controversy.

    PubMed

    Vidimliski, Pavlina Dzekova; Nikolov, Igor; Geshkovska, Nadica Matevska; Dimovski, Aleksandar; Rostaing, Lionel; Sikole, Aleksandar

    2014-09-01

    Occult hepatitis C virus (HCV) infection is characterized by the presence of HCV RNA in the liver cells or peripheral blood mononuclear cells of the patients whose serum samples test negative for HCV RNA, with or without presence of HCV antibodies. The present study reviews the existing literature on the persistence of occult hepatitis C virus infection, with description of the clinical characteristics and methods for identification of occult hepatitis C. Occult hepatitis C virus infection was detected in patients with abnormal results of liver function tests of unknown origin, with HCV antibodies and HCV RNA negativity in serum, and also in patients with spontaneous or treatment-induced recovery from hepatitis C. The viral replication in the liver cells and/or peripheral blood mononuclear cells was present in all clinical presentations of occult hepatitis C. The peripheral blood mononuclear cells represent an extra-hepatic site of HCV replication. The reason why HCV RNA was not detectable in the serum of patients with occult hepatitis C, could be the low number of circulating viral particles not detectable by the diagnostic tests with low sensitivity. It is uncertain whether occult hepatitis C is a different clinical entity or just a form of chronic hepatitis C virus infection. Data accumulated over the last decade demonstrated that an effective approach to the diagnosis of HCV infection would be the implementation of more sensitive HCV RNA diagnostic assays, and also, examination of the presence of viral particles in the cells of the immune system.

  7. Virus Infections on Prion Diseased Mice Exacerbate Inflammatory Microglial Response

    PubMed Central

    Lins, Nara; Mourão, Luiz; Trévia, Nonata; Passos, Aline; Farias, José Augusto; Assunção, Jarila; Bento-Torres, João; Consentino Kronka Sosthenes, Marcia; Diniz, José Antonio Picanço; Vasconcelos, Pedro Fernando da Costa

    2016-01-01

    We investigated possible interaction between an arbovirus infection and the ME7 induced mice prion disease. C57BL/6, females, 6-week-old, were submitted to a bilateral intrahippocampal injection of ME7 prion strain (ME7) or normal brain homogenate (NBH). After injections, animals were organized into two groups: NBH (n = 26) and ME7 (n = 29). At 15th week after injections (wpi), animals were challenged intranasally with a suspension of Piry arbovirus 0.001% or with NBH. Behavioral changes in ME7 animals appeared in burrowing activity at 14 wpi. Hyperactivity on open field test, errors on rod bridge, and time reduction in inverted screen were detected at 15th, 19th, and 20th wpi respectively. Burrowing was more sensitive to earlier hippocampus dysfunction. However, Piry-infection did not significantly affect the already ongoing burrowing decline in the ME7-treated mice. After behavioral tests, brains were processed for IBA1, protease-resistant form of PrP, and Piry virus antigens. Although virus infection in isolation did not change the number of microglia in CA1, virus infection in prion diseased mice (at 17th wpi) induced changes in number and morphology of microglia in a laminar-dependent way. We suggest that virus infection exacerbates microglial inflammatory response to a greater degree in prion-infected mice, and this is not necessarily correlated with hippocampal-dependent behavioral deficits. PMID:28003864

  8. Epidemiological and Virological Characterization of Influenza B Virus Infections

    PubMed Central

    Sharabi, Sivan; Drori, Yaron; Micheli, Michal; Friedman, Nehemya; Orzitzer, Sara; Bassal, Ravit; Glatman-Freedman, Aharona; Shohat, Tamar; Mendelson, Ella; Hindiyeh, Musa; Mandelboim, Michal

    2016-01-01

    While influenza A viruses comprise a heterogeneous group of clinically relevant influenza viruses, influenza B viruses form a more homogeneous cluster, divided mainly into two lineages: Victoria and Yamagata. This divergence has complicated seasonal influenza vaccine design, which traditionally contained two seasonal influenza A virus strains and one influenza B virus strain. We examined the distribution of the two influenza B virus lineages in Israel, between 2011–2014, in hospitalized and in non-hospitalized (community) influenza B virus-infected patients. We showed that influenza B virus infections can lead to hospitalization and demonstrated that during some winter seasons, both influenza B virus lineages circulated simultaneously in Israel. We further show that the influenza B virus Yamagata lineage was dominant, circulating in the county in the last few years of the study period, consistent with the anti-Yamagata influenza B virus antibodies detected in the serum samples of affected individuals residing in Israel in the year 2014. Interestingly, we found that elderly people were particularly vulnerable to Yamagata lineage influenza B virus infections. PMID:27533045

  9. Biomarkers in Japanese Encephalitis: A Review

    PubMed Central

    Kant Upadhyay, Ravi

    2013-01-01

    JE is a flavivirus generated dreadful CNS disease which causes high mortality in various pediatric groups. JE disease is currently diagnosed by measuring the level of viral antigens and virus neutralization IgM antibodies in blood serum and CSF by ELISA. However, it is not possible to measure various disease-identifying molecules, structural and molecular changes occurred in tissues, and cells by using such routine methods. However, few important biomarkers such as cerebrospinal fluid, plasma, neuro-imaging, brain mapping, immunotyping, expression of nonstructural viral proteins, systematic mRNA profiling, DNA and protein microarrays, active caspase-3 activity, reactive oxygen species and reactive nitrogen species, levels of stress-associated signaling molecules, and proinflammatory cytokines could be used to confirm the disease at an earlier stage. These biomarkers may also help to diagnose mutant based environment specific alterations in JEV genotypes causing high pathogenesis and have immense future applications in diagnostics. There is an utmost need for the development of new more authentic, appropriate, and reliable physiological, immunological, biochemical, biophysical, molecular, and therapeutic biomarkers to confirm the disease well in time to start the clinical aid to the patients. Hence, the present review aims to discuss new emerging biomarkers that could facilitate more authentic and fast diagnosis of JE disease and its related disorders in the future. PMID:24455705

  10. Mumps encephalitis with akinesia and mutism.

    PubMed

    Suga, Kenichi; Goji, Aya; Shono, Miki; Matsuura, Sato; Inoue, Miki; Toda, Eiko; Miyazaki, Tatsushi; Kawahito, Masami; Mori, Kazuhiro

    2015-08-01

    Measles-rubella-mumps vaccination is routine in many countries, but the mumps vaccine remains voluntary and is not covered by insurance in Japan. A 5-year-old Japanese boy who had not received the mumps vaccine was affected by mumps parotitis. Several days later, he presented with various neurological abnormalities, including akinesia, mutism, dysphagia, and uncontrolled respiratory disorder. Mumps encephalitis was diagnosed. Despite steroid pulse and immunoglobulin treatment, the disease progressed. Magnetic resonance imaging showed necrotic changes in bilateral basal ganglia, midbrain, and hypothalamus. At 1 year follow up, he was bedridden and required enteral feeding through a gastric fistula and tracheostomy. Mumps vaccination should be made routine as soon as possible in Japan, because mumps encephalitis carries the risk of severe sequelae.

  11. Dengue fever virus and Japanese encephalitis virus synthetic peptides, with motifs to fit HLA class I haplotypes prevalent in human populations in endemic regions, can be used for application to skin Langerhans cells to prime antiviral CD8+ cytotoxic T cells (CTLs)--a novel approach to the protection of humans.

    PubMed

    Becker, Y

    1994-09-01

    Flaviviruses were reported to induce CD8+ cytotoxic T cells in infected individuals, indicating that nonapeptides, proteolytic cleavage products of the viral precursor protein, enter the endoplasmic reticulum in infected cells and interact with HLA class I molecules. The assembled HLA class I molecules are transported to the plasma membrane and prime CD8+ T cells. Current knowledge of the interaction of viral peptides with HLA molecules is reviewed. Based on this review, an idea is presented to use synthetic flavivirus peptides with an amino acid motif to fit with the HLA class I peptide binding group of HLA haplotypes prevalent in a given population in an endemic area. These synthetic viral peptides may be introduced into the human skin using a lotion containing the peptides ("Peplotion") together with substances capable of enhancing the penetration of these peptides into the skin to reach Langerhans cells. The peptide-treated Langerhans cells, professional antigen-presenting cells, may bind the synthetic viral peptides by their HLA class I peptide-binding grooves. Antigens carrying Langerhans cells are able to migrate and induce the cellular immune response in the lymph nodes. This approach to the priming of antiviral CD8+ cytotoxic T cells may provide cellular immune protection from flavivirus infection without inducing the humoral immune response, which can lead to the shock syndrome in Dengue fever patients. To be able to develop anti-Dengue virus synthetic peptides for populations with different HLA class I haplotypes, it is necessary to develop computational studies to design HLA class I Dengue virus synthetic peptides with motifs to fit the HLA haplotypes of the population living in an endemic region for Dengue fever. Experiments to study Dengue virus and Japanese encephalitis peptides vaccines and their effectiveness in protection against Dengue fever and Japanese encephalitis are needed. The development of human antiviral vaccines for application of viral

  12. Bilateral Linear Lichen Planus Pigmentosus Associated with Hepatitis C Virus Infection.

    PubMed

    Vachiramon, Vasanop; Suchonwanit, Poonkiat; Thadanipon, Kunlawat

    2010-09-11

    Lichen planus pigmentosus is a rare subtype of lichen planus. We report a first case of lichen planus pigmentosus with bilateral linear distribution associated with hepatitis C virus infection. The lesion was improved after sun avoidance and treatment of hepatitis C virus infection with a combination of interferon and ribavirin. This case stresses the importance of screening for hepatitis C virus infection as lichen planus pigmentosus can be an associated condition.

  13. Bilateral Linear Lichen Planus Pigmentosus Associated with Hepatitis C Virus Infection

    PubMed Central

    Vachiramon, Vasanop; Suchonwanit, Poonkiat; Thadanipon, Kunlawat

    2010-01-01

    Lichen planus pigmentosus is a rare subtype of lichen planus. We report a first case of lichen planus pigmentosus with bilateral linear distribution associated with hepatitis C virus infection. The lesion was improved after sun avoidance and treatment of hepatitis C virus infection with a combination of interferon and ribavirin. This case stresses the importance of screening for hepatitis C virus infection as lichen planus pigmentosus can be an associated condition. PMID:21060775

  14. Immunophenotyping of inflammatory cells associated with Schmallenberg virus infection of the central nervous system of ruminants.

    PubMed

    Herder, Vanessa; Hansmann, Florian; Wohlsein, Peter; Peters, Martin; Varela, Mariana; Palmarini, Massimo; Baumgärtner, Wolfgang

    2013-01-01

    Schmallenberg virus (SBV) is a recently discovered Bunyavirus associated mainly with abortions, stillbirths and malformations of the skeletal and central nervous system (CNS) in newborn ruminants. In this study, a detailed immunophenotyping of the inflammatory cells of the CNS of affected animals was carried out in order to increase our understanding of SBV pathogenesis. A total of 82 SBV-polymerase chain reaction (PCR) positive neonatal ruminants (46 sheep lambs, 34 calves and 2 goat kids) were investigated for the presence of inflammation in the brain and spinal cord. The study focused on 15 out of 82 animals (18.3%) showing inflammation in the CNS. All 15 neonates displayed lymphohistiocytic meningoencephalomyelitis affecting most frequently the mesencephalon and the parietal and temporal lobes. The majority of infiltrating cells were CD3-positive T cells, followed by CD79α-positive B cells and CD68-positive microglia/macrophages. Malformations like por- and hydranencephaly, frequently found in the temporal lobe, showed associated demyelination and axonal loss. SBV antigen was detected in 37 out of 82 (45.1%) neonatal brains by immunohistochemistry. In particular, SBV antigen was found in 93.3% (14 out of 15 ruminants) and 32.8% (22 out of 67 ruminants) of animals with and without encephalitis, respectively. Highest amounts of virus-protein expression levels were found in the temporal lobe. Our findings suggest that: (i) different brain regions display differential susceptibility to SBV infection; (ii) inflammatory cells in the CNS are found only in a minority of virus infected animals; (iii) malformations occur in association with and without inflammation in the CNS; and (iv) viral antigen is strongly associated with the presence of inflammation in naturally infected animals. Further studies are required to explore the cell tropism and pathogenesis of SBV infection in ruminants.

  15. Eastern Equine Encephalitis

    MedlinePlus

    ... Facebook Tweet Share Compartir Image of Culiseta melanura mosquito, photo taken by Jason Williams, reproduced by permission from the Virginia Mosquito Control Association. Eastern equine encephalitis virus (EEEV) is ...

  16. Encephalitis (For Parents)

    MedlinePlus

    ... Encephalitis can be a very rare complication of Lyme disease transmitted by ticks or of rabies spread by ... MORE ON THIS TOPIC West Nile Virus Chickenpox Lyme Disease Fever and Taking Your Child's Temperature What's West ...

  17. Animal Models of Respiratory Syncytial Virus Infection and Disease

    PubMed Central

    Sacco, Randy E.; Durbin, Russell K.; Durbin, Joan E.

    2015-01-01

    The study of human respiratory syncytial virus pathogenesis and immunity has been hampered by its exquisite host specificity, and the difficulties encountered in adapting this virus to a murine host. The reasons for this obstacle are not well understood, but appear to reflect, at least in part, the inability of the virus to block the interferon response in any but the human host. This review addresses some of the issues encountered in mouse models of respiratory syncytial virus infection, and describes the advantages and disadvantages of alternative model systems. PMID:26176495

  18. A case of Mayaro virus infection imported from French Guiana.

    PubMed

    Llagonne-Barets, Marion; Icard, Vinca; Leparc-Goffart, Isabelle; Prat, Christine; Perpoint, Thomas; André, Patrice; Ramière, Christophe

    2016-04-01

    Emergence of arboviruses is a rising problem in several areas in the world. Here we report a case of Mayaro virus infection that was diagnosed in a French citizen presenting a dengue-like syndrome with prolonged arthralgia following a travel in French Guiana. Diagnosis was based on serological testing, a newly developed specific RT-PCR and sequencing. The real incidence of this viral infection among travelers is poorly known but this case is the first reported in a European area where Aedes albopictus mosquitoes are established, which underscores the necessity to determine the vector competence of the European strain of this mosquito species for Mayaro virus.

  19. Persistent RNA virus infections: do PAMPS drive chronic disease?

    PubMed

    McCarthy, Mary K; Morrison, Thomas E

    2017-02-16

    Chronic disease associated with persistent RNA virus infections represents a key public health concern. While human immunodeficiency virus-1 and hepatitis C virus are perhaps the most well-known examples of persistent RNA viruses that cause chronic disease, evidence suggests that many other RNA viruses, including re-emerging viruses such as chikungunya virus, Ebola virus and Zika virus, establish persistent infections. The mechanisms by which RNA viruses drive chronic disease are poorly understood. Here, we discuss how the persistence of viral RNA may drive chronic disease manifestations via the activation of RNA sensing pathways.

  20. Genetic strategy to prevent influenza virus infections in animals.

    PubMed

    Chen, Jianzhu; Chen, Steve C-Y; Stern, Patrick; Scott, Benjamin B; Lois, Carlos

    2008-02-15

    The natural reservoirs of influenza viruses are aquatic birds. After adaptation, avian viruses can acquire the ability to infect humans and cause severe disease. Because domestic poultry serves as a key link between the natural reservoir of influenza viruses and epidemics and pandemics in human populations, an effective measure to control influenza would be to eliminate or reduce influenza virus infection in domestic poultry. The development and distribution of influenza-resistant poultry represents a proactive strategy for controlling the origin of influenza epidemics and pandemics in both poultry and human populations. Recent developments in RNA interference and transgenesis in birds should facilitate the development of influenza-resistant poultry.

  1. Neutralization Assay for Chikungunya Virus Infection: Plaque Reduction Neutralization Test.

    PubMed

    Azami, Nor Azila Muhammad; Moi, Meng Ling; Takasaki, Tomohiko

    2016-01-01

    Neutralization assay is a technique that detects and quantifies neutralizing antibody in serum samples by calculating the percentage of reduction of virus activity, as the concentration of virus used is usually constant. Neutralizing antibody titer is conventionally determined by calculating the percentage reduction in total virus infectivity by counting and comparing number of plaques (localized area of infection due to cytopathic effect) with a standard amount of virus. Conventional neutralizing test uses plaque-reduction neutralization test (PRNT) to determine neutralizing antibody titers against Chikungunya virus (CHIKV). Here we describe the plaque reduction neutralization assay (PRNT) using Vero cell lines to obtain neutralizing antibody titers.

  2. A conservation law for virus infection kinetics in vitro.

    PubMed

    Kakizoe, Yusuke; Morita, Satoru; Nakaoka, Shinji; Takeuchi, Yasuhiro; Sato, Kei; Miura, Tomoyuki; Beauchemin, Catherine A A; Iwami, Shingo

    2015-07-07

    Conservation laws are among the most important properties of a physical system, but are not commonplace in biology. We derived a conservation law from the basic model for viral infections which consists in a small set of ordinary differential equations. We challenged the conservation law experimentally for the case of a virus infection in a cell culture. We found that the derived, conserved quantity remained almost constant throughout the infection period, implying that the derived conservation law holds in this biological system. We also suggest a potential use for the conservation law in evaluating the accuracy of experimental measurements.

  3. Multiphasic acute disseminated encephalomyelitis associated with atypical rubella virus infection.

    PubMed

    Shinoda, Koji; Asahara, Hideaki; Uehara, Taira; Miyoshi, Katsue; Suzuki, Satoshi O; Iwaki, Toru; Kira, Jun-ichi

    2015-02-01

    We report the first case of an occurrence of multiphasic acute disseminated encephalomyelitis (ADEM) associated with atypical rubella virus infection with no rash and long-term increased titers of serum anti-rubella IgM in a 17-year-old male who had no history of rubella vaccination. He suffered from at least six clinical exacerbations with disseminated hyperintense lesions on FLAIR MR images during the course of 18 months. Repeated methylprednisolone pulse therapy and intravenous immunoglobulin therapy resolved the exacerbations. In patients with multiphasic ADEM of unknown etiology, clinicians should also consider the possibility of preceding infection with rubella virus.

  4. Animal models of respiratory syncytial virus infection and disease.

    PubMed

    Sacco, Randy E; Durbin, Russell K; Durbin, Joan E

    2015-08-01

    The study of human respiratory syncytial virus pathogenesis and immunity has been hampered by its exquisite host specificity, and the difficulties encountered in adapting this virus to a murine host. The reasons for this obstacle are not well understood, but appear to reflect, at least in part, the inability of the virus to block the interferon response in any but the human host. This review addresses some of the issues encountered in mouse models of respiratory syncytial virus infection, and describes the advantages and disadvantages of alternative model systems.

  5. Possible Association Between Zika Virus Infection and Microcephaly - Brazil, 2015.

    PubMed

    Schuler-Faccini, Lavinia; Ribeiro, Erlane M; Feitosa, Ian M L; Horovitz, Dafne D G; Cavalcanti, Denise P; Pessoa, André; Doriqui, Maria Juliana R; Neri, Joao Ivanildo; Neto, Joao Monteiro de Pina; Wanderley, Hector Y C; Cernach, Mirlene; El-Husny, Antonette S; Pone, Marcos V S; Serao, Cassio L C; Sanseverino, Maria Teresa V

    2016-01-29

    In early 2015, an outbreak of Zika virus, a flavivirus transmitted by Aedes mosquitoes, was identified in northeast Brazil, an area where dengue virus was also circulating. By September, reports of an increase in the number of infants born with microcephaly in Zika virus-affected areas began to emerge, and Zika virus RNA was identified in the amniotic fluid of two women whose fetuses had been found to have microcephaly by prenatal ultrasound. The Brazil Ministry of Health (MoH) established a task force to investigate the possible association of microcephaly with Zika virus infection during pregnancy and a registry for incident microcephaly cases (head circumference ≥2 standard deviations [SD] below the mean for sex and gestational age at birth) and pregnancy outcomes among women suspected to have had Zika virus infection during pregnancy. Among a cohort of 35 infants with microcephaly born during August-October 2015 in eight of Brazil's 26 states and reported to the registry, the mothers of all 35 had lived in or visited Zika virus-affected areas during pregnancy, 25 (71%) infants had severe microcephaly (head circumference >3 SD below the mean for sex and gestational age), 17 (49%) had at least one neurologic abnormality, and among 27 infants who had neuroimaging studies, all had abnormalities. Tests for other congenital infections were negative. All infants had a lumbar puncture as part of the evaluation and cerebrospinal fluid (CSF) samples were sent to a reference laboratory in Brazil for Zika virus testing; results are not yet available. Further studies are needed to confirm the association of microcephaly with Zika virus infection during pregnancy and to understand any other adverse pregnancy outcomes associated with Zika virus infection. Pregnant women in Zika virus-affected areas should protect themselves from mosquito bites by using air conditioning, screens, or nets when indoors, wearing long sleeves and pants, using permethrin-treated clothing and gear

  6. Autoimmune lymphoproliferative syndrome mimicking chronic active Epstein-Barr virus infection.

    PubMed

    Nomura, Keiko; Kanegane, Hirokazu; Otsubo, Keisuke; Wakiguchi, Hiroshi; Noda, Yukihiro; Kasahara, Yoshihito; Miyawaki, Toshio

    2011-06-01

    Chronic active Epstein-Barr virus infection (CAEBV) is defined as a systemic EBV-associated lymphoproliferative disease characterized by fever, lymphadenopathy, and splenomegaly in apparently immunocompetent persons. Recent studies have revealed that EBV infects T or natural killer cells in most patients with CAEBV; the etiology of CAEBV, however, remains unknown. Autoimmune lymphoproliferative disorder (ALPS) is an inherited disorder associated with defects in apoptosis, and clinically characterized by lymphadenopathy, splenomegaly, hypergammaglobulinemia, and autoimmune disease. ALPS is most often associated with mutations in the FAS gene, which is an apoptosis-signaling receptor important for homeostasis of the immune system. Based on the clinical similarity between ALPS and CAEBV with respect to lymphoproliferation, we have examined the possibility of the co-occurrence of ALPS in patients with a diagnosis of CAEBV. In this study, we have identified FAS gene mutations in three Japanese patients with lymphadenopathy, hepatosplenomegaly, and unusual EBV infection, who were diagnosed with CAEBV. These observations, which indicate that the clinical development of ALPS may be associated with EBV infection, alert us to a potential diagnostic pitfall of CAEBV.

  7. Auto-immune encephalitis as differential diagnosis of infectious encephalitis

    PubMed Central

    Armangue, Thaís; Leypoldt, Frank; Dalmau, Josep

    2014-01-01

    Purpose of review To describe the main types of autoimmune encephalitis with special emphasis on those associated with antibodies against neuronal cell surface or synaptic proteins, and the differential diagnosis with infectious encephalitis. Recent findings There is a continuous expansion of the number of cell surface or synaptic proteins that are targets of autoimmunity. The most recently identified include the mGluR5, DPPX, and the GABAAR. In these and previously known autoimmune encephalitis (NMDAR, AMPAR, GABABR, LGI1, CASPR2), the prodromal symptoms or types of presentations often suggest a viral encephalitis. We review here clues that help in the differential diagnosis with infectious encephalitis. Moreover, recent investigations indicate that viral encephalitis (e.g., herpes simplex) can trigger synaptic autoimmunity. In all these disorders immunotherapy is usually effective. Summary Autoimmune encephalitis comprises an expanding group of potentially treatable disorders that should be included in the differential diagnosis of any type of encephalitis. PMID:24792345

  8. Mayaro virus infection cycle relies on casein kinase 2 activity.

    PubMed

    Barroso, Madalena M S; Lima, Carla S; Silva-Neto, Mário A C; Da Poian, Andrea T

    2002-09-06

    Replication of Mayaro virus in Vero cells induces dramatic cytopathic effects and cell death. In this study, we have evaluated the role of casein kinase 2 (CK2) during Mayaro virus infection cycle. We found that CK2 was activated during the initial stages of infection ( approximately 36% after 4h). This activation was further confirmed when the enzyme was partially purified from the cellular lysate either by Mono Q 5/5Hr column or heparin-agarose column. Using this later column, we found that the elution profile of CK2 activity from infected cells was different from that obtained for control cell enzyme, suggesting a structural modification of CK2 after infection. Treatment of infected cells with a cell-permeable inhibitor of CK2, dichloro-1-(beta-D-ribofuranosyl)benzimidazole (DRB), abolished the cytopathic effect in a dose-dependent manner. Together this set of data demonstrates for the first time that CK2 activity in host cells is required in Mayaro virus infection cycle.

  9. Discovery of mammalian genes that participate in virus infection

    PubMed Central

    Organ, Edward L; Sheng, Jinsong; Ruley, H Earl; Rubin, Donald H

    2004-01-01

    Background Viruses are obligate intracellular parasites that rely upon the host cell for different steps in their life cycles. The characterization of cellular genes required for virus infection and/or cell killing will be essential for understanding viral life cycles, and may provide cellular targets for new antiviral therapies. Results Candidate genes required for lytic reovirus infection were identified by tagged sequence mutagenesis, a process that permits rapid identification of genes disrupted by gene entrapment. One hundred fifty-one reovirus resistant clones were selected from cell libraries containing 2 × 105 independently disrupted genes, of which 111 contained mutations in previously characterized genes and functionally anonymous transcription units. Collectively, the genes associated with reovirus resistance differed from genes targeted by random gene entrapment in that known mutational hot spots were under represented, and a number of mutations appeared to cluster around specific cellular processes, including: IGF-II expression/signalling, vesicular transport/cytoskeletal trafficking and apoptosis. Notably, several of the genes have been directly implicated in the replication of reovirus and other viruses at different steps in the viral lifecycle. Conclusions Tagged sequence mutagenesis provides a rapid, genome-wide strategy to identify candidate cellular genes required for virus infection. The candidate genes provide a starting point for mechanistic studies of cellular processes that participate in the virus lifecycle and may provide targets for novel anti-viral therapies. PMID:15522117

  10. Dengue Virus Infection Perturbs Lipid Homeostasis in Infected Mosquito Cells

    SciTech Connect

    Perera, Rushika M.; Riley, Catherine; Isaac, Georgis; Hopf- Jannasch, Amber; Moore, Ronald J.; Weitz, Karl K.; Pasa-Tolic, Ljiljana; Metz, Thomas O.; Adamec, Jiri; Kuhn, Richard J.

    2012-03-22

    Dengue virus causes {approx}50-100 million infections per year and thus is considered one of the most aggressive arthropod-borne human pathogen worldwide. During its replication, dengue virus induces dramatic alterations in the intracellular membranes of infected cells. This phenomenon is observed both in human and vector-derived cells. Using high-resolution mass spectrometry of mosquito cells, we show that this membrane remodeling is directly linked to a unique lipid repertoire induced by dengue virus infection. Specifically, 15% of the metabolites detected were significantly different between DENV infected and uninfected cells while 85% of the metabolites detected were significantly different in isolated replication complex membranes. Furthermore, we demonstrate that intracellular lipid redistribution induced by the inhibition of fatty acid synthase, the rate-limiting enzyme in lipid biosynthesis, is sufficient for cell survival but is inhibitory to dengue virus replication. Lipids that have the capacity to destabilize and change the curvature of membranes as well as lipids that change the permeability of membranes are enriched in dengue virus infected cells. Several sphingolipids and other bioactive signaling molecules that are involved in controlling membrane fusion, fission, and trafficking as well as molecules that influence cytoskeletal reorganization are also up regulated during dengue infection. These observations shed light on the emerging role of lipids in shaping the membrane and protein environments during viral infections and suggest membrane-organizing principles that may influence virus-induced intracellular membrane architecture.

  11. Antiviral activity of lanatoside C against dengue virus infection.

    PubMed

    Cheung, Yan Yi; Chen, Karen Caiyun; Chen, Huixin; Seng, Eng Khuan; Chu, Justin Jang Hann

    2014-11-01

    Dengue infection poses a serious threat globally due to its recent rapid spread and rise in incidence. Currently, there is no approved vaccine or effective antiviral drug for dengue virus infection. In response to the urgent need for the development of an effective antiviral for dengue virus, the US Drug Collection library was screened in this study to identify compounds with anti-dengue activities. Lanatoside C, an FDA approved cardiac glycoside was identified as a candidate anti-dengue compound. Our data revealed that lanatoside C has an IC50 of 0.19μM for dengue virus infection in HuH-7 cells. Dose-dependent reduction in dengue viral RNA and viral proteins synthesis were also observed upon treatment with increasing concentrations of lanatoside C. Time of addition study indicated that lanatoside C inhibits the early processes of the dengue virus replication cycle. Furthermore, lanatoside C can effectively inhibit all four serotypes of dengue virus, flavivirus Kunjin, alphavirus Chikungunya and Sindbis virus as well as the human enterovirus 71. These findings suggest that lanatoside C possesses broad spectrum antiviral activity against several groups of positive-sense RNA viruses.

  12. Puumala virus infections in Finland: increased occupational risk for farmers.

    PubMed

    Vapalahti, K; Paunio, M; Brummer-Korvenkontio, M; Vaheri, A; Vapalahti, O

    1999-06-15

    Puumala hantavirus, transmitted by bank voles (Clethrionomys glareolus), causes a mild-type hemorrhagic fever with renal syndrome. The disease is common in Finland and is considered an occupational hazard for farmers, but the actual risk has not been assessed by analytical studies. Data on 5,132 serologically confirmed Puumala virus infections during 1989-1994 were analyzed, and cases among farmers and the population living in similar conditions were compared. The farmers contracted the disease earlier and more often than did the comparison group. In the province of Mikkeli with the highest incidence (70/100,000), the risk ratio was 5.1 (95% confidence interval (CI) 3.0-8.4) for 20- to 29-year-old farmers; in the older age groups, the risk was still increased but the risk ratios were lower. The peak incidence in the comparison group was 10 years later (age group 30-39 years). For the whole country, the result was similar although less marked. The average risk ratio adjusted by age, sex, and geographic variation was 1.7 (95% CI 1.5-1.8) for the whole country and 1.9 (95% CI 1.5-2.3) for the Mikkeli province, where 80% of Puumala virus infections among young farmers could be estimated to be attributable to occupation.

  13. Influenza A virus infections in swine: pathogenesis and diagnosis.

    PubMed

    Janke, B H

    2014-03-01

    Influenza has been recognized as a respiratory disease in swine since its first appearance concurrent with the 1918 "Spanish flu" human pandemic. All influenza viruses of significance in swine are type A, subtype H1N1, H1N2, or H3N2 viruses. Influenza viruses infect epithelial cells lining the surface of the respiratory tract, inducing prominent necrotizing bronchitis and bronchiolitis and variable interstitial pneumonia. Cell death is due to direct virus infection and to insult directed by leukocytes and cytokines of the innate immune system. The most virulent viruses consistently express the following characteristics of infection: (1) higher or more prolonged virus replication, (2) excessive cytokine induction, and (3) replication in the lower respiratory tract. Nearly all the viral proteins contribute to virulence. Pigs are susceptible to infection with both human and avian viruses, which often results in gene reassortment between these viruses and endemic swine viruses. The receptors on the epithelial cells lining the respiratory tract are major determinants of infection by influenza viruses from other hosts. The polymerases, especially PB2, also influence cross-species infection. Methods of diagnosis and characterization of influenza viruses that infect swine have improved over the years, driven both by the availability of new technologies and by the necessity of keeping up with changes in the virus. Testing of oral fluids from pigs for virus and antibody is a recent development that allows efficient sampling of large numbers of animals.

  14. The heat shock response restricts virus infection in Drosophila

    PubMed Central

    Merkling, Sarah H.; Overheul, Gijs J.; van Mierlo, Joël T.; Arends, Daan; Gilissen, Christian; van Rij, Ronald P.

    2015-01-01

    Innate immunity is the first line of defence against pathogens and is essential for survival of the infected host. The fruit fly Drosophila melanogaster is an emerging model to study viral pathogenesis, yet antiviral defence responses remain poorly understood. Here, we describe the heat shock response, a cellular mechanism that prevents proteotoxicity, as a component of the antiviral immune response in Drosophila. Transcriptome analyses of Drosophila S2 cells and adult flies revealed strong induction of the heat shock response upon RNA virus infection. Dynamic induction patterns of heat shock pathway components were characterized in vitro and in vivo following infection with different classes of viruses. The heat shock transcription factor (Hsf), as well as active viral replication, were necessary for the induction of the response. Hsf-deficient adult flies were hypersensitive to virus infection, indicating a role of the heat shock response in antiviral defence. In accordance, transgenic activation of the heat shock response prolonged survival time after infection and enabled long-term control of virus replication to undetectable levels. Together, our results establish the heat shock response as an important constituent of innate antiviral immunity in Drosophila. PMID:26234525

  15. ZIKA VIRUS INFECTION; VERTICAL TRANSMISSION AND FOETAL CONGENITAL ANOMALIES.

    PubMed

    Abbasi, Aziz-un-Nisa

    2016-01-01

    Zika virus (ZIKV) is an arbovirus belonging to flaviviridae family that includes Dengue, West Nile, and Yellow Fever among others. Zika virus was first discovered in 1947 in Zika forest of Uganda. It is a vector borne disease, which has been sporadically reported mostly from Africa, Pacific islands and Southeast Asia since its discovery. ZIKV infection presents as a mild illness with symptoms lasting for several days to a week after the bite of an infected mosquito. Majority of the patients have low grade fever, rash, headaches, joints pain, myalgia, and flu like symptoms. Pregnant women are more vulnerable to ZIKV infection and serious congenital anomalies can occur in foetus through trans-placental transmission. The gestation at which infection is acquired is important. Zika virus infection acquired in early pregnancy poses greater risk. There is no evidence so far about transmission through breast milk. Foetal microcephaly, Gillian Barre syndrome and other neurological and autoimmune syndromes have been reported in areas where Zika outbreaks have occurred. As infection is usually very mild no specific treatment is required. Pregnant women may be advised to take rest, get plenty of fluids. For fever and pain they can take antipyretics like paracetamol. So far no specific drugs or vaccines are available against Zika Virus Infection so prevention is the mainstay against this diseases. As ZIKV infection is a vector borne disease, prevention can be a multi-pronged strategy. These entail vector control interventions, personal protection, environmental sanitation and health education among others.

  16. Severe Sepsis and Septic Shock Associated with Chikungunya Virus Infection, Guadeloupe, 2014.

    PubMed

    Rollé, Amélie; Schepers, Kinda; Cassadou, Sylvie; Curlier, Elodie; Madeux, Benjamin; Hermann-Storck, Cécile; Fabre, Isabelle; Lamaury, Isabelle; Tressières, Benoit; Thiery, Guillaume; Hoen, Bruno

    2016-05-01

    During a 2014 outbreak, 450 patients with confirmed chikungunya virus infection were admitted to the University Hospital of Pointe-à-Pitre, Guadeloupe. Of these, 110 were nonpregnant adults; 42 had severe disease, and of those, 25 had severe sepsis or septic shock and 12 died. Severe sepsis may be a rare complication of chikungunya virus infection.

  17. Alexander the Great and West Nile Virus Encephalitis

    PubMed Central

    Marr, John S.

    2003-01-01

    Alexander the Great died in Babylon in 323 BC. His death at age 32 followed a 2-week febrile illness. Speculated causes of death have included poisoning, assassination, and a number of infectious diseases. One incident, mentioned by Plutarch but not considered by previous investigators, may shed light on the cause of Alexander’s death. The incident, which occurred as he entered Babylon, involved a flock of ravens exhibiting unusual behavior and subsequently dying at his feet. The inexplicable behavior of ravens is reminiscent of avian illness and death weeks before the first human cases of West Nile virus infection were identified in the United States. We posit that Alexander may have died of West Nile encephalitis. PMID:14725285

  18. Genetics Home Reference: X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia

    MedlinePlus

    ... X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia Enable Javascript to view the ... X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia (typically known by the acronym ...

  19. Influenza virus infections in the tropics during the first year of life.

    PubMed

    Libraty, Daniel H; Zhang, Lei; Caponpon, Mercydina; Capeding, Rosario Z

    2015-08-01

    Pediatric influenza virus infections in the tropics, particularly during infancy, are not well described. We identified influenza virus infections among infants with non-dengue acute undifferentiated febrile illnesses in San Pablo, Laguna, Philippines, as part of an ongoing clinical study of dengue virus infections during infancy. We found that 31% of infants with non-dengue acute undifferentiated febrile illnesses in San Pablo, Laguna, Philippines, had influenza virus infections. The majority were influenza A virus infections and outpatient cases. The infant ages were 11.1 [9.8-13.0] months (median [95% confidence interval]), and the cases clustered between June and December. Influenza episodes are a common cause of non-dengue acute undifferentiated febrile illnesses in the tropics during the first year of life.

  20. Central nervous system herpes simplex virus infection in afebrile children with seizures.

    PubMed

    Majumdar, Indrajit; Hartley-McAndrew, Michelle E; Weinstock, Arie L

    2012-04-01

    Central nervous system herpes simplex virus infection is suspected in patients presenting with acute-onset seizures and lethargy. The potential neurologic sequelae from untreated herpes infection can prompt empirical acyclovir therapy, even in afebrile subjects. The objectives of this study were to determine the frequency of central nervous system herpes simplex virus infection in children presenting with afebrile seizures and to assess the need for empirical acyclovir therapy. Clinical and laboratory data of children with acute-onset afebrile seizures and children with central nervous system herpes simplex virus infection were compared. Polymerase chain reaction and viral cultures of the cerebrospinal fluid for herpes simplex virus infection were negative in all subjects with afebrile seizures; 32.7% of these subjects were empirically treated with acyclovir. In conclusion, central nervous system herpes simplex virus infection is uncommon in children presenting with afebrile seizures, and acyclovir therapy is rarely necessary in subjects with normal neurologic examination and cerebrospinal fluid analysis.

  1. 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.

  2. Autoimmune encephalitis update

    PubMed Central

    Dalmau, Josep; Rosenfeld, Myrna R.

    2014-01-01

    Cancer-associated immune-mediated disorders of the central nervous system are a heterogeneous group. These disorders include the classic paraneoplastic neurologic disorders and the more recently described autoimmune encephalitis associated with antibodies to neuronal cell-surface or synaptic receptors that occur with and without a cancer association. Autoimmune encephalitis is increasingly recognized as the cause of a variety of neuropsychiatric syndromes that can be severe and prolonged. In contrast to the classic paraneoplastic disorders that are poorly responsive to tumor treatment and immunotherapy, autoimmune encephalitis often responds to these treatments, and patients can have full or marked recoveries. As early treatment speeds recovery, reduces disability, and decreases relapses that can occur in about 20% of cases, it is important that the immune pathogenesis of these disorders is recognized. PMID:24637228

  3. California encephalitis in Alabama.

    PubMed

    Mancao, M Y; Law, I M; Roberson-Trammell, K

    1996-10-01

    Arthropod-borne virus (arbovirus) infections in humans are primarily central nervous system infections, but other clinical manifestations include febrile illness and fever with hemorrhagic diathesis. In the genus Bunyavirus there are several viruses that cause disease in humans, especially in North America; these include LaCrosse, Jamestown Canyon, trivittatus, and snowshoe hare viruses. The disease seen mainly in children is California encephalitis (usually of the LaCrosse subtype); this infection is widespread in the United States but is most prevalent in the upper Midwest, especially in rural areas. We present the first reported case of California encephalitis in rural Alabama; the patient was a 7-year-old boy who came to us with fever and seizures in the summer of 1994. This report stresses the importance of including California encephalitis in the differential diagnosis when children have fever and altered sensorium after exposure to mosquitoes during summer months.

  4. Acute Human Inkoo and Chatanga Virus Infections, Finland.

    PubMed

    Putkuri, Niina; Kantele, Anu; Levanov, Lev; Kivistö, Ilkka; Brummer-Korvenkontio, Markus; Vaheri, Antti; Vapalahti, Olli

    2016-05-01

    Inkoo virus (INKV) and Chatanga virus (CHATV), which are circulating in Finland, are mosquitoborne California serogroup orthobunyaviruses that have a high seroprevalence among humans. Worldwide, INKV infection has been poorly described, and CHATV infection has been unknown. Using serum samples collected in Finland from 7,961 patients suspected of having viral neurologic disease or Puumala virus infection during the summers of 2001-2013, we analyzed the samples to detect California serogroup infections. IgM seropositivity revealed 17 acute infections, and cross-neutralization tests confirmed presence of INKV or CHATV infections. All children (<16 years of age) with INKV infection were hospitalized; adults were outpatients with mild disease, except for 1 who was hospitalized with CHATV infection. Symptoms included fever, influenza-like illness, nausea or vomiting, disorientation, nuchal rigidity, headache, drowsiness, and seizures. Although many INKV and CHATV infections appear to be subclinical, these viruses can cause more severe disease, especially in children.

  5. Deep sequencing in the management of hepatitis virus infections.

    PubMed

    Quer, Josep; Rodríguez-Frias, Francisco; Gregori, Josep; Tabernero, David; Soria, Maria Eugenia; García-Cehic, Damir; Homs, Maria; Bosch, Albert; Pintó, Rosa María; Esteban, Juan Ignacio; Domingo, Esteban; Perales, Celia

    2016-12-28

    The hepatitis viruses represent a major public health problem worldwide. Procedures for characterization of the genomic composition of their populations, accurate diagnosis, identification of multiple infections, and information on inhibitor-escape mutants for treatment decisions are needed. Deep sequencing methodologies are extremely useful for these viruses since they replicate as complex and dynamic quasispecies swarms whose complexity and mutant composition are biologically relevant traits. Population complexity is a major challenge for disease prevention and control, but also an opportunity to distinguish among related but phenotypically distinct variants that might anticipate disease progression and treatment outcome. Detailed characterization of mutant spectra should permit choosing better treatment options, given the increasing number of new antiviral inhibitors available. In the present review we briefly summarize our experience on the use of deep sequencing for the management of hepatitis virus infections, particularly for hepatitis B and C viruses, and outline some possible new applications of deep sequencing for these important human pathogens.

  6. The Impact of Wolbachia on Virus Infection in Mosquitoes

    PubMed Central

    Johnson, Karyn N.

    2015-01-01

    Mosquito-borne viruses such as dengue, West Nile and chikungunya viruses cause significant morbidity and mortality in human populations. Since current methods are not sufficient to control disease occurrence, novel methods to control transmission of arboviruses would be beneficial. Recent studies have shown that virus infection and transmission in insects can be impeded by co-infection with the bacterium Wolbachia pipientis. Wolbachia is a maternally inherited endosymbiont that is commonly found in insects, including a number of mosquito vector species. In Drosophila, Wolbachia mediates antiviral protection against a broad range of RNA viruses. This discovery pointed to a potential strategy to interfere with mosquito transmission of arboviruses by artificially infecting mosquitoes with Wolbachia. This review outlines research on the prevalence of Wolbachia in mosquito vector species and the impact of antiviral effects in both naturally and artificially Wolbachia-infected mosquitoes. PMID:26556361

  7. Genetic variation of occult hepatitis B virus infection

    PubMed Central

    Zhu, Hui-Lan; Li, Xu; Li, Jun; Zhang, Zhen-Hua

    2016-01-01

    Occult hepatitis B virus infection (OBI), characterized as the persistence of hepatitis B virus (HBV) surface antigen (HBsAg) seronegativity and low viral load in blood or liver, is a special form of HBV infection. OBI may be related mainly to mutations in the HBV genome, although the underlying mechanism of it remains to be clarified. Mutations especially within the immunodominant “α” determinant of S protein are “hot spots” that could contribute to the occurrence of OBI via affecting antigenicity and immunogenicity of HBsAg or replication and secretion of virion. Clinical reports account for a large proportion of previous studies on OBI, while functional analyses, especially those based on full-length HBV genome, are rare. PMID:27053845

  8. Pathology of Lassa virus infection in the rhesus monkey.

    PubMed

    Callis, R T; Jahrling, P B; DePaoli, A

    1982-09-01

    The clinical signs and gross and microscopic lesions of Lassa virus infection in the rhesus monkey are described. Of 17 monkeys infected with Lassa virus, nine died or were killed when moribund. The clinical signs were lethargy, aphagia, constipation, fever, conjunctivitis, and skin rash. Pulmonary congestion, pleural effusion, pericardial edema, hydropericardium, and a few visceral hemorrhages were present grossly. Major microscopic lesions were necrotizing hepatitis and interstitial pneumonia. Other microscopic changes were present in the heart, small intestine, spleen, lymph nodes, kidney, urinary bladder, adrenal glands, and central nervous system; however, most of these lesions were mild. In fact, death could not always be attributed to the morphologic changes; therefore, function alterations must be examined.

  9. Epidemiology of hepatitis A virus infections, Germany, 2007-2008.

    PubMed

    Faber, Mirko S; Stark, Klaus; Behnke, Susanne C; Schreier, Eckart; Frank, Christina

    2009-11-01

    Approximately 60% of hepatitis A virus infections in Germany occur in persons without a travel history to disease-endemic areas and for whom sources of infection are unknown. Recommendation of pretravel vaccination fails to prevent the remaining imported infections. Using enhanced surveillance in 2007-2008, we analyzed epidemiologic patterns of hepatitis A in Germany and appropriateness and adequacy of current immunization recommendations. Young patients with a migration background who had visited friends and family in their ancestral countries accounted for most imported cases. Phylogenetic analysis showed high diversity of sequence data and clustering of strains with similar regions of origin or patient migration backgrounds. Virologic findings are compatible with those of low-incidence countries, where virtually all infections are directly or indirectly imported from other regions. Germans with a migration background are seen as a special risk group so far insufficiently reached by pretravel vaccination advice.

  10. Aedes aegypti D7 Saliva Protein Inhibits Dengue Virus Infection

    PubMed Central

    Conway, Michael J.; Londono-Renteria, Berlin; Troupin, Andrea; Watson, Alan M.; Klimstra, William B.; Fikrig, Erol; Colpitts, Tonya M.

    2016-01-01

    Aedes aegypti is the primary vector of several medically relevant arboviruses including dengue virus (DENV) types 1–4. Ae. aegypti transmits DENV by inoculating virus-infected saliva into host skin during probing and feeding. Ae. aegypti saliva contains over one hundred unique proteins and these proteins have diverse functions, including facilitating blood feeding. Previously, we showed that Ae. aegypti salivary gland extracts (SGEs) enhanced dissemination of DENV to draining lymph nodes. In contrast, HPLC-fractionation revealed that some SGE components inhibited infection. Here, we show that D7 proteins are enriched in HPLC fractions that are inhibitory to DENV infection, and that recombinant D7 protein can inhibit DENV infection in vitro and in vivo. Further, binding assays indicate that D7 protein can directly interact with DENV virions and recombinant DENV envelope protein. These data reveal a novel role for D7 proteins, which inhibits arbovirus transmission to vertebrates through a direct interaction with virions. PMID:27632170

  11. Primary pulmonary hypertension associated with human immunodeficiency virus infection.

    PubMed Central

    Golpe, R.; Fernandez-Infante, B.; Fernandez-Rozas, S.

    1998-01-01

    Several cardiorespiratory diseases can complicate human immunodeficiency virus infection. Primary pulmonary hypertension is a rare clinical disorder which carries a bad prognosis. More than 90 cases of HIV-associated primary pulmonary hypertension have been reported to date. Although its pathogenesis remains unknown, some evidence suggests a possible role for the virus itself in its development. Genetic susceptibility may also be implicated. The clinical and histopathologic features of this entity do not differ from those of classic primary pulmonary hypertension. The diagnosis requires a high degree of clinical suspicion and a careful evaluation to rule out causes of secondary pulmonary hypertension. In addition to supportive measures, anticoagulation and vasodilators have been used to treat this disorder, although sufficient data regarding long-term results with these therapies are lacking. PMID:9799910

  12. Primary pulmonary hypertension associated with human immunodeficiency virus infection.

    PubMed

    Golpe, R; Fernandez-Infante, B; Fernandez-Rozas, S

    1998-07-01

    Several cardiorespiratory diseases can complicate human immunodeficiency virus infection. Primary pulmonary hypertension is a rare clinical disorder which carries a bad prognosis. More than 90 cases of HIV-associated primary pulmonary hypertension have been reported to date. Although its pathogenesis remains unknown, some evidence suggests a possible role for the virus itself in its development. Genetic susceptibility may also be implicated. The clinical and histopathologic features of this entity do not differ from those of classic primary pulmonary hypertension. The diagnosis requires a high degree of clinical suspicion and a careful evaluation to rule out causes of secondary pulmonary hypertension. In addition to supportive measures, anticoagulation and vasodilators have been used to treat this disorder, although sufficient data regarding long-term results with these therapies are lacking.

  13. Acute Human Inkoo and Chatanga Virus Infections, Finland

    PubMed Central

    Kantele, Anu; Levanov, Lev; Kivistö, Ilkka; Brummer-Korvenkontio, Markus; Vaheri, Antti; Vapalahti, Olli

    2016-01-01

    Inkoo virus (INKV) and Chatanga virus (CHATV), which are circulating in Finland, are mosquitoborne California serogroup orthobunyaviruses that have a high seroprevalence among humans. Worldwide, INKV infection has been poorly described, and CHATV infection has been unknown. Using serum samples collected in Finland from 7,961 patients suspected of having viral neurologic disease or Puumala virus infection during the summers of 2001–2013, we analyzed the samples to detect California serogroup infections. IgM seropositivity revealed 17 acute infections, and cross-neutralization tests confirmed presence of INKV or CHATV infections. All children (<16 years of age) with INKV infection were hospitalized; adults were outpatients with mild disease, except for 1 who was hospitalized with CHATV infection. Symptoms included fever, influenza-like illness, nausea or vomiting, disorientation, nuchal rigidity, headache, drowsiness, and seizures. Although many INKV and CHATV infections appear to be subclinical, these viruses can cause more severe disease, especially in children. PMID:27088268

  14. The Impact of Wolbachia on Virus Infection in Mosquitoes.

    PubMed

    Johnson, Karyn N

    2015-11-04

    Mosquito-borne viruses such as dengue, West Nile and chikungunya viruses cause significant morbidity and mortality in human populations. Since current methods are not sufficient to control disease occurrence, novel methods to control transmission of arboviruses would be beneficial. Recent studies have shown that virus infection and transmission in insects can be impeded by co-infection with the bacterium Wolbachia pipientis. Wolbachia is a maternally inherited endosymbiont that is commonly found in insects, including a number of mosquito vector species. In Drosophila, Wolbachia mediates antiviral protection against a broad range of RNA viruses. This discovery pointed to a potential strategy to interfere with mosquito transmission of arboviruses by artificially infecting mosquitoes with Wolbachia. This review outlines research on the prevalence of Wolbachia in mosquito vector species and the impact of antiviral effects in both naturally and artificially Wolbachia-infected mosquitoes.

  15. Background review for diagnostic test development for Zika virus infection

    PubMed Central

    Charrel, Rémi N; Leparc-Goffart, Isabelle; Pas, Suzan; de Lamballerie, Xavier; Koopmans, Marion; Reusken, Chantal

    2016-01-01

    Abstract Objective To review the state of knowledge about diagnostic testing for Zika virus infection and identify areas of research needed to address the current gaps in knowledge. Methods We made a non-systematic review of the published literature about Zika virus and supplemented this with information from commercial diagnostic test kits and personal communications with researchers in European preparedness networks. The review covered current knowledge about the geographical spread, pathogen characteristics, life cycle and infection kinetics of the virus. The available molecular and serological tests and biosafety issues are described and discussed in the context of the current outbreak strain. Findings We identified the following areas of research to address current knowledge gaps: (i) an urgent assessment of the laboratory capacity and capability of countries to detect Zika virus; (ii) rapid and extensive field validation of the available molecular and serological tests in areas with and without Zika virus transmission, with a focus on pregnant women; (iii) monitoring the genomic diversity of circulating Zika virus strains; (iv) prospective studies into the virus infection kinetics, focusing on diagnostic sampling (specimen types, combinations and timings); and (v) developing external quality assessments for molecular and serological testing, including differential diagnosis for similar viruses and symptom clusters. The availability of reagents for diagnostic development (virus strains and antigens, quantified viral ribonucleic acid) needs to be facilitated. Conclusion An international laboratory response is needed, including preparation of protocols for prospective studies to address the most pressing information needs. PMID:27516635

  16. Human Ebola virus infection results in substantial immune activation.

    PubMed

    McElroy, Anita K; Akondy, Rama S; Davis, Carl W; Ellebedy, Ali H; Mehta, Aneesh K; Kraft, Colleen S; Lyon, G Marshall; Ribner, Bruce S; Varkey, Jay; Sidney, John; Sette, Alessandro; Campbell, Shelley; Ströher, Ute; Damon, Inger; Nichol, Stuart T; Spiropoulou, Christina F; Ahmed, Rafi

    2015-04-14

    Four Ebola patients received care at Emory University Hospital, presenting a unique opportunity to examine the cellular immune responses during acute Ebola virus infection. We found striking activation of both B and T cells in all four patients. Plasmablast frequencies were 10-50% of B cells, compared with less than 1% in healthy individuals. Many of these proliferating plasmablasts were IgG-positive, and this finding coincided with the presence of Ebola virus-specific IgG in the serum. Activated CD4 T cells ranged from 5 to 30%, compared with 1-2% in healthy controls. The most pronounced responses were seen in CD8 T cells, with over 50% of the CD8 T cells expressing markers of activation and proliferation. Taken together, these results suggest that all four patients developed robust immune responses during the acute phase of Ebola virus infection, a finding that would not have been predicted based on our current assumptions about the highly immunosuppressive nature of Ebola virus. Also, quite surprisingly, we found sustained immune activation after the virus was cleared from the plasma, observed most strikingly in the persistence of activated CD8 T cells, even 1 mo after the patients' discharge from the hospital. These results suggest continued antigen stimulation after resolution of the disease. From these convalescent time points, we identified CD4 and CD8 T-cell responses to several Ebola virus proteins, most notably the viral nucleoprotein. Knowledge of the viral proteins targeted by T cells during natural infection should be useful in designing vaccines against Ebola virus.

  17. The Relationships between Respiratory Virus Infection and Aminotransferase in Children

    PubMed Central

    Oh, Jun Suk; Choi, Jun Sik; Lee, Young Hyuk; Ko, Kyung Og; Lim, Jae Woo; Cheon, Eun Jung; Lee, Gyung Min

    2016-01-01

    Purpose We sought to examine the relationship between the clinical manifestations of nonspecific reactive hepatitis and respiratory virus infection in pediatric patients. Methods Patients admitted to the pediatric unit of Konyang University Hospital for lower respiratory tract disease between January 1, 2014 and December 31, 2014 and who underwent reverse transcriptase polymerase chain reaction tests were examined. The patients were divided into those with increased levels of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) and those with normal ALT or AST levels. Further, patients with increased ALT and AST levels were individually compared with patients in the normal group, and the blood test results were compared according to the type of respiratory virus. Results Patients with increased ALT or AST levels had one more day of hospital stay, on average, compared with patients in the normal group (5.3±3.1 days vs. 4.4±3.0 days, p=0.019). Patients in the increased ALT level group were younger and had a longer mean hospital stay, compared with patients in the normal group (p=0.022 and 0.003, respectively). The incidences of increased ALT or AST were the highest in adenovirus infections (6/24, 25.0%), followed by enterovirus (2/11, 18.2%) and respiratory syncytial virus A (21/131, 16.0%) infections. Conclusion Nonspecific reactive hepatitis is more common among patients with adenovirus, enterovirus and respiratory syncytial virus infection, as well as among those infected at a younger age. Compared with AST levels, ALT levels are better indicators of the severity of nonspecific reactive hepatitis. PMID:28090469

  18. Immune thrombocytopenic purpura might be an early hematologic manifestation of undiagnosed human immunodeficiency virus infection.

    PubMed

    Lai, Shih-Wei; Lin, Hsien-Feng; Lin, Cheng-Li; Liao, Kuan-Fu

    2017-03-01

    Little research focuses on the association between immune thrombocytopenic purpura and human immunodeficiency virus infection in Taiwan. This study investigated whether immune thrombocytopenic purpura might be an early hematologic manifestation of undiagnosed human immunodeficiency virus infection in Taiwan. We conducted a retrospective population-based cohort study using data of individuals enrolled in Taiwan National Health Insurance Program. There were 5472 subjects aged 1-84 years with a new diagnosis of immune thrombocytopenic purpura as the purpura group since 1998-2010 and 21,887 sex-matched and age-matched, randomly selected subjects without immune thrombocytopenic purpura as the non-purpura group. The incidence of human immunodeficiency virus infection at the end of 2011 was measured in both groups. We used the multivariable Cox proportional hazards regression model to measure the hazard ratio and 95 % confidence interval (CI) for the association between immune thrombocytopenic purpura and human immunodeficiency virus infection. The overall incidence of human immunodeficiency virus infection was 6.47-fold higher in the purpura group than that in the non-purpura group (3.78 vs. 0.58 per 10,000 person-years, 95 % CI 5.83-7.18). After controlling for potential confounding factors, the adjusted HR of human immunodeficiency virus infection was 6.3 (95 % CI 2.58-15.4) for the purpura group, as compared with the non-purpura group. We conclude that individuals with immune thrombocytopenic purpura are 6.47-fold more likely to have human immunodeficiency virus infection than those without immune thrombocytopenic purpura. We suggest not all patients, but only those who have risk factors for human immunodeficiency virus infection should receive testing for undiagnosed human immunodeficiency virus infection when they develop immune thrombocytopenic purpura.

  19. [Hashimoto encephalitis and depression].

    PubMed

    Veltman, E M; Rhebergen, D; van Exel, E; Stek, M L

    2015-01-01

    Hashimoto encephalitis (he) is an auto-immune disease, with 40-50% of patients developing psychopathology. This could require targeted treatment. HE and prednison could both cloud the identification of a concurrent depressive disorder. We saw a 78-year-old woman with he and a severe depression, and treated her succesfully with ect.

  20. Parainfluenza Virus 5 Expressing the G Protein of Rabies Virus Protects Mice after Rabies Virus Infection

    PubMed Central

    Huang, Ying; Chen, Zhenhai; Huang, Junhua

    2014-01-01

    Rabies remains a major public health threat around the world. Once symptoms appear, there is no effective treatment to prevent death. In this work, we tested a recombinant parainfluenza virus 5 (PIV5) strain expressing the glycoprotein (G) of rabies (PIV5-G) as a therapy for rabies virus infection: we have found that PIV5-G protected mice as late as 6 days after rabies virus infection. PIV5-G is a promising vaccine for prevention and treatment of rabies virus infection. PMID:25552723

  1. Diversity of Viruses Infecting the Green Microalga Ostreococcus lucimarinus

    PubMed Central

    Derelle, Evelyne; Monier, Adam; Cooke, Richard; Worden, Alexandra Z.

    2015-01-01

    ABSTRACT The functional diversity of eukaryotic viruses infecting a single host strain from seawater samples originating from distant marine locations is unknown. To estimate this diversity, we used lysis plaque assays to detect viruses that infect the widespread species Ostreococcus lucimarinus, which is found in coastal and mesotrophic systems, and O. tauri, which was isolated from coastal and lagoon sites from the northwest Mediterranean Sea. Detection of viral lytic activities against O. tauri was not observed using seawater from most sites, except those close to the area where the host strain was isolated. In contrast, the more cosmopolitan O. lucimarinus species recovered viruses from locations in the Atlantic and Pacific Oceans and the Mediterranean Sea. Six new O. lucimarinus viruses (OlVs) then were characterized and their genomes sequenced. Two subgroups of OlVs were distinguished based on their genetic distances and on the inversion of a central 32-kb-long DNA fragment, but overall their genomes displayed a high level of synteny. The two groups did not correspond to proximity of isolation sites, and the phylogenetic distance between these subgroups was higher than the distances observed among viruses infecting O. tauri. Our study demonstrates that viruses originating from very distant sites are able to infect the same algal host strain and can be more diverse than those infecting different species of the same genus. Finally, distinctive features and evolutionary distances between these different viral subgroups does not appear to be linked to biogeography of the viral isolates. IMPORTANCE Marine eukaryotic phytoplankton virus diversity has yet to be addressed, and more specifically, it is unclear whether diversity is connected to geographical distance and whether differential infection and lysis patterns exist among such viruses that infect the same host strain. Here, we assessed the genetic distance of geographically segregated viruses that infect the

  2. Seroepidemiology of Asymptomatic Dengue Virus Infection in Jeddah, Saudi Arabia

    PubMed Central

    Jamjoom, Ghazi A.; Azhar, Esam I.; Kao, Moujahid A.; Radadi, Raja M.

    2016-01-01

    BACKGROUND Although virologically confirmed dengue fever has been recognized in Jeddah, Saudi Arabia, since 1994, causing yearly outbreaks, no proper seroepidemiologic studies on dengue virus have been conducted in this region. Such studies can define the extent of infection by this virus and estimate the proportion that may result in disease. The aim of this study was to measure the seroprevalence of past dengue virus infection in healthy Saudi nationals from different areas in the city of Jeddah and to investigate demographic and environmental factors that may increase exposure to infection. METHODS Sera were collected from 1984 Saudi subjects attending primary health care centers in six districts of Jeddah. These included general patients of various ages seeking routine vaccinations, antenatal care or treatment of different illnesses excluding fever or suspected dengue. A number of blood donors were also tested. Serum samples were tested by enzyme immunoassay (EIA) for IgG antibodies to dengue viruses 1, 2, 3, 4. A questionnaire was completed for each patient recording various anthropometric data and factors that may indicate possible risk of exposure to mosquito bites and dengue infection. Patients with missing data and those who reported a history of dengue fever were excluded from analysis, resulting in a sample of 1939 patients to be analyzed. RESULTS The overall prevalence of dengue virus infection as measured by anti-dengue IgG antibodies from asymptomatic residents in Jeddah was 47.8% (927/1939) and 37% (68/184) in blood donors. Infection mostly did not result in recognizable disease, as only 19 of 1956 subjects with complete information (0.1%) reported having dengue fever in the past. Anti dengue seropositivity increased with age and was higher in males than females and in residents of communal housing and multistory buildings than in villas. One of the six districts showed significant increase in exposure rate as compared to the others. Availability of

  3. Psoralen inactivation of influenza and herpes simplex viruses and of virus-infected cells.

    PubMed Central

    Redfield, D C; Richman, D D; Oxman, M N; Kronenberg, L H

    1981-01-01

    Psoralen compounds covalently bind to nucleic acids when irradiated with long-wavelength ultraviolet light. This treatment can destroy the infectivity of deoxyribonucleic acid and ribonucleic acid viruses. Two psoralen compounds, 4'-hydroxymethyltrioxsalen and 4'-aminomethyltrioxsalen, were used with long-wavelength ultraviolet light to inactivate cell-free herpes simplex and influenza viruses and to render virus-infected cells noninfectious. This method of inactivation was compared with germicidal (short-wavelength) ultraviolet light irradiation. The antigenicity of the treated, virus-infected, antigen-bearing cells was examined by immunofluorescence and radioimmunoassay and by measuring the capacity of the herpes simplex virus-infected cells to stimulate virus-specific lymphocyte proliferation. The infectivity of the virus-infected cells could be totally eliminated without altering their viral antigenicity. The use of psoralen plus long-wavelength ultraviolet light is well suited to the preparation of noninfectious virus antigens and virus antigen-bearing cells for immunological assays. PMID:6265375

  4. The Epigenetic Regulator G9a Mediates Tolerance to RNA Virus Infection in Drosophila

    PubMed Central

    Merkling, Sarah H.; Bronkhorst, Alfred W.; Kramer, Jamie M.; Overheul, Gijs J.; Schenck, Annette; Van Rij, Ronald P.

    2015-01-01

    Little is known about the tolerance mechanisms that reduce the negative effects of microbial infection on host fitness. Here, we demonstrate that the histone H3 lysine 9 methyltransferase G9a regulates tolerance to virus infection by shaping the response of the evolutionary conserved Jak-Stat pathway in Drosophila. G9a-deficient mutants are more sensitive to RNA virus infection and succumb faster to infection than wild-type controls, which was associated with strongly increased Jak-Stat dependent responses, but not with major differences in viral load. Genetic experiments indicate that hyperactivated Jak-Stat responses are associated with early lethality in virus-infected flies. Our results identify an essential epigenetic mechanism underlying tolerance to virus infection. PMID:25880195

  5. The mammalian response to virus infection is independent of small RNA silencing

    PubMed Central

    Backes, Simone; Langlois, Ryan A.; Schmid, Sonja; Varble, Andrew; Shim, Jaehee V.; Sachs, David

    2014-01-01

    Summary A successful cellular response to virus infection is essential for evolutionary survival. In plants, arthropods, and nematodes, cellular antiviral defenses rely on RNA interference (RNAi). Interestingly, the mammalian response to virus is predominantly orchestrated through interferon (IFN)-mediated induction of antiviral proteins. Despite the potency of the IFN system, it remains unclear whether mammals also have the capacity to employ antiviral RNAi. Here we investigate this by disabling either IFN, small RNA function or both activities in the context of virus infection. We find that loss of small RNAs in the context of an in vivo RNA virus infection lowers titers due to reduced transcriptional repression of the host antiviral response. In contrast, enabling a virus with the capacity to inhibit the IFN system results in increased titers. Taken together, we conclude that small RNA silencing is not a physiological contributor to the IFN-mediated cellular response to virus infection. PMID:24953656

  6. Psoralen inactivation of influenza and herpes simplex viruses and of virus-infected cells

    SciTech Connect

    Redfield, D.C.; Richman, D.D.; Oxman, M.N.; Kronenberg, L.H.

    1981-06-01

    Psoralen compounds covalently bind to nucleic acids when irradiated with long-wavelength ultraviolet light. This treatment can destroy the infectivity of deoxyribonucleic acid and ribonucleic acid viruses. Two psoralen compounds, 4'-hydroxymethyltrioxsalen and 4'-aminomethyltrioxsalen, were used with long-wavelength ultraviolet light to inactivate cell-free herpes simplex and influenza viruses and to render virus-infected cells noninfectious. This method of inactivation was compared with germicidal (short-wavelength) ultraviolet light irradiation. The antigenicity of the treated, virus-infected, antigen-bearing cells was examined by immunofluorescence and radioimmunoassay and by measuring the capacity of the herpes simplex virus-infected cells to stimulate virus-specific lymphocyte proliferation. The infectivity of the virus-infected cells could be totally eliminated without altering their viral antigenicity. The use of psoralen plus long-wavelength ultraviolet light is well suited to the preparation of noninfectious virus antigens and virus antigen-bearing cells for immunological assays.

  7. Necrolytic acral erythema: a rare skin disease associated with hepatitis C virus infection*

    PubMed Central

    Botelho, Luciane Francisca Fernandes; Enokihara, Milvia Maria Simões e Silva; Enokihara, Mauro Yoshiaki

    2016-01-01

    Necrolytic acral erythema is a rare skin disease associated with hepatitis C virus infection. We report a case of a 31-year-old woman with hepatitis C virus infection and decreased zinc serum level. Physical examination revealed scaly, lichenified plaques, well-demarcated with an erythematous peripheral rim located on the lower limbs. After blood transfusion and oral zinc supplementation the patient presented an improvement of lesions. PMID:27828642

  8. Zika virus infection complicated by Guillain-Barre syndrome--case report, French Polynesia, December 2013.

    PubMed

    Oehler, E; Watrin, L; Larre, P; Leparc-Goffart, I; Lastere, S; Valour, F; Baudouin, L; Mallet, Hp; Musso, D; Ghawche, F

    2014-03-06

    Zika fever, considered as an emerging disease of arboviral origin, because of its expanding geographic area, is known as a benign infection usually presenting as an influenza-like illness with cutaneous rash. So far, Zika virus infection has never led to hospitalisation. We describe the first case of Guillain-Barré syndrome (GBS) occurring immediately after a Zika virus infection, during the current Zika and type 1 and 3 dengue fever co-epidemics in French Polynesia.

  9. Zika virus infection spread through saliva--a truth or myth?

    PubMed

    Siqueira, Walter Luiz; Moffa, Eduardo Buozi; Mussi, Maria Carolina Martins; Machado, Maria Aparecida de Andrade Moreira

    2016-01-01

    In this Point-of-view article we highlighted some features related to saliva and virus infection, in special for zika virus. In addition, we pointed out the potential oral problems caused by a microcephaly originated by a zika virus infection. In the end the, we demonstrated the importance of a more comprehensive exploration of saliva and their components as a fluid for diagnostic and therapeutic approaches on oral and systemic diseases.

  10. Preparation and efficacy of an inactivated subunit vaccine (NFUIBHK) against type 2 Herpes simplex virus infection.

    PubMed

    Skinner, G R; Williams, D R; Buchan, A; Whitney, J; Harding, M; Bodfish, K

    1978-11-17

    A vaccine against Herpes simplex virus infection was prepared by Nonidet NP 40 and formalin treatment of a type 1, infected-cell extract; virus particles were removed by ultracentrifugation over sucrose. These procedures were not detrimental to the antigenic quality of the vaccine preparation. The vaccine afforded significant protection to experimental type 2 genital herpes virus infection in mice, as adjudged by clinical observations, cytopathological change, and virus yields.

  11. Respiratory disease outbreak in a veterinary hospital associated with canine parainfluenza virus infection

    PubMed Central

    Weese, J. Scott; Stull, Jason

    2013-01-01

    A cluster of canine parainfluenza virus infections was identified in a veterinary referral hospital. While hospital-associated outbreaks of canine parainfluenza virus infection have not been previously reported, veterinary hospitals possess some of the same risk factors that may be present in traditional high-risk sites such as kennels. Hospital-associated transmission of canine respiratory pathogens, therefore, must be considered. PMID:23814307

  12. Does Zika virus infection affect mosquito response to repellents?

    PubMed

    Leal, Walter S; Barbosa, Rosângela M R; Zeng, Fangfang; Faierstein, Gabriel B; Tan, Kaiming; Paiva, Marcelo H S; Guedes, Duschinka R D; Crespo, Mônica M; Ayres, Constância F J

    2017-02-16

    The World Health Organization (WHO) recommends that people travelling to or living in areas with Zika virus (ZIKV) outbreaks or epidemics adopt prophylactic measures to reduce or eliminate mosquito bites, including the use of insect repellents. It is, however, unknown whether repellents are effective against ZIKV-infected mosquitoes, in part because of the ethical concerns related to exposing a human subject's arm to infected mosquitoes in the standard arm-in-cage assay. We used a previously developed, human subject-free behavioural assay, which mimics a human subject to evaluate the top two recommended insect repellents. Our measurements showed that DEET provided significantly higher protection than picaridin provided against noninfected, host-seeking females of the southern house mosquito, Culex quinquefasciatus, and the yellow fever mosquito, Aedes aegypti. When tested at lower doses, we observed a significant reduction in DEET-elicited protection against ZIKV-infected yellow fever mosquitoes from old and recent laboratory colonies. The reduction in protection is more likely associated with aging than the virus infection and could be compensated by applying a 5x higher dose of DEET. A substantial protection against ZIKV-infected and old noninfected mosquitoes was achieved with 5% DEET, which corresponds approximately to a 30% dose in the conventional arm-in-cage assays.

  13. [Epidemiology of hepatitis E virus infection in Spain].

    PubMed

    Echevarría, José Manuel; Fogeda, Marta; Avellón, Ana

    2015-04-01

    The general features of the epidemiology and ecology of hepatitis E virus in Spain are already known after 20 years of investigations. Genotype 3 strains, mainly from sub-genotype 3f, circulated among swine livestock and certain wild mammals, and would be sporadically transmitted to humans through direct contact with the reservoirs or by consumption of foods derived from them. Bivalve shellfish contaminated by hepatitis E virus from sewage could also play a role in transmission. Although the interpretation of results from seroprevalence studies in low endemic settings is still controversial, antibody to hepatitis E virus displays an overall prevalence less than 10% among the population of Spain, increasing significantly with age. From the, approximately, 150 cases of acute hepatitis E recorded in the international literature, males older than 40 years, suffering a mild, locally acquired disease predominate. In addition, hepatitis E might be more frequent in the North of the country than in other regions. Although the disease does not usually have a great clinical relevance, the occasional finding of cases of fulminant hepatitis, and of ribavirin-resistant, chronic hepatitis E virus infections among the immunocompromised would recommend the surveillance of the infection by the public health authority and a better implementation of specific diagnostic procedures in clinical laboratories.

  14. [Zika virus infection or the future of infectious diseases].

    PubMed

    Valerio Sallent, Lluís; Roure Díez, Sílvia; Fernández Rivas, Gema

    2016-10-07

    Zika virus belongs to the Flaviridae, an extended phylogenetic family containing dengue or yellow fever, viruses whose shared main vector are Aedes aegypti mosquitoes. The virus originally came from Central African simian reservoirs and, from there, expanded rapidly across the Pacific to South America. The disease is an example of exantematic fever usually mild. Mortality is very low and mainly limited to secondary Guillain-Barré or fetal microcephaly cases. Diagnostic confirmation requires a RT-PCR in blood up to the 5th day from the onset or in urine up to the 10-14th day. Specific IgM are identifiable from the 5th symptomatic day. Clinically, a suspected case should comply with: a) a journey to epidemic areas; b) a clinically compatible appearance with fever and skin rash, and c) a generally normal blood count/basic biochemistry. There is some evidence that causally relates Zika virus infection with fetal microcephaly. While waiting for definitive data, all pregnant women coming from Central or South America should be tested for Zika virus.

  15. Inhibition of Mayaro virus infection by bovine lactoferrin.

    PubMed

    Carvalho, Carlos A M; Sousa, Ivanildo P; Silva, Jerson L; Oliveira, Andréa C; Gonçalves, Rafael B; Gomes, Andre M O

    2014-03-01

    Mayaro virus (MAYV) is an arbovirus linked to several sporadic outbreaks of a highly debilitating febrile illness in many regions of South America. MAYV is on the verge of urbanization from the Amazon region and no effective antiviral intervention is available against human infections. Our aim was to investigate whether bovine lactoferrin (bLf), an iron-binding glycoprotein, could hinder MAYV infection. We show that bLf promotes a strong inhibition of virus infection with no cytotoxic effects. Monitoring the effect of bLf on different stages of infection, we observed that virus entry into the cell is the heavily compromised event. Moreover, we found that binding of bLf to the cell is highly dependent on the sulfation of glycosaminoglycans, suggesting that bLf impairs virus entry by blocking these molecules. Our findings highlight the antiviral potential of bLf and reveal an effective strategy against one of the major emerging human pathogens in the neotropics.

  16. Immunohistochemistry for the diagnosis of hepatitis E virus infection.

    PubMed

    Gupta, P; Jagya, N; Pabhu, S B; Durgapal, H; Acharya, S K; Panda, S K

    2012-02-01

    Hepatitis E virus (HEV) is an emerging pathogen and the most common cause of acute viral hepatitis all over the world. We describe here an immunohistochemical method for the detection of HEV antigens (pORF2 and pORF3) in formalin-fixed, paraffin-embedded liver tissues using monoclonal antibodies raised against two of the virus proteins (pORF2 and pORF3). We analysed their specificity and sensitivity in comparison with serology and nucleic acid detection in cases of acute liver failure (ALF). We used this test on 30 liver biopsies collected post-mortem from the patients of ALF caused by HEV infection. These cases were selected on the basis of positive results for enzyme immunoassay (IgM anti-HEV). Of the 30 cases taken from the archives of the Department of Pathology, the antibodies successfully stained all. However, only 25 serum samples (83.3%) of these were positive for HEV RNA. Fifteen controls used (Five noninfected liver tissues, five HBV- and five hepatitis C virus-infected liver tissues) were all negative. The immunohistochemical assay described here may prove a valuable tool for the detection of HEV infection in biopsy, autopsy and explant liver tissues and can serve as a link along with other available tests to delineate the extent of HEV-associated problem worldwide.

  17. Nasopharyngeal Protein Biomarkers of Acute Respiratory Virus Infection.

    PubMed

    Burke, Thomas W; Henao, Ricardo; Soderblom, Erik; Tsalik, Ephraim L; Thompson, J Will; McClain, Micah T; Nichols, Marshall; Nicholson, Bradly P; Veldman, Timothy; Lucas, Joseph E; Moseley, M Arthur; Turner, Ronald B; Lambkin-Williams, Robert; Hero, Alfred O; Woods, Christopher W; Ginsburg, Geoffrey S

    2017-02-21

    Infection of respiratory mucosa with viral pathogens triggers complex immunologic events in the affected host. We sought to characterize this response through proteomic analysis of nasopharyngeal lavage in human subjects experimentally challenged with influenza A/H3N2 or human rhinovirus, and to develop targeted assays measuring peptides involved in this host response allowing classification of acute respiratory virus infection. Unbiased proteomic discovery analysis identified 3285 peptides corresponding to 438 unique proteins, and revealed that infection with H3N2 induces significant alterations in protein expression. These include proteins involved in acute inflammatory response, innate immune response, and the complement cascade. These data provide insights into the nature of the biological response to viral infection of the upper respiratory tract, and the proteins that are dysregulated by viral infection form the basis of signature that accurately classifies the infected state. Verification of this signature using targeted mass spectrometry in independent cohorts of subjects challenged with influenza or rhinovirus demonstrates that it performs with high accuracy (0.8623 AUROC, 75% TPR, 97.46% TNR). With further development as a clinical diagnostic, this signature may have utility in rapid screening for emerging infections, avoidance of inappropriate antibacterial therapy, and more rapid implementation of appropriate therapeutic and public health strategies.

  18. Antibody-Dependent Enhancement of Marburg Virus Infection

    PubMed Central

    Nakayama, Eri; Tomabechi, Daisuke; Matsuno, Keita; Kishida, Noriko; Yoshida, Reiko; Feldmann, Heinz

    2011-01-01

    Background. Marburg virus (MARV) and Ebola virus (EBOV) cause severe hemorrhagic fever in primates. Earlier studies demonstrated that antibodies to particular epitopes on the glycoprotein (GP) of EBOV enhanced virus infectivity in vitro. Methods. To investigate this antibody-dependent enhancement (ADE) in MARV infection, we produced mouse antisera and monoclonal antibodies (mAbs) to the GPs of MARV strains Angola and Musoke. Results. The infectivity of vesicular stomatitis virus pseudotyped with Angola GP in K562 cells was significantly enhanced in the presence of Angola GP antisera, whereas only minimal ADE activity was seen with Musoke GP antisera. This difference correlated with the percentage of hybridoma clones producing infectivity-enhancing mAbs. Using mAbs to MARV GP, we identified 3 distinct ADE epitopes in the mucinlike region on Angola GP. Interestingly, some of these antibodies bound to both Angola and Musoke GPs but showed significantly higher ADE activity for strain Angola. ADE activity depended on epitopes in the mucinlike region and glycine at amino acid position 547, present in the Angola but absent in the Musoke GP. Conclusions. These results suggest a possible link between ADE and MARV pathogenicity and provide new insights into the mechanisms underlying ADE entry of filoviruses. PMID:21987779

  19. Inhibition of influenza A virus infection by ginsenosides

    PubMed Central

    Leon, Alberto J.; Kelvin, David J.

    2017-01-01

    Influenza viruses cause mild to severe respiratory infections in humans. Due to efficient means of transmission, the viruses infect human population on a large scale. Apart from vaccines, antiviral drugs are used to control infection; neuraminidase inhibitors are thought to be the first choice of treatment, particularly for severe cases. Rapidly evolving and emerging influenza viruses with increased frequency of viral resistance to these drugs stress the need to explore novel antiviral compounds. In this study, we investigated antiviral activity of ginseng extract and ginsenosides, the ginseng-derived triterpene and saponin compounds, against 2009 pandemic H1N1 virus in vitro and in vivo. Our data showed that treatment of mice with ginsenosides protected the animals from lethal 2009 pandemic H1N1 infection and lowered viral titers in animal lungs. Mechanistic studies revealed that ginsenosides interact with viral hemagglutinin protein and prevent the attachment of virus with α 2–3’ sialic acid receptors present on host cell surfaces. The interference in the viral attachment process subsequently minimizes viral entry into the cells and decreases the severity of the viral infection. We also describe that sugar moieties present in ginsenosides are indispensible for their attachment with viral HA protein. On the basis of our observations, we can say that ginsenosides are promising candidates for the development of antiviral drugs for influenza viruses. PMID:28187149

  20. Spatiotemporal Dynamics of Virus Infection Spreading in Tissues.

    PubMed

    Bocharov, Gennady; Meyerhans, Andreas; Bessonov, Nickolai; Trofimchuk, Sergei; Volpert, Vitaly

    2016-01-01

    Virus spreading in tissues is determined by virus transport, virus multiplication in host cells and the virus-induced immune response. Cytotoxic T cells remove infected cells with a rate determined by the infection level. The intensity of the immune response has a bell-shaped dependence on the concentration of virus, i.e., it increases at low and decays at high infection levels. A combination of these effects and a time delay in the immune response determine the development of virus infection in tissues like spleen or lymph nodes. The mathematical model described in this work consists of reaction-diffusion equations with a delay. It shows that the different regimes of infection spreading like the establishment of a low level infection, a high level infection or a transition between both are determined by the initial virus load and by the intensity of the immune response. The dynamics of the model solutions include simple and composed waves, and periodic and aperiodic oscillations. The results of analytical and numerical studies of the model provide a systematic basis for a quantitative understanding and interpretation of the determinants of the infection process in target organs and tissues from the image-derived data as well as of the spatiotemporal mechanisms of viral disease pathogenesis, and have direct implications for a biopsy-based medical testing of the chronic infection processes caused by viruses, e.g. HIV, HCV and HBV.

  1. A dual drug regimen synergistically blocks human parainfluenza virus infection

    NASA Astrophysics Data System (ADS)

    Bailly, Benjamin; Dirr, Larissa; El-Deeb, Ibrahim M.; Altmeyer, Ralf; Guillon, Patrice; von Itzstein, Mark

    2016-04-01

    Human parainfluenza type-3 virus (hPIV-3) is one of the principal aetiological agents of acute respiratory illness in infants worldwide and also shows high disease severity in the elderly and immunocompromised, but neither therapies nor vaccines are available to treat or prevent infection, respectively. Using a multidisciplinary approach we report herein that the approved drug suramin acts as a non-competitive in vitro inhibitor of the hPIV-3 haemagglutinin-neuraminidase (HN). Furthermore, the drug inhibits viral replication in mammalian epithelial cells with an IC50 of 30 μM, when applied post-adsorption. Significantly, we show in cell-based drug-combination studies using virus infection blockade assays, that suramin acts synergistically with the anti-influenza virus drug zanamivir. Our data suggests that lower concentrations of both drugs can be used to yield high levels of inhibition. Finally, using NMR spectroscopy and in silico docking simulations we confirmed that suramin binds HN simultaneously with zanamivir. This binding event occurs most likely in the vicinity of the protein primary binding site, resulting in an enhancement of the inhibitory potential of the N-acetylneuraminic acid-based inhibitor. This study offers a potentially exciting avenue for the treatment of parainfluenza infection by a combinatorial repurposing approach of well-established approved drugs.

  2. Epidemic polyarthritis (Ross River) virus infection in the Cook Islands.

    PubMed

    Rosen, L; Gubler, D J; Bennett, P H

    1981-11-01

    An epidemic of Ross River virus infection occurred in the Cook Islands early in 1980 and affected the majority of the inhabitants of Rarotonga, the most populated island in the group. This represents the easternmost extension of the virus which, until 1979, was believed limited to Australia, New Guinea, and the Solomon Islands. The clinical manifestations of Ross River disease, predominantly polyarthritis, did not differ significantly from those observed previously in Australia. However, unlike the experience in Australia, where Ross River virus has never been isolated from a patient with polyarthritis, the agent was recovered from the serum of one-half of approximately 100 such patients with serologically proven infections. It is not known if this latter observation is the result of a change in the virus, the different virus isolation technique employed, or other factors. It was found that the incubation period of the disease could be as short as 3 days--much less than previously suspected. Ross River virus was isolated from six pools of Aedes polynesiensis mosquitoes collected in nature and it appeared that this species was the most probable vector on Rarotonga. In view of the widespread distribution of Ae. polynesiensis on islands, in the eastern Pacific it would not be surprising if Ross River virus occurs in other previously unaffected areas in the future.

  3. Seronegative occult hepatitis C virus infection: clinical implications.

    PubMed

    Carreño, Vicente

    2014-11-01

    Occult hepatitis C virus infection (OCI) was first described in anti-HCV and serum HCV-RNA negative patients with abnormal values of liver enzymes but who presented HCV-RNA in liver and in peripheral blood mononuclear cells. Up to now, two types of OCI are recognized: seronegative OCI (anti-HCV and serum HCV-RNA negative) and seropositive OCI (anti-HCV positive and serum HCV-RNA negative). The concept of OCI is still a matter of debate, probably because both types of OCI are not considered as different entities. This review focuses on seronegative OCI. The existence of seronegative OCI has been documented all around the world with the implication of different HCV genotypes (1-4). Seronegative OCI is associated with cryptogenic chronic hepatitis and liver cirrhosis and it may be involved in the appearance of hepatocellular carcinoma. Also seronegative OCI may increase the histological liver damage in chronic hepatitis B and in HIV-infected patients. It may have a negative influence in the natural history of hemodialysis patients and in immune-mediated glomerulonephritis. Seronegative OCI has been detected also in patients with haematological diseases, among healthy subjects and in drug users. Other publications indicate the potential infectivity of seronegative OCI in the setting of family members, sexual partners and liver transplantation. In summary, seronegative OCI may play a role in liver diseases and other human pathologies and may be present in healthy people but larger studies are needed to confirm these findings.

  4. Emerging Zika Virus Infection: A Rapidly Evolving Situation.

    PubMed

    Bordi, Licia; Avsic-Zupanc, Tatjana; Lalle, Eleonora; Vairo, Francesco; Rosaria Capobianchi, Maria; da Costa Vasconcelos, Pedro Fernando

    2016-12-29

    Zika virus is a mosquito-borne flavivirus, firstly identified in Uganda and responsible for sporadic human cases in Africa and Asia until recently, when large outbreak occurred in Pacific Ocean and the Americas. Since the main vectors during its spread outside of Africa have been Ae. albopictus and Ae. aegypti mosquitoes, which are widely distributed all over the world, there is urgent need for a coordinated response for prevention and spread of ZIKV epidemics.Despite clinical manifestation of Zika virus infection are usually mild and self limiting, there are reports suggesting, during the recent epidemic, an association of ZIKV infection with severe consequences, including fetal/newborn microcephaly, due to vertical in utero transmission, autoimmune-neurological presentations including cranial nerve dysfunction, and Guillain-Barré Syndrome in adults. The primary mode of transmission of Zika virus between humans is through the bite of an infected female mosquito of the Aedes genus, but also sexual and blood transfusion transmission may occur. Moreover, a case of non-sexual spread from one person to another has been described, indicating that we still have more to learn about Zika transmission.Biological basis for pathogenetic effects are under investigation. Laboratory diagnosis is challenging since, so far, there are no "gold standard" diagnostic tools, and the low and short viremia in the acute phase, and together with the high cross-reactivity among the members of flavivirus genus are the most challenging aspects to be overcome.

  5. Activated mouse eosinophils protect against lethal respiratory virus infection.

    PubMed

    Percopo, Caroline M; Dyer, Kimberly D; Ochkur, Sergei I; Luo, Janice L; Fischer, Elizabeth R; Lee, James J; Lee, Nancy A; Domachowske, Joseph B; Rosenberg, Helene F

    2014-01-30

    Eosinophils are recruited to the airways as a prominent feature of the asthmatic inflammatory response where they are broadly perceived as promoting pathophysiology. Respiratory virus infections exacerbate established asthma; however, the role of eosinophils and the nature of their interactions with respiratory viruses remain uncertain. To explore these questions, we established acute infection with the rodent pneumovirus, pneumonia virus of mice (PVM), in 3 distinct mouse models of Th2 cytokine-driven asthmatic inflammation. We found that eosinophils recruited to the airways of otherwise naïve mice in response to Aspergillus fumigatus, but not ovalbumin sensitization and challenge, are activated by and degranulate specifically in response to PVM infection. Furthermore, we demonstrate that activated eosinophils from both Aspergillus antigen and cytokine-driven asthma models are profoundly antiviral and promote survival in response to an otherwise lethal PVM infection. Thus, although activated eosinophils within a Th2-polarized inflammatory response may have pathophysiologic features, they are also efficient and effective mediators of antiviral host defense.

  6. Spatiotemporal Dynamics of Virus Infection Spreading in Tissues

    PubMed Central

    Meyerhans, Andreas; Bessonov, Nickolai; Trofimchuk, Sergei; Volpert, Vitaly

    2016-01-01

    Virus spreading in tissues is determined by virus transport, virus multiplication in host cells and the virus-induced immune response. Cytotoxic T cells remove infected cells with a rate determined by the infection level. The intensity of the immune response has a bell-shaped dependence on the concentration of virus, i.e., it increases at low and decays at high infection levels. A combination of these effects and a time delay in the immune response determine the development of virus infection in tissues like spleen or lymph nodes. The mathematical model described in this work consists of reaction-diffusion equations with a delay. It shows that the different regimes of infection spreading like the establishment of a low level infection, a high level infection or a transition between both are determined by the initial virus load and by the intensity of the immune response. The dynamics of the model solutions include simple and composed waves, and periodic and aperiodic oscillations. The results of analytical and numerical studies of the model provide a systematic basis for a quantitative understanding and interpretation of the determinants of the infection process in target organs and tissues from the image-derived data as well as of the spatiotemporal mechanisms of viral disease pathogenesis, and have direct implications for a biopsy-based medical testing of the chronic infection processes caused by viruses, e.g. HIV, HCV and HBV. PMID:27997613

  7. Does Zika virus infection affect mosquito response to repellents?

    PubMed Central

    Leal, Walter S.; Barbosa, Rosângela M. R.; Zeng, Fangfang; Faierstein, Gabriel B.; Tan, Kaiming; Paiva, Marcelo H. S.; Guedes, Duschinka R. D.; Crespo, Mônica M.; Ayres, Constância F. J.

    2017-01-01

    The World Health Organization (WHO) recommends that people travelling to or living in areas with Zika virus (ZIKV) outbreaks or epidemics adopt prophylactic measures to reduce or eliminate mosquito bites, including the use of insect repellents. It is, however, unknown whether repellents are effective against ZIKV-infected mosquitoes, in part because of the ethical concerns related to exposing a human subject’s arm to infected mosquitoes in the standard arm-in-cage assay. We used a previously developed, human subject-free behavioural assay, which mimics a human subject to evaluate the top two recommended insect repellents. Our measurements showed that DEET provided significantly higher protection than picaridin provided against noninfected, host-seeking females of the southern house mosquito, Culex quinquefasciatus, and the yellow fever mosquito, Aedes aegypti. When tested at lower doses, we observed a significant reduction in DEET-elicited protection against ZIKV-infected yellow fever mosquitoes from old and recent laboratory colonies. The reduction in protection is more likely associated with aging than the virus infection and could be compensated by applying a 5x higher dose of DEET. A substantial protection against ZIKV-infected and old noninfected mosquitoes was achieved with 5% DEET, which corresponds approximately to a 30% dose in the conventional arm-in-cage assays. PMID:28205633

  8. The role of shrimp miR-965 in virus infection.

    PubMed

    Shu, Le; Li, Changrun; Zhang, Xiaobo

    2016-07-01

    RNAi, mediated by microRNAs (miRNAs), has attracted increasing attention for its important role in cross-talk between host and virus. However, the role of host miRNA in the virus infection in vivo has not been intensively investigated. In this study, the effects of a shrimp miRNA (miR-965) on the white spot syndrome virus (WSSV) infection were characterized. The results indicated that the expression of miR-965 was significantly upregulated in shrimp in response to the WSSV challenge, suggesting its involvement in the virus infection. The miR-965 silencing led to significant increases of WSSV copies and virus-infected shrimp mortality, while the miR-965 overexpression resulted in the decreased WSSV copies and virus-infected shrimp mortality, indicating that miR-965 played a negative role in the WSSV infection. The further data revealed that miR-965 inhibited the virus infection by targeting the viral wsv240 gene, an important gene required for the WSSV infection in shrimp. The results demonstrated that miR-965 could promote the shrimp phagocytosis against virus infection by targeting the shrimp ATG5 (autophagy related 5) gene. Therefore, our findings presented novel evidence to better understand the anfractuous host-virus interactions in vivo.

  9. Role of Cytokines and Neurotrophins in the Central Nervous System in Venezuelan Equine Encephalitis Virus Pathogenesis

    DTIC Science & Technology

    2001-01-01

    including, but not limited to, Crohn s disease (63), atherosclerotic plaques (47), autoimmune encephalomyelitis (96), Japanese encephalitis (132), and...gene expression in astrocytes.................................................58 xi LIST OF ABBREVIATIONS AD Alzheimer s Disease AIDS Acquired Immune...Syndrome GDNF Glial cell-line derived neurotrophic factor HAM HTLV-Associated Myelopathy HD Huntington s Disease HIV Human Immunodeficiency Virus HTLV

  10. Role of Cytokines and Neurotrophins in the Central Nervous System in Venezuelan Equine Encephalitis Pathogenesis

    DTIC Science & Technology

    2001-03-21

    to, Crohn s disease (63), atherosclerotic plaques (47), autoimmune encephalomyelitis (96), Japanese encephalitis (132), and Venezuelan equine...astrocytes.................................................58 xi LIST OF ABBREVIATIONS AD Alzheimer s Disease AIDS Acquired Immune Deficiency Syndrome...line derived neurotrophic factor HAM HTLV-Associated Myelopathy HD Huntington s Disease HIV Human Immunodeficiency Virus HTLV Human T-Lymphotrophic

  11. Possible Zika Virus Infection Among Pregnant Women - United States and Territories, May 2016.

    PubMed

    Simeone, Regina M; Shapiro-Mendoza, Carrie K; Meaney-Delman, Dana; Petersen, Emily E; Galang, Romeo R; Oduyebo, Titilope; Rivera-Garcia, Brenda; Valencia-Prado, Miguel; Newsome, Kimberly B; Pérez-Padilla, Janice; Williams, Tonya R; Biggerstaff, Matthew; Jamieson, Denise J; Honein, Margaret A

    2016-05-27

    Zika virus is a cause of microcephaly and brain abnormalities (1), and it is the first known mosquito-borne infection to cause congenital anomalies in humans. The establishment of a comprehensive surveillance system to monitor pregnant women with Zika virus infection will provide data to further elucidate the full range of potential outcomes for fetuses and infants of mothers with asymptomatic and symptomatic Zika virus infection during pregnancy. In February 2016, Zika virus disease and congenital Zika virus infections became nationally notifiable conditions in the United States (2). Cases in pregnant women with laboratory evidence of Zika virus infection who have either 1) symptomatic infection or 2) asymptomatic infection with diagnosed complications of pregnancy can be reported as cases of Zika virus disease to ArboNET* (2), CDC's national arboviral diseases surveillance system. Under existing interim guidelines from the Council for State and Territorial Epidemiologists (CSTE), asymptomatic Zika virus infections in pregnant women who do not have known pregnancy complications are not reportable. ArboNET does not currently include pregnancy surveillance information (e.g., gestational age or pregnancy exposures) or pregnancy outcomes. To understand the full impact of infection on the fetus and neonate, other systems are needed for reporting and active monitoring of pregnant women with laboratory evidence of possible Zika virus infection during pregnancy. Thus, in collaboration with state, local, tribal, and territorial health departments, CDC established two surveillance systems to monitor pregnancies and congenital outcomes among women with laboratory evidence of Zika virus infection(†) in the United States and territories: 1) the U.S. Zika Pregnancy Registry (USZPR),(§) which monitors pregnant women residing in U.S. states and all U.S. territories except Puerto Rico, and 2) the Zika Active Pregnancy Surveillance System (ZAPSS), which monitors pregnant women

  12. [Clinical polymorphism in Epstein-Barr virus infection].

    PubMed

    Martínez Aguilar, N E; Guido Bayardo, R; Vargas Camaño, M E; Compañ Gonález, D; Ramírez Ojeda, H

    1997-01-01

    Several diseases was associated with Epstein Barr virus (EBV) infection. In the next three cases, the clinical course was unusual . Case I: Polyclonal hypergammaglobulinemia, female 47 years old, she had systemic lupus erythematosus and clinical data of infectious mononucleosis but she evolved to a polyclonal gammopathy with IgM predominantly against EBV. Case II: Demyelinating encephalitis, male, 32 years old with central neurological alterations, IgM antibodies against EBV and demyelinating lesion in magnetic resonance image in brain steam. Case III. Villous leukoplakia, male, 40 years old developed right tonsil tumor. He had IgM antibodies against EBV. The antiviral and immunomodulator treatment (specific for each case) done a satisfactory clinical response in the three patients.

  13. Treatment Effectiveness of Amantadine Against Dengue Virus Infection

    PubMed Central

    Lin, Chieh-Cheng; Chen, Wen-Ching

    2016-01-01

    Case series Patient: — Final Diagnosis: Dengue fever infection Symptoms: Bone pain • fever Medication: — Clinical Procedure: — Specialty: Infectious Diseases Objective: Unusual or unexpected effect of treatment Background: About 400 million cases of dengue, a mosquito-borne disease, are reported annually, but no drug is yet available for treatment. In 1988, at Feng Lin Clinic, Taiwan, we encountered about 10,000 cases and tested various drugs before confirming an antiviral effect of amantadine against dengue virus in vitro. After we administered amantadine to patients for 1–2 days, most achieved full remission. None experienced potentially life-threatening dengue hemorrhagic fever or dengue shock syndrome. Herein, we present 34 cases from recent clinical experience that show amantadine’s unusual effect against dengue virus infection. Case Report: We divided 34 patients with symptoms of dengue fever, confirmed by a screening test, into 3 groups: 6 Category 1 patients received amantadine at onset, 21 Category 2 patients received amantadine within 2–6 days, and 7 Contrast group patients received no amantadine because they visited other clinics or were admitted to a large hospital. When Category 1 patients were treated with amantadine 100 mg 3 times per day, all symptoms dramatically subsided within 1–2 days. In Category 2 patients, most symptoms diminished within 1–2 days after starting the same regimen. In the Contrast group, all symptoms persisted 7 days after onset. White blood cell and platelet counts in Category 1 and 2 patients recovered to normal range, but remained below low normal in the Contrast group. Conclusions: Amantadine is effective and should be given as soon as possible to stop the disease course if dengue fever is confirmed through screening or clinical signs and symptoms. A well-designed larger sample study is warranted to test this effectiveness. PMID:27920420

  14. Treatment Effectiveness of Amantadine Against Dengue Virus Infection.

    PubMed

    Lin, Chieh-Cheng; Chen, Wen-Ching

    2016-12-05

    BACKGROUND About 400 million cases of dengue, a mosquito-borne disease, are reported annually, but no drug is yet available for treatment. In 1988, at Feng Lin Clinic, Taiwan, we encountered about 10,000 cases and tested various drugs before confirming an antiviral effect of amantadine against dengue virus in vitro. After we administered amantadine to patients for 1-2 days, most achieved full remission. None experienced potentially life-threatening dengue hemorrhagic fever or dengue shock syndrome. Herein, we present 34 cases from recent clinical experience that show amantadine's unusual effect against dengue virus infection. CASE REPORT We divided 34 patients with symptoms of dengue fever, confirmed by a screening test, into 3 groups: 6 Category 1 patients received amantadine at onset, 21 Category 2 patients received amantadine within 2-6 days, and 7 Contrast group patients received no amantadine because they visited other clinics or were admitted to a large hospital. When Category 1 patients were treated with amantadine 100 mg 3 times per day, all symptoms dramatically subsided within 1-2 days. In Category 2 patients, most symptoms diminished within 1-2 days after starting the same regimen. In the Contrast group, all symptoms persisted 7 days after onset. White blood cell and platelet counts in Category 1 and 2 patients recovered to normal range, but remained below low normal in the Contrast group. CONCLUSIONS Amantadine is effective and should be given as soon as possible to stop the disease course if dengue fever is confirmed through screening or clinical signs and symptoms. A well-designed larger sample study is warranted to test this effectiveness.

  15. Symptomatic Respiratory Virus Infection and Chronic Lung Allograft Dysfunction

    PubMed Central

    Fisher, Cynthia E.; Preiksaitis, Carl M.; Lease, Erika D.; Edelman, Jeffrey; Kirby, Katharine A.; Leisenring, Wendy M.; Raghu, Ganesh; Boeckh, Michael; Limaye, Ajit P.

    2016-01-01

    Background. Chronic lung allograft dysfunction (CLAD) is a major cause of allograft loss post-lung transplantation. Prior studies have examined the association between respiratory virus infection (RVI) and CLAD were limited by older diagnostic techniques, study design, and case numbers. We examined the association between symptomatic RVI and CLAD using modern diagnostic techniques in a large contemporary cohort of lung transplant recipients (LTRs). Methods. We retrospectively assessed clinical variables including acute rejection, cytomegalovirus pneumonia, upper and lower RVI, and the primary endpoint of CLAD (determined by 2 independent reviewers) in 250 LTRs in a single university transplantation program. Univariate and multivariate Cox models were used to analyze the relationship between RVI and CLAD in a time-dependent manner, incorporating different periods of risk following RVI diagnosis. Results. Fifty patients (20%) were diagnosed with CLAD at a median of 95 weeks post-transplantation, and 79 (32%) had 114 episodes of RVI. In multivariate analysis, rejection and RVI were independently associated with CLAD (adjusted hazard ratio [95% confidence interval]) 2.2 (1.2–3.9), P = .01 and 1.9 (1.1–3.5), P = .03, respectively. The association of RVI with CLAD was stronger the more proximate the RVI episode: 4.8 (1.9–11.6), P < .01; 3.4 (1.5–7.5), P < .01; and 2.4 (1.2–5.0), P = .02 in multivariate analysis for 3, 6, and 12 months following RVI, respectively. Conclusions. Symptomatic RVI is independently associated with development of CLAD, with increased risk at shorter time periods following RVI. Prospective studies to characterize the virologic determinants of CLAD and define the underlying mechanisms are warranted. PMID:26565010

  16. Antiretroviral therapy reduces neurodegeneration in human immunodeficiency virus infection

    PubMed Central

    Bryant, Alex K.; Ellis, Ronald J.; Umlauf, Anya; Gouaux, Ben; Soontornniyomkij, Virawudh; Letendre, Scott L.; Achim, Cristian L.; Masliah, Eliezer; Grant, Igor; Moore, David J.

    2015-01-01

    Objective To determine the effect of virally-suppressive antiretroviral therapy on cortical neurodegeneration and associated neurocognitive impairment. Design Retrospective, postmortem observational study. Methods Clinical neuropsychological and postmortem neuropathology data were analyzed in 90 human immunodeficiency virus-infected volunteers from the general community who had never undergone antiretroviral therapy (n=7, “naïve”) or who had undergone antiretroviral therapy and whose plasma viral load was detectable (n = 64 “unsuppressed”) or undetectable (n = 19, “suppressed”) at the last clinical visit prior to death. Subjects were predominately male (74/90, 82%) with a mean age of 44.7 years (SD 9.8). Cortical neurodegeneration was quantified by measuring microtubule-associated protein (MAP2) and synaptophysin (SYP) density in midfrontal cortex tissue sections. Results The suppressed group had higher SYP density than the naïve group (p = 0.007) and higher MAP2 density than the unsuppressed group (p = 0.04). The suppressed group had lower odds of human immunodeficiency virus-associated neurocognitive disorders than naïve (OR 0.07, p = 0.03). Higher SYP was associated with lower likelihood of human immunodeficiency virus-associated neurocognitive disorders in univariable (OR 0.8, p=0.03) and multivariable models after controlling for antiretroviral treatment and brain human immunodeficiency virus p24 protein levels (OR 0.72, p=0.01). Conclusions We conclude that virally suppressive antiretroviral treatment protects against cortical neurodegeneration. Further, we find evidence supporting the causal chain from treatment-mediated peripheral and central nervous system viral load suppression to reduced neurodegeneration and improved neurocognitive outcomes. PMID:25686681

  17. Influenza A virus infections in marine mammals and terrestrial carnivores.

    PubMed

    Harder, Timm C; Siebert, Ursula; Wohlsein, Peter; Vahlenkamp, Thomas

    2013-01-01

    Influenza A viruses (IAV), members of the Orthomyxoviridae, cover a wide host spectrum comprising a plethora of avian and, in comparison, a few mammalian species. The viral reservoir and gene pool are kept in metapopulations of aquatic wild birds. The mammalian-adapted IAVs originally arose by transspecies transmission from avian sources. In swine, horse and man, species-adapted IAV lineages circulate independently of the avian reservoir and cause predominantly respiratory disease of highly variable severity. Sporadic outbreaks of IAV infections associated with pneumonic clinical signs have repeatedly occurred in marine mammals (harbour seals [Phoca vitulina]) off the New England coast of the U.S.A. due to episodic transmission of avian IAV. However, no indigenous marine mammal IAV lineages are described. In contrast to marine mammals, avian- and equine-derived IAVs have formed stable circulating lineages in terrestrial carnivores: IAVs of subtype H3N2 and H3N8 are found in canine populations in South Korea, China, and the U.S.A. Experimental infections revealed that dogs and cats can be infected with an even wider range of avian IAVs. Cats, in particular, also proved susceptible to native infection with human pandemic H1N1 viruses and, according to serological data, may be vulnerable to infection with further human-adapted IAVs. Ferrets are susceptible to a variety of avian and mammalian IAVs and are an established animal model of human IAV infection. Thus, a potential role of pet cats, dogs and ferrets as mediators of avian-derived viruses to the human population does exist. A closer observation for influenza virus infections and transmissions at this animal-human interface is indicated.

  18. IL-27 Limits Type 2 Immunopathology Following Parainfluenza Virus Infection

    PubMed Central

    Wagage, Sagie; Sun, Yan; Christian, David A.; Harms Pritchard, Gretchen; Fang, Qun; Buza, Elizabeth L.; Jain, Deepika; Elloso, M. Merle; López, Carolina B.; Hunter, Christopher A.

    2017-01-01

    Respiratory paramyxoviruses are important causes of morbidity and mortality, particularly of infants and the elderly. In humans, a T helper (Th)2-biased immune response to these infections is associated with increased disease severity; however, little is known about the endogenous regulators of these responses that may be manipulated to ameliorate pathology. IL-27, a cytokine that regulates Th2 responses, is produced in the lungs during parainfluenza infection, but its role in disease pathogenesis is unknown. To determine whether IL-27 limits the development of pathogenic Th2 responses during paramyxovirus infection, IL-27-deficient or control mice were infected with the murine parainfluenza virus Sendai virus (SeV). Infected IL-27-deficient mice experienced increased weight loss, more severe lung lesions, and decreased survival compared to controls. IL-27 deficiency led to increased pulmonary eosinophils, alternatively activated macrophages (AAMs), and the emergence of Th2 responses. In control mice, IL-27 induced a population of IFN-γ+/IL-10+ CD4+ T cells that was replaced by IFN-γ+/IL-17+ and IFN-γ+/IL-13+ CD4+ T cells in IL-27-deficient mice. CD4+ T cell depletion in IL-27-deficient mice attenuated weight loss and decreased AAMs. Elimination of STAT6 signaling in IL-27-deficient mice reduced Th2 responses and decreased disease severity. These data indicate that endogenous IL-27 limits pathology during parainfluenza virus infection by regulating the quality of CD4+ T cell responses and therefore may have therapeutic potential in paramyxovirus infections. PMID:28129374

  19. Early pathogenesis of transmucosal feline immunodeficiency virus infection.

    PubMed

    Obert, Leslie A; Hoover, Edward A

    2002-06-01

    To identify the early target cells and tissues in transmucosal feline immunodeficiency virus (FIV) infection, cats were exposed to a clade C FIV isolate via the oral-nasal or vaginal mucosa and multiple tissues were examined by virus isolation coculture (VI), DNA PCR, catalyzed tyramide signal-amplified in situ hybridization (TSA-ISH), and immunohistochemistry between days 1 and 12 postinoculation (p.i.). FIV RNA was detected in tonsil and oral or vaginal mucosa as early as 1 day p.i. by TSA-ISH and in retropharyngeal, tracheobronchial, or external iliac lymph nodes and sometimes in spleen or blood mononuclear cells by day 2, indicating that regional and distant spread of virus-infected cells occurred rapidly after mucosal exposure. By day 8, viral RNA, DNA, and culturable virus were uniformly detected in regional and distant tissues, connoting systemic infection. TSA-ISH proved more sensitive than DNA PCR in detecting early FIV-infected cells. In mucosal tissues, the earliest demonstrable FIV-bearing cells were either within or subjacent to the mucosal epithelium or were in germinal centers of regional lymph nodes. The FIV(+) cells were of either of two morphological types, large stellate or small round. Those FIV RNA(+) cells which could be colabeled for a phenotype marker, were labeled for either dendritic-cell-associated protein p55 or T-lymphocyte receptor antigen CD3. These studies indicate that FIV crosses mucous membranes within hours after exposure and rapidly traffics via dendritic and T cells to systemic lymphoid tissues, a pathway similar to that thought to occur in the initial phase of infection by the human and simian immunodeficiency viruses.

  20. Invariant NKT Cell Response to Dengue Virus Infection in Human

    PubMed Central

    Matangkasombut, Ponpan; Chan-in, Wilawan; Opasawaschai, Anunya; Pongchaikul, Pisut; Tangthawornchaikul, Nattaya; Vasanawathana, Sirijitt; Limpitikul, Wannee; Malasit, Prida; Duangchinda, Thaneeya; Screaton, Gavin; Mongkolsapaya, Juthathip

    2014-01-01

    Background Dengue viral infection is a global health threat without vaccine or specific treatment. The clinical outcome varies from asymptomatic, mild dengue fever (DF) to severe dengue hemorrhagic fever (DHF). While adaptive immune responses were found to be detrimental in the dengue pathogenesis, the roles of earlier innate events remain largely uninvestigated. Invariant natural killer T (iNKT) cells represent innate-like T cells that could dictate subsequent adaptive response but their role in human dengue virus infection is not known. We hypothesized that iNKT cells play a role in human dengue infection. Methods Blood samples from a well-characterized cohort of children with DF, DHF, in comparison to non-dengue febrile illness (OFI) and healthy controls at various time points were studied. iNKT cells activation were analyzed by the expression of CD69 by flow cytometry. Their cytokine production was then analyzed after α-GalCer stimulation. Further, the CD1d expression on monocytes, and CD69 expression on conventional T cells were measured. Results iNKT cells were activated during acute dengue infection. The level of iNKT cell activation associates with the disease severity. Furthermore, these iNKT cells had altered functional response to subsequent ex vivo stimulation with α-GalCer. Moreover, during acute dengue infection, monocytic CD1d expression was also upregulated and conventional T cells also became activated. Conclusion iNKT cells might play an early and critical role in the pathogenesis of severe dengue viral infection in human. Targeting iNKT cells and CD1d serve as a potential therapeutic strategy for severe dengue infection in the future. PMID:24945350

  1. Occult hepatitis B virus infection: clinical implications in tuberculosis treatment.

    PubMed

    Trigo, C; do Brasil, P E A A; Costa, M J M; de Castro, L

    2016-12-01

    Occult hepatitis B virus infection (OBI) is characterized by the absence of HBsAg and persistence of the virus genome (HBV-DNA) in liver tissue and/or blood. OBI has been reported in several clinical contexts. However, the clinical significance of OBI in tuberculosis (TB) treatment is unknown. We investigated the OBI prevalence and its impact on the risk of drug-induced liver injury (DILI) during TB treatment. This was a prospective cohort study with one hundred patients who were treated for TB from 2008 to 2015. Laboratory, clinical and demographic data of TB patients were extracted from medical records. Based on HBV-DNA testing of serum samples, an OBI prevalence of 12% was established; almost half of these patients had both anti-HBc and anti-HBs serological markers. Low CD4(+) cell counts have been shown to be a risk factor for OBI among TB patients co-infected with HIV (P=.036). High DILI incidence was observed in this study. A multivariable Cox proportional hazard model was conducted and identified OBI (HR 2.98, 95% CI 1.30-6.86) as the strongest predictor for DILI when adjusted to CD4(+) cell count (HR 0.38, 95% CI 0.17-0.90), ALT before TB treatment (HR 1.37, 95% CI 0.81-2.32) and TB extrapulmonary clinical form (HR 2.91, 95% CI 1.75-7.21). The main aim of this study was to highlight DILI as a clinical outcome during treatment of TB patients with OBI. Therefore, HBV-DNA testing should be considered routinely in monitoring DILI, and also in other clinical implications associated with OBI, reduce morbidity and mortality.

  2. Inhibitory effects of carbocisteine on type A seasonal influenza virus infection in human airway epithelial cells.

    PubMed

    Yamaya, Mutsuo; Nishimura, Hidekazu; Shinya, Kyoko; Hatachi, Yukimasa; Sasaki, Takahiko; Yasuda, Hiroyasu; Yoshida, Motoki; Asada, Masanori; Fujino, Naoya; Suzuki, Takaya; Deng, Xue; Kubo, Hiroshi; Nagatomi, Ryoichi

    2010-08-01

    Type A human seasonal influenza (FluA) virus infection causes exacerbations of bronchial asthma and chronic obstructive pulmonary disease (COPD). l-carbocisteine, a mucolytic agent, reduces the frequency of common colds and exacerbations in COPD. However, the inhibitory effects of l-carbocisteine on FluA virus infection are uncertain. We studied the effects of l-carbocisteine on FluA virus infection in airway epithelial cells. Human tracheal epithelial cells were pretreated with l-carbocisteine and infected with FluA virus (H(3)N(2)). Viral titers in supernatant fluids, RNA of FluA virus in the cells, and concentrations of proinflammatory cytokines in supernatant fluids, including IL-6, increased with time after infection. l-carbocisteine reduced viral titers in supernatant fluids, RNA of FluA virus in the cells, the susceptibility to FluA virus infection, and concentrations of cytokines induced by virus infection. The epithelial cells expressed sialic acid with an alpha2,6-linkage (SAalpha2,6Gal), a receptor for human influenza virus on the cells, and l-carbocisteine reduced the expression of SAalpha2,6Gal. l-carbocisteine reduced the number of acidic endosomes from which FluA viral RNA enters into the cytoplasm and reduced the fluorescence intensity from acidic endosomes. Furthermore, l-carbocisteine reduced NF-kappaB proteins including p50 and p65 in the nuclear extracts of the cells. These findings suggest that l-carbocisteine may inhibit FluA virus infection, partly through the reduced expression of the receptor for human influenza virus in the human airway epithelial cells via the inhibition of NF-kappaB and through increasing pH in endosomes. l-carbocisteine may reduce airway inflammation in influenza virus infection.

  3. [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.

  4. Diagnosis of Oropouche Virus Infection Using a Recombinant Nucleocapsid Protein-Based Enzyme Immunoassay

    PubMed Central

    Saeed, Mohammad F.; Nunes, Marcio; Vasconcelos, Pedro F.; Travassos Da Rosa, Amelia P. A.; Watts, Douglas M.; Russell, Kevin; Shope, Robert E.; Tesh, Robert B.; Barrett, Alan D. T.

    2001-01-01

    Oropouche (ORO) virus is an emerging infectious agent that has caused numerous outbreaks of an acute febrile (dengue-like) illness among humans in Brazil, Peru, and Panama. Diagnosis of ORO virus infection is based mainly on serology. Two different antigens, hamster serum antigen (HSA) and Vero cell lysate antigen (VCLA), are currently used in enzyme immunoassays (EIAs) in Brazil and Peru, respectively, to investigate the epidemiology of ORO virus infection. Both antigens involve use of infectious virus, and for this reason their use is restricted. Consequently, the frequency and distribution of ORO virus infection are largely unexplored in other countries of South America. This report describes the use of a bacterially expressed recombinant nucleocapsid (rN) protein of ORO virus in EIAs for the diagnosis of ORO virus infection. The data revealed that the purified rN protein is comparable to the authentic viral N protein in its antigenic characteristics and is highly sensitive and specific in EIAs. Among 183 serum samples tested, a high degree of concordance was found between rN protein-based EIA and HSA- and VCLA-based EIAs for the detection of both ORO virus-specific immunoglobulin M (IgM) and IgG antibodies. The high sensitivity, specificity, and safety of the rN protein-based EIA make it a useful diagnostic technique that can be widely used to detect ORO virus infection in South America. PMID:11427552

  5. Transcriptional Profiling of the Immune Response to Marburg Virus Infection

    PubMed Central

    Yen, Judy; Caballero, Ignacio S.; Garamszegi, Sara; Malhotra, Shikha; Lin, Kenny; Hensley, Lisa; Goff, Arthur J.

    2015-01-01

    ABSTRACT Marburg virus is a genetically simple RNA virus that causes a severe hemorrhagic fever in humans and nonhuman primates. The mechanism of pathogenesis of the infection is not well understood, but it is well accepted that pathogenesis is appreciably driven by a hyperactive immune response. To better understand the overall response to Marburg virus challenge, we undertook a transcriptomic analysis of immune cells circulating in the blood following aerosol exposure of rhesus macaques to a lethal dose of Marburg virus. Using two-color microarrays, we analyzed the transcriptomes of peripheral blood mononuclear cells that were collected throughout the course of infection from 1 to 9 days postexposure, representing the full course of the infection. The response followed a 3-stage induction (early infection, 1 to 3 days postexposure; midinfection, 5 days postexposure; late infection, 7 to 9 days postexposure) that was led by a robust innate immune response. The host response to aerosolized Marburg virus was evident at 1 day postexposure. Analysis of cytokine transcripts that were overexpressed during infection indicated that previously unanalyzed cytokines are likely induced in response to exposure to Marburg virus and further suggested that the early immune response is skewed toward a Th2 response that would hamper the development of an effective antiviral immune response early in disease. Late infection events included the upregulation of coagulation-associated factors. These findings demonstrate very early host responses to Marburg virus infection and provide a rich data set for identification of factors expressed throughout the course of infection that can be investigated as markers of infection and targets for therapy. IMPORTANCE Marburg virus causes a severe infection that is associated with high mortality and hemorrhage. The disease is associated with an immune response that contributes to the lethality of the disease. In this study, we investigated how the

  6. Callithrix penicillata: a feasible experimental model for dengue virus infection.

    PubMed

    Ferreira, Milene Silveira; de Castro, Paulo Henrique Gomes; Silva, Gilmara Abreu; Casseb, Samir Mansur Moraes; Dias Júnior, Antônio Gregório; Rodrigues, Sueli Guerreiros; Azevedo, Raimunda do Socorro da Silva; Costa e Silva, Matheus Fernandes; Zauli, Danielle Alves Gomes; Araújo, Márcio Sobreira Silva; Béla, Samantha Ribeiro; Teixeira-Carvalho, Andréa; Martins-Filho, Olindo Assis; Vasconcelos, Pedro Fernando da Costa

    2014-01-01

    , a protective axes TNF-alpha/Lymphocytes/Platelets, and a pathological IL-2/IL-6/Viremia/Monocyte/PT bond. Later on, the biomarker network highlighted the interaction IFN-gamma/PLT/DENV-3(IgM;HAI)/PT, and the involvement of type-2 cytokines (IL-4; IL-5). Our findings demonstrated that C. penicillata is a feasible experimental model for dengue virus infection, which could be useful to pathogenesis studies, discovery of novel antiviral drugs as well as to evaluate vaccine candidates against DENV.

  7. CONTRIBUTIONS TO THE PATHOLOGY OF EXPERIMENTAL VIRUS ENCEPHALITIS

    PubMed Central

    Flexner, Simon; Amoss, Harold L.

    1925-01-01

    rabbit. It is indeed highly probable that, in so far as such a virus has been found at all in the cerebrospinal fluid, it also is a specimen of the herpes virus. Our studies lead us to suppose that at best it is an infrequent event for the herpes virus to occur in demonstrable form in the cerebrospinal fluid. Perhaps a more delicate means of detection than the rabbit inoculation would serve to reveal the presence oftener. It is known that strains of herpes virus of greater or less intensity of action for rabbits exist. It is, of course, possible that we discover, by present methods, only the highly active strains and those only when chancing to be present in a certain concentration. We inoculated 100 specimens of cerebrospinal fluid and obtained in a single instance the virus infection of the rabbit. In all respects the J. B. virus agrees in intensity of effect, in mode of attack upon the cornea, skin, and brain, and in immunization responses, with the true strains of herpes virus and the so called strains of encephalitis virus. If, as the above statements indicate, all the virus strains of the class considered are examples of the herpes virus, it follows that the etiology of epidemic encephalitis remains entirely unresolved. It is highly improbable that the ubiquitous herpes virus plays the kind of part in human pathology which it has been shown to play in experimental rabbit pathology. While the active strains of that virus possess a strong affinity for the brain structures of the rabbit, the virus has not in the past shown any selective affinity for the brain of man. To ascribe epidemic encephalitis in man to particular and peculiar varieties of the herpes virus is, with our present knowledge, unwarranted.20 The wide variations in histological lesions described in the brain of rabbits succumbing to herpes or virus encephalitis raise the question of the essential manner of action of the virus upon the brain tissues. Hitherto it has been the cellular infiltrative

  8. Autoimmune NMDA receptor encephalitis.

    PubMed

    Lazar-Molnar, Eszter; Tebo, Anne E

    2015-01-01

    Anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis is a treatable autoimmune disease of the central nervous system (CNS) with prominent neurologic and psychiatric features at disease onset. The disease is associated with the production of autoantibodies to NMDAR, a protein involved in memory function and synaptic plasticity. Affected patients develop a multistage progressive illness with symptoms ranging from memory deficits, seizures and psychosis, to potentially lethal catatonia, and autonomic and breathing instability. The outcome can be much improved with accurate diagnosis and early treatment using adequate immunosuppressive therapy. However, since the neurological and psychiatric symptoms as well as the clinical examination results can be non-specific, the disease is probably under-recognized. Reliable and accurate clinical testing for the identification of NMDAR autoantibodies is crucial for diagnosis, timely treatment selection, and monitoring. Recently, a cell-based indirect immunofluorescent antibody test for the detection of IgG antibodies to NMDAR has become available for diagnostic use. This review highlights the progress and challenges of laboratory testing in the evaluation and management anti-NMDAR encephalitis, and perspectives for the future.

  9. Rift Valley Fever Virus Infection in Golden Syrian Hamsters

    PubMed Central

    Scharton, Dionna; Van Wettere, Arnaud J.; Bailey, Kevin W.; Vest, Zachary; Westover, Jonna B.; Siddharthan, Venkatraman; Gowen, Brian B.

    2015-01-01

    Rift Valley fever virus (RVFV) is a formidable pathogen that causes severe disease and abortion in a variety of livestock species and a range of disease in humans that includes hemorrhagic fever, fulminant hepatitis, encephalitis and blindness. The natural transmission cycle involves mosquito vectors, but exposure can also occur through contact with infected fluids and tissues. The lack of approved antiviral therapies and vaccines for human use underlies the importance of small animal models for proof-of-concept efficacy studies. Several mouse and rat models of RVFV infection have been well characterized and provide useful systems for the study of certain aspects of pathogenesis, as well as antiviral drug and vaccine development. However, certain host-directed therapeutics may not act on mouse or rat pathways. Here, we describe the natural history of disease in golden Syrian hamsters challenged subcutaneously with the pathogenic ZH501 strain of RVFV. Peracute disease resulted in rapid lethality within 2 to 3 days of RVFV challenge. High titer viremia and substantial viral loads were observed in most tissues examined; however, histopathology and immunostaining for RVFV antigen were largely restricted to the liver. Acute hepatocellular necrosis associated with a strong presence of viral antigen in the hepatocytes indicates that fulminant hepatitis is the likely cause of mortality. Further studies to assess the susceptibility and disease progression following respiratory route exposure are warranted. The use of the hamsters to model RVFV infection is suitable for early stage antiviral drug and vaccine development studies. PMID:25607955

  10. Rift Valley fever virus infection in golden Syrian hamsters.

    PubMed

    Scharton, Dionna; Van Wettere, Arnaud J; Bailey, Kevin W; Vest, Zachary; Westover, Jonna B; Siddharthan, Venkatraman; Gowen, Brian B

    2015-01-01

    Rift Valley fever virus (RVFV) is a formidable pathogen that causes severe disease and abortion in a variety of livestock species and a range of disease in humans that includes hemorrhagic fever, fulminant hepatitis, encephalitis and blindness. The natural transmission cycle involves mosquito vectors, but exposure can also occur through contact with infected fluids and tissues. The lack of approved antiviral therapies and vaccines for human use underlies the importance of small animal models for proof-of-concept efficacy studies. Several mouse and rat models of RVFV infection have been well characterized and provide useful systems for the study of certain aspects of pathogenesis, as well as antiviral drug and vaccine development. However, certain host-directed therapeutics may not act on mouse or rat pathways. Here, we describe the natural history of disease in golden Syrian hamsters challenged subcutaneously with the pathogenic ZH501 strain of RVFV. Peracute disease resulted in rapid lethality within 2 to 3 days of RVFV challenge. High titer viremia and substantial viral loads were observed in most tissues examined; however, histopathology and immunostaining for RVFV antigen were largely restricted to the liver. Acute hepatocellular necrosis associated with a strong presence of viral antigen in the hepatocytes indicates that fulminant hepatitis is the likely cause of mortality. Further studies to assess the susceptibility and disease progression following respiratory route exposure are warranted. The use of the hamsters to model RVFV infection is suitable for early stage antiviral drug and vaccine development studies.

  11. Innate immune responses in raccoons after raccoon rabies virus infection.

    PubMed

    Srithayakumar, Vythegi; Sribalachandran, Hariharan; Rosatte, Rick; Nadin-Davis, Susan A; Kyle, Christopher J

    2014-01-01

    Zoonotic wildlife diseases pose significant health risks not only to their primary vectors but also to humans and domestic animals. Rabies is a lethal encephalitis caused by rabies virus (RV). This RNA virus can infect a range of terrestrial mammals but each viral variant persists in a particular reservoir host. Active management of these host vectors is needed to minimize the negative impacts of this disease, and an understanding of the immune response to RV infection aids strategies for host vaccination. Current knowledge of immune responses to RV infection comes primarily from rodent models in which an innate immune response triggers activation of several genes and signalling pathways. It is unclear, however, how well rodent models represent the immune response of natural hosts. This study investigates the innate immune response of a primary host, the raccoon, to a peripheral challenge using the raccoon rabies virus (RRV). The extent and temporal course of this response during RRV infection was analysed using genes predicted to be upregulated during infection (IFNs; IFN regulatory factors; IL-6; Toll like receptor-3; TNF receptor). We found that RRV activated components of the innate immune system, with changes in levels of transcripts correlated with presence of viral RNA. Our results suggest that natural reservoirs of rabies may not mimic the immune response triggered in rodent models, highlighting the need for further studies of infection in primary hosts.

  12. Modeling Powassan virus infection in Peromyscus leucopus, a natural host

    PubMed Central

    Meade-White, Kimberly; Saturday, Greg; Scott, Dana; Bloom, Marshall E.

    2017-01-01

    The tick-borne flavivirus, Powassan virus (POWV) causes life-threatening encephalitis in humans in North America and Europe. POWV is transmitted by ixodid tick vectors that feed on small to medium-sized mammals, such as Peromyscus leucopus mice, which may serve as either reservoir, bridge or amplification hosts. Intraperitoneal and intracranial inoculation of 4-week old Peromyscus leucopus mice with 103 PFU of POWV did not result in overt clinical signs of disease. However, following intracranial inoculation, infected mice seroconverted to POWV and histopathological examinations revealed that the mice uniformly developed mild lymphocytic perivascular cuffing and microgliosis in the brain and spinal cord from 5 to 15 days post infection (dpi), suggesting an early inflammatory response. In contrast, intracranial inoculation of 4-week old C57BL/6 and BALB/c mice was lethal by 5 dpi. Intraperitoneal inoculation was lethal in BALB/c mice, but 40% (2/5) of C57BL/6 mice survived. We concluded that Peromyscus leucopus mice infected i.c. with a lethal dose of POWV support a limited infection, restricted to the central nervous system and mount an antibody response to the virus. However, they fail to develop clinical signs of disease and are able to control the infection. These results suggest the involvement of restriction factors, and the mechanism by which Peromyscus leucopus mice restrict POWV infection remains under study. PMID:28141800

  13. Impacts of allergic airway inflammation on lung pathology in a mouse model of influenza A virus infection

    PubMed Central

    Kawaguchi, Akira; Ohara, Yuki; Takahashi, Kenta; Sato, Yuko; Ainai, Akira; Nagata, Noriyo; Tashiro, Masato; Hasegawa, Hideki

    2017-01-01

    Influenza A virus is the respiratory pathogen responsible for influenza. Infection by the 2009 pandemic influenza A (H1N1) virus caused severe lower airway inflammation and pneumonia. Asthma is a chronic inflammatory disorder of the airways that affects the entire brachial tree, and was one of the commonest underlying medical conditions among patients hospitalized with the 2009 pandemic influenza virus infection. Although respiratory virus infections are the major causes of asthma exacerbation, the mechanism by which influenza exacerbates asthma is poorly understood. Animal models of disease comorbidity are crucial to understanding host-pathogen interactions and elucidating complex pathologies. Existing murine models of influenza virus infection in asthmatics show that asthmatic mice are highly resistant to influenza virus infection, which contradicts clinical observations in humans. Here, we developed a murine model of influenza virus/asthma comorbidity using NC/Nga mice, which are highly sensitive to allergic reactions such as atopic dermatitis and allergic airway inflammation. This model was then used to examine the impact of allergic airway inflammation on lung pathology in the 2009 pandemic influenza virus infected mice. The results showed that induction of acute allergic airway inflammation in pre-existing influenza virus infection had additive effects on exacerbation of lung pathology, which mirrors findings in human epidemiological studies. In contrast, pre-existing allergic airway inflammation protected from subsequent influenza virus infection, which was compatible with those of previous murine models of influenza virus infection in asthmatic mice. These variable outcomes of this murine model indicate that the temporal relation between allergic airway inflammation and influenza virus infection might play a critical role in asthma and influenza comorbidity. Thus, this murine model will further our understanding of how influenza virus infection affects an

  14. Hepatitis C virus infection with peripheral neuropathy is not always associated with cryoglobulinaemia

    PubMed Central

    Lidove, O; Cacoub, P; Maisonobe, T; Servan, J; Thibault, V; Piette, J; Leger, J

    2001-01-01

    OBJECTIVES—To describe cases of peripheral neuropathy associated with chronic hepatitis C virus infection without mixed cryoglobulinaemia.
METHODS—Four cases of peripheral neuropathy associated with chronic hepatitis C virus infection with persistent negativity of mixed cryoglobulinaemia were found.
RESULTS—All patients had small increases of transaminase levels and a positive viraemia. Liver biopsy showed chronic active hepatitis in all but one case (Knodell 4-9, Metavir A0F0-A3F3). Neuromuscular biopsy showed axonal neuropathy associated with lymphoid infiltrates around small vessels in two cases. Rheumatoid factor was always negative and C4 complement level was always normal. In three patients, neuropathy improved with interferon α, interferon α + ursodesoxycholic acid, or steroids + plasma exchange.
CONCLUSION—Peripheral neuropathy may be associated with hepatitis C virus infection without mixed cryoglobulinaemia.

 PMID:11171696

  15. Virus infection of Chlorella variabilis and enzymatic saccharification of algal biomass for bioethanol production.

    PubMed

    Cheng, Yu-Shen; Zheng, Yi; Labavitch, John M; VanderGheynst, Jean S

    2013-06-01

    Experiments were conducted to investigate the application of virus infection and amylolytic enzyme treatment on sugar release from Chlorella variabilis NC64A and bioethanol production from released sugars via Escherichia coli KO11 fermentation. Chlorella variabilis NC64A accumulated starch when it was cultured in a nitrogen-limited medium. The accumulated starch was not consumed during viral infection based on analysis of sugars released during infection. Both amylolytic enzyme addition and virus infection increased the hydrolysis of carbohydrates. Addition of amylolytic enzymes increased the release of glucose from algal biomass while virus addition increased the release of non-glucose neutral sugars. The combination of enzyme addition and virus infection also resulted in the highest ethanol production after fermentation. Acetic acid was generated as a co-product during fermentation in all sets of experiments. This study demonstrated that infection of microalgae with an algal virus resulted in disruption and hydrolysis of algal biomass to generate fermentable sugars.

  16. Molecular profiling of T-helper immune genes during dengue virus infection

    PubMed Central

    Chen, Jincheng; Ng, Mary Mah Lee; Chu, Justin Jang Hann

    2008-01-01

    In this study, we provide a comprehensive molecular profiling of the involvement of T- helper (Th) genes during dengue virus infection of different cell types. The Th gene profiles of three human cell types (monocytes, T-cells and hepatocytes) were analyzed simultaneously via array-based RT-PCR upon infection with dengue virus. Differential regulation of 41 Th genes was identified and of which 20 of those genes may contribute to immuno-pathogenesis of dengue virus infection by regulating inflammation, thrombocytopenia and vascular permeability. Among the strongly up-regulated genes were the RANTES, CC-CKR3, IRF4, CLEC2C, IL-6 and TLR6, which are potent inducer of inflammation and vascular permeability. Profiling genes obtained from this study may serve as potential biomarkers and the modulation of Th immune responses during dengue virus infection has important implications in disease outcome. PMID:19117515

  17. Eradication of bovine leukemia virus infection in commercial dairy herds using the agar gel immunodiffusion test.

    PubMed Central

    Shettigara, P T; Samagh, B S; Lobinowich, E M

    1986-01-01

    Demands for bovine leukemia virus test negative breeding cattle and for semen from bovine leukemia virus test negative bulls by several countries have encouraged the eradication of bovine leukemia virus infection from selected herds in Canada. This project was undertaken to evaluate the suitability of the agar gel immunodiffusion test, standardized to detect anti-bovine leukemia virus glycoprotein antibodies, for eradication of bovine leukemia virus from commercial dairy herds. Of nine participating herds, the prevalence rate of bovine leukemia virus infection was low (less than 10%) in three, medium (11-30%) in four and high (greater than 30%) in two. The herds were tested by the agar gel immunodiffusion test, reactors were removed and the herds were then retested at regular intervals. The results indicate that it is possible to eliminate bovine leukemia virus infection from the herds after two to three cycles of agar gel immunodiffusion tests and prompt removal of the reactors. PMID:3019498

  18. Protection against Influenza Virus Infection of Mice Fed Bifidobacterium breve YIT4064

    PubMed Central

    Yasui, Hisako; Kiyoshima, Junko; Hori, Tetuji; Shida, Kan

    1999-01-01

    Mice fed Bifidobacterium breve YIT4064 and immunized orally with influenza virus were more strongly protected against influenza virus infection of the lower respiratory tract than ones immunized with influenza virus only. The number of mice with enhanced anti-influenza virus immunoglobulin G (IgG) in serum upon oral administration of B. breve YIT4064 and oral immunization with influenza virus was significantly greater than that upon oral immunization with influenza virus only. These findings demonstrated that the oral administration of B. breve YIT4064 increased anti-influenza virus IgG antibodies in serum and protected against influenza virus infection. The oral administration of B. breve YIT4064 may enhance antigen-specific IgG against various pathogenic antigens taken orally and induce protection against various virus infections. PMID:10066652

  19. Immune inhibition of virus release from herpes simplex virus-infected cells by human sera.

    PubMed

    Shariff, D M; Hallworth, J; Desperbasques, M; Buchan, A; Skinner, G R

    1988-01-01

    Human sera contain antibody (IVR antibody) which will inhibit the release of herpes simplex virus type 1 from virus-infected cells. This antibody activity was removed by adsorption of sera with virus-infected cell extract. There was a positive correlation between IVR and neutralizing antibody activity, particularly when measured by augmented neutralization test; measurement of IVR antibody was equally as sensitive as measurement of neutralizing antibody by augmented neutralization test. IVR antibody levels provided indication of a history of recurrent herpes labialis, the pattern of antibody response following primary herpetic infection, and indication of response to Skinner herpes vaccine in human subjects. It is suggested that consideration should be given to measurement of IVR antibody in both clinical and epidemiological studies of herpes and other virus infections.

  20. Analysis of virus infected cell by Raman spectroscopy and transmission electron microscopy

    NASA Astrophysics Data System (ADS)

    Moor, Kamila; Ohtani, Kiyoshi; Myrzakozha, Diyas; Zhanserkenova, Orik; Andriana, Bibin B.; Sato, Hidetoshi

    2014-03-01

    Raman spectroscopy is a promising tool for detection of virus infection in live cells. In the present study, we demonstrate its feasibility to observe dynamic reaction of the live cell infected by virus. The Raman spectra of the adenovirus infected live cell (293 HEK) are analyzed by comparing with those of control cells. Principal component analysis (PCA) is employed also to analyze the spectra in detail. A band at 1650 cm-1 increases its intensity in the spectra measured at 24 hours after the virus infection. The infection of the virus is also examined by immune-staining and transmission electron microscope (TEM), and the virus infection is confirmed with these method also. It should be noted that the present technique does not require specifying the type of virus in advance.

  1. Expression of proinflammatory cytokines and its relationship with virus infection in the brain of macaques inoculated with macrophage-tropic simian immunodeficiency virus.

    PubMed

    Xing, Hui Qin; Moritoyo, Takashi; Mori, Kazuyasu; Sugimoto, Chie; Ono, Fumiko; Izumo, Shuji

    2009-02-01

    The pathogenesis of acquired immunodeficiency syndrome dementia complex (ADC) is still poorly understood. Many studies suggest that proinflammatory cytokines such as IL-1beta and TNF-alpha released by microglia/macrophages or astrocytes play a role in CNS injury. A microscopic finding of a microglial nodule with multinucleated giant cells (MNGCs) is a histopathologic hallmark of ADC and named HIV encephalitis. However, in vivo expression of these cytokines in this microenvironment of HIV encephalitis is not yet clarified. One of the main reasons is complexities of brain pathology in patients who have died from terminal AIDS. In this study, we infected two macaques with macrophage-tropic Simian immunodeficiency virus SIV239env/MERT and examined expression of TNF-alpha and IL-1beta in inflammatory lesions with MNGCs and its relation to virus-infected cells using immunohistochemistry. One macaque showed typical inflammatory lesions with MNGCs in the frontal white matter. Small microglial nodules were also detected in the basal ganglia and the spinal cord. SIVenv positive cells were detected mainly in inflammatory lesions, and seemed to be microglia/macrophages and MNGCs based on their morphology. Expression of IL-1beta and TNF-alpha were detected in the inflammatory lesions with MNGCs, and these positive cells were found to be negative for SIVenv by double-labeling immunohistochemistry or immunohistochemistry of serial sections. There were a few TNF-alpha positive cells and almost no IL-1beta positive cells in the area other than inflammatory lesions. Another macaque showed scattered CD3+ cells and CD68+ cells in the perivascular regions of the white matter. SIVenv and TNF-alpha was demonstrated in a few perivascular macrophages. These findings indicate that virus-infected microglia/macrophages do not always express IL-1beta and TNF-alpha, which suggests an indirect role of HIV-1-infected cells in cytokine-mediated pathogenesis of ADC. Our macaque model for human ADC

  2. Hunting in the Rainforest and Mayaro Virus Infection: An emerging Alphavirus in Ecuador

    PubMed Central

    Izurieta, Ricardo O; Macaluso, Maurizio; Watts, Douglas M; Tesh, Robert B; Guerra, Bolivar; Cruz, Ligia M; Galwankar, Sagar; Vermund, Sten H

    2011-01-01

    Objectives: The objectives of this report were to document the potential presence of Mayaro virus infection in Ecuador and to examine potential risk factors for Mayaro virus infection among the personnel of a military garrison in the Amazonian rainforest. Materials and Methods: The study population consisted of the personnel of a garrison located in the Ecuadorian Amazonian rainforest. The cross-sectional study employed interviews and seroepidemiological methods. Humoral immune response to Mayaro virus infection was assessed by evaluating IgM- and IgG-specific antibodies using ELISA. Results: Of 338 subjects studied, 174 were from the Coastal zone of Ecuador, 73 from Andean zone, and 91 were native to the Amazonian rainforest. Seroprevalence of Mayaro virus infection was more than 20 times higher among Amazonian natives (46%) than among subjects born in other areas (2%). Conclusions: Age and hunting in the rainforest were significant predictors of Mayaro virus infection overall and among Amazonian natives. The results provide the first demonstration of the potential presence of Mayaro virus infection in Ecuador and a systematic evaluation of risk factors for the transmission of this alphavirus. The large difference in prevalence rates between Amazonian natives and other groups and between older and younger natives suggest that Mayaro virus is endemic and enzootic in the rainforest, with sporadic outbreaks that determine differences in risk between birth cohorts of natives. Deep forest hunting may selectively expose native men, descendants of the Shuar and Huaronai ethnic groups, to the arthropod vectors of Mayaro virus in areas close to primate reservoirs. PMID:22223990

  3. Cytokine production by blue tongue virus-infected fetal sheep cells.

    PubMed Central

    Enright, F M; Osburn, B I

    1979-01-01

    The migration inhibition of guinea pig peritoneal macrophages by a factor(s) from media obtained from blue tongue virus-infected monolayer cultures was studied. Medium from blue tongue virus-infected sheep fetal cell cultures inhibited migration of guinea pig macrophages from agarose droplets. Medium from control cultures and stock virus did not inhibit macrophage migration. Medium containing migration inhibiting factor(s) in vitro induced an inflammatory reaction in the skin of a newborn sheep. The inflammatory reaction was observed 20 h after intradermal inoculation. The skin reaction consisted of infiltrates of mononuclear leukocytes in the superficial dermis. Control medium and stock virus caused no skin reaction. Images PMID:225275

  4. The Drug Targets and Antiviral Molecules for Treatment of Ebola Virus Infection.

    PubMed

    Wu, Wenjiao; Liu, Shuwen

    2017-01-01

    Ebola virus (EBOV) is a highly pathogenic virus causing severe hemorrhagic fever with a high case fatality rate of 50% - 90% in humans. Without an approved vaccine or treatments, Ebola outbreak management has been limited to palliative care and barrier methods to prevent transmission. These approaches, however, have yet to end the 2014 outbreak of Ebola after its prolonged presence in West Africa. As with the increase of outbreaks, a significant effort has been made to develop promising countermeasures for the prevention and treatment of Ebola virus infection. In this review, development of therapeutics and potential inhibitors for Ebola virus infection will be discussed.

  5. Clinical and biological differences between recurrent herpes simplex virus and varicella-zoster virus infections

    SciTech Connect

    Straus, S.E. )

    1989-12-01

    The major features that distinguish recurrent herpes simplex virus infections from zoster are illustrated in this article by two case histories. The clinical and epidemiologic features that characterize recurrent herpes simplex virus and varicella-zoster virus infections are reviewed. It is noted that herpesvirus infections are more common and severe in patients with cellular immune deficiency. Each virus evokes both humoral and cellular immune response in the course of primary infection. DNA hybridization studies with RNA probes labelled with sulfur-35 indicate that herpes simplex viruses persist within neurons, and that varicella-zoster virus is found in the satellite cells that encircle the neurons.

  6. Pandemic (H1N1) 2009 Influenza Virus Infection in A Survivor Who Has Recovered from Severe H7N9 Virus Infection, China

    PubMed Central

    Chen, Shan-Hui; Wu, Meng-Na; Qian, Yan-Hua; Ma, Guang-Yuan; Wang, Guo-Lin; Yang, Yang; Zhao, Teng; Lu, Bing; Ma, Mai-Juan; Cao, Wu-Chun

    2016-01-01

    We firstly report a patient who presented with severe complications after infection with influenza A(H1N1) pdm2009, more than 1 year after recovery from severe H7N9 virus infections. The population of patients who recovered from severe H7N9 infections might be at a higher risk to suffer severe complications after seasonal influenza infections, and they should be included in the high-risk populations recommended to receive seasonal influenza vaccination. PMID:27757100

  7. Molecular signatures associated with Mx-1 mediated resistance to highlyl pathogenic influenza virus infections: mechanisms of survival

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Understanding the role of host factors during lethal influenza virus infection is critical to deciphering the events that will determine the fate of the host. One such factor is encoded by the Mx1 gene, which confers resistance to influenza virus infection. Here, we compared pathology and global g...

  8. Reading Recovery Following Herpes Encephalitis.

    ERIC Educational Resources Information Center

    Rogers, C. D.; Peters, Phyllis

    1979-01-01

    The article presents the medical, psychological, and reading diagnoses of a 24-year-old man with herpes encephalitis, an acute neurological disease. Test results are reported and the client's response to learning disability remedial techniques are reviewed. (SBH)

  9. Neuropathology of H5N1 virus infection in ferrets.

    PubMed

    Peng, Bi-Hung; Yun, Nadezhda; Chumakova, Olga; Zacks, Michele; Campbell, Gerald; Smith, Jeanon; Smith, Jennifer; Linde, Seth; Linde, Jenna; Paessler, Slobodan

    2012-05-04

    Highly pathogenic H5N1 virus remains a potential threat to humans. Over 289 fatalities have been reported in WHO confirmed human cases since 2003, and lack of effective vaccines and early treatments contribute to increasing numbers of cases and fatalities. H5N1 encephalitis is a recognized cause of death in Vietnamese cases, and brain pathology is described in other human cases and naturally infected animals. However, neither pathogenesis of H5N1 viral infection in human brain nor post-infection effects in survivors have been fully investigated. We report the brain pathology in a ferret model for active infection and 18-day survival stages. This model closely resembles the infection pattern and progression in human cases of influenza A, and our report is the first description of brain pathology for longer term (18-day) survival in ferrets. We analyzed viral replication, type and severity of meningoencephalitis, infected cell types, and cellular responses to infection. We found viral replication to very high titers in ferret brain, closely correlating with severity of meningoencephalitis. Viral antigens were detected predominantly in neurons, correlating with inflammatory lesions, and less frequently in astrocytes and ependymal cells during active infection. Mononuclear cell infiltrates were observed in early stages predominantly in cerebral cortex, brainstem, and leptomeninges, and less commonly in cerebellum and other areas. Astrogliosis was mild at day 4 post-infection, but robust by day 18. Early and continuous treatment with an antiviral agent (peramivir) inhibited virus production to non-detectable levels, reduced severity of brain injury, and promoted higher survival rates.

  10. A new reportable disease is born: Taiwan Centers for Disease Control's response to emerging Zika virus infection.

    PubMed

    Huang, Angela Song-En; Shu, Pei-Yun; Yang, Chin-Hui

    2016-04-01

    Zika virus infection, usually a mild disease transmitted through the bite of Aedes mosquitos, has been reported to be possibly associated with microcephaly and neurologic complications. Taiwan's first imported case of Zika virus infection was found through fever screening at airport entry in January 2016. No virus was isolated from patient's blood taken during acute illness; however, PCR products showed that the virus was of Asian lineage closely related to virus from Cambodia. To prevent Zika virus from spreading in Taiwan, the Taiwan Centers for Disease Control has strengthened efforts in quarantine and surveillance, increased Zika virus infection diagnostic capacity, implemented healthcare system preparedness plans, and enhanced vector control program through community mobilization and education. Besides the first imported case, no additional cases of Zika virus infection have been identified. Furthermore, no significant increase in the number of microcephaly or Guillain- Barré Syndrome has been observed in Taiwan. To date, there have been no autochthonous transmissions of Zika virus infection.

  11. Epitope Identification and Application for Diagnosis of Duck Tembusu Virus Infections in Ducks.

    PubMed

    Li, Chenxi; Liu, Junyan; Shaozhou, Wulin; Bai, Xiaofei; Zhang, Qingshan; Hua, Ronghong; Liu, Jyung-Hurng; Liu, Ming; Zhang, Yun

    2016-11-10

    Duck Tembusu virus (DTMUV) causes substantial egg drop disease. DTMUV was first identified in China and rapidly spread to Malaysia and Thailand. The antigenicity of the DTMUV E protein has not yet been characterized. Here, we investigated antigenic sites on the E protein using the non-neutralizing monoclonal antibodies (mAbs) 1F3 and 1A5. Two minimal epitopes were mapped to (221)LD/NLPW(225) and (87)YAEYI(91) by using phage display and mutagenesis. DTMUV-positive duck sera reacted with the epitopes, thus indicating the importance of the minimal amino acids of the epitopes for antibody-epitope binding. The performance of the dot blotting assay with the corresponding positive sera indicated that YAEYI was DTMUV type-specific, whereas (221)LD/NLPW(225) was a cross-reactive epitope for West Nile virus (WNV), dengue virus (DENV), and Japanese encephalitis virus (JEV) and corresponded to conserved and variable amino acid sequences among these strains. The structure model of the E protein revealed that YAEYI and LD/NLPW were located on domain (D) II, which confirmed that DII might contain a type-specific non-neutralizing epitope. The YAEYI epitope-based antigen demonstrated its diagnostic potential by reacting with high specificity to serum samples obtained from DTMUV-infected ducks. Based on these observations, a YAEYI-based serological test could be used for DTMUV surveillance and could differentiate DTMUV infections from JEV or WNV infections. These findings provide new insights into the organization of epitopes on flavivirus E proteins that might be valuable for the development of epitope-based serological diagnostic tests for DTMUV.

  12. Epitope Identification and Application for Diagnosis of Duck Tembusu Virus Infections in Ducks

    PubMed Central

    Li, Chenxi; Liu, Junyan; Shaozhou, Wulin; Bai, Xiaofei; Zhang, Qingshan; Hua, Ronghong; Liu, Jyung-Hurng; Liu, Ming; Zhang, Yun

    2016-01-01

    Duck Tembusu virus (DTMUV) causes substantial egg drop disease. DTMUV was first identified in China and rapidly spread to Malaysia and Thailand. The antigenicity of the DTMUV E protein has not yet been characterized. Here, we investigated antigenic sites on the E protein using the non-neutralizing monoclonal antibodies (mAbs) 1F3 and 1A5. Two minimal epitopes were mapped to 221LD/NLPW225 and 87YAEYI91 by using phage display and mutagenesis. DTMUV-positive duck sera reacted with the epitopes, thus indicating the importance of the minimal amino acids of the epitopes for antibody-epitope binding. The performance of the dot blotting assay with the corresponding positive sera indicated that YAEYI was DTMUV type-specific, whereas 221LD/NLPW225 was a cross-reactive epitope for West Nile virus (WNV), dengue virus (DENV), and Japanese encephalitis virus (JEV) and corresponded to conserved and variable amino acid sequences among these strains. The structure model of the E protein revealed that YAEYI and LD/NLPW were located on domain (D) II, which confirmed that DII might contain a type-specific non-neutralizing epitope. The YAEYI epitope-based antigen demonstrated its diagnostic potential by reacting with high specificity to serum samples obtained from DTMUV-infected ducks. Based on these observations, a YAEYI-based serological test could be used for DTMUV surveillance and could differentiate DTMUV infections from JEV or WNV infections. These findings provide new insights into the organization of epitopes on flavivirus E proteins that might be valuable for the development of epitope-based serological diagnostic tests for DTMUV. PMID:27834908

  13. Genetic variation of St. Louis encephalitis virus.

    PubMed

    May, Fiona J; Li, Li; Zhang, Shuliu; Guzman, Hilda; Beasley, David W C; Tesh, Robert B; Higgs, Stephen; Raj, Pushker; Bueno, Rudy; Randle, Yvonne; Chandler, Laura; Barrett, Alan D T

    2008-08-01

    St. Louis encephalitis virus (SLEV) has been regularly isolated throughout the Americas since 1933. Previous phylogenetic studies involving 62 isolates have defined seven major lineages (I-VII), further divided into 14 clades. In this study, 28 strains isolated in Texas in 1991 and 2001-2003, and three older, previously unsequenced strains from Jamaica and California were sequenced over the envelope protein gene. The inclusion of these new sequences, and others published since 2001, has allowed better delineation of the previously published SLEV lineages, in particular the clades of lineage II. Phylogenetic analysis of 106 isolates identified 13 clades. All 1991 and 2001-2003 isolates from Nueces, Jefferson and Harris Counties (Texas Gulf Coast) group in clade IIB with other isolates from these counties isolated during the 1980s and 1990s. This lack of evidence for introduction of novel strains into the Texas Gulf Coast over a long period of time is consistent with overwintering of SLEV in this region. Two El Paso isolates, both from 2002, group in clade VA with recent Californian isolates from 1998-2001 and some South American strains with a broad temporal range. Overall, these data are consistent with multiple introductions of SLEV from South America into North America, and provide support for the hypothesis that in most situations, SLEV circulates within a locality, with occasional incursions from other areas. Finally, SLEV has much lower nucleotide (10.1 %) and amino acid variation (2.8 %) than other members of the Japanese encephalitis virus complex (maximum variation 24.6 % nucleotide and 11.8 % amino acid).

  14. Non-coding RNAs and heme oxygenase-1 in vaccinia virus infection

    SciTech Connect

    Meseda, Clement A.; Srinivasan, Kumar; Wise, Jasen; Catalano, Jennifer; Yamada, Kenneth M.; Dhawan, Subhash

    2014-11-07

    Highlights: • Heme oxygenase-1 (HO-1) induction inhibited vaccinia virus infection of macrophages. • Reduced infectivity inversely correlated with increased expression of non-coding RNAs. • The regulation of HO-1 and ncRNAs suggests a novel host defense response against vaccinia virus infection. - Abstract: Small nuclear RNAs (snRNAs) are <200 nucleotide non-coding uridylate-rich RNAs. Although the functions of many snRNAs remain undetermined, a population of snRNAs is produced during the early phase of infection of cells by vaccinia virus. In the present study, we demonstrate a direct correlation between expression of the cytoprotective enzyme heme oxygenase-1 (HO-1), suppression of selective snRNA expression, and inhibition of vaccinia virus infection of macrophages. Hemin induced HO-1 expression, completely reversed virus-induced host snRNA expression, and suppressed vaccinia virus infection. This involvement of specific virus-induced snRNAs and associated gene clusters suggests a novel HO-1-dependent host-defense pathway in poxvirus infection.

  15. Multiple virus infections occur in individual polygyne and monogyne Solenopsis invicta ants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Concurrent infections of Solenopsis invicta colonies with Solenopsis invicta virus 1 to 3 (SINV-1, SINV-2 and SINV-3) has been reported. However, whether individual ants were capable of supporting multiple virus infections simultaneously was not known, nor whether the social form of the colony (pol...

  16. Milk and fat production in dairy cattle influenced by advanced subclinical bovine leukemia virus infection.

    PubMed Central

    Wu, M C; Shanks, R D; Lewin, H A

    1989-01-01

    Genetic potentials (pedigree-estimated breeding value) for milk and for fat were compared in cows grouped according to subclinical stage of bovine leukemia virus infection. Genetic potential for milk production was significantly greater in seropositive cows with persistent lymphocytosis (622 +/- 72 kg) and in seropositive hematologically normal cows (554 +/- 34 34 kg) than in seronegative herdmates (418 +/- 53 kg). When 305-day twice-daily-milking mature equivalent milk production records for the current lactation were adjusted for genetic potential, bovine leukemia virus-infected cows that were hematologically normal had significantly greater milk production than did seronegative herdmates, suggesting that early bovine leukemia virus infection was positively associated with milk yield. Genetic potential for fat production was significantly greater for cows with persistent lymphocytosis (21 +/- 2 kg) than for other seropositive (16 +/- 1 kg) and seronegative herdmates (13 +/- 2 kg); however, 305-day twice-daily-milking mature equivalent fat production for the current lactation was not significantly different between the groups. Thus, cows with persistent lymphocytosis did not produce fat according to their genetic potential. As an apparent consequence of tendencies for greater milk yield and less fat production, milk fat percentage was significantly reduced in cows with persistent lymphocytosis (3.33 +/- 0.09%) and other seropositive cows (3.48 +/- 0.05%) relative to seronegative herdmates (3.67 +/- 0.07%). These results suggest a need to reevaluate the economic impact of bovine leukemia virus infection on the dairy industry. PMID:2536940

  17. Zika Virus Infection and Prolonged Viremia in Whole-Blood Specimens.

    PubMed

    Mansuy, Jean Michel; Mengelle, Catherine; Pasquier, Christophe; Chapuy-Regaud, Sabine; Delobel, Pierre; Martin-Blondel, Guillaume; Izopet, Jacques

    2017-05-15

    We tested whole-blood and plasma samples from immunocompetent patients who had had benign Zika virus infections and found that Zika virus RNA persisted in whole blood substantially longer than in plasma. This finding may have implications for diagnosis of acute symptomatic and asymptomatic infections and for testing of blood donations.

  18. Modification of non-vector aphid feeding behavior on virus-infected host plant.

    PubMed

    Hu, Zuqing; Zhao, Huiyan; Thieme, Thomas

    2013-01-01

    Virus-infected host plants can have positive, neutral or negative effects on vector aphids. Even though the proportion of non-vector aphids associated with a plant far exceeds that of vector species, little is known about the effect of virus-infected plants on non-vector aphids. In the present study, the English grain aphid Sitobion avenae (Fabricius) (Hemiptera: Aphididae), a non-vector of Wheat dwarf virus (WDV) and Cereal yellow dwarf virus-RPV (CYDV-RPV), was monitored on, virus-infected, virus-free and leafhopper/aphid-infested, and virus- and insect-free (control) barley, Hordeum vulgare L. (Poales: Poaceae), plants. Electrical penetration graph recordings were performed. Compared with the control plants, S. avenae on infected plants exhibited reduced non-probing and pathway phase, and increased phloem sap ingestion phase, and more aphids reached sustained phloem ingestion. However, the electrical penetration graph parameters described above showed no significant differences in aphid feeding behavior on virus-free and vector pre-infested plants and the control barley plants during S. avenae feeding. The results suggest that WDV/CYDV-RPV-infected host plants positively affected the feeding behavior of the non-vector aphid S. avenae. Based on these results, the reasons and trends among the virus-infected host plants' effects on the feeding behavior of non-vector aphids are discussed.

  19. Effect of phenylhydrazine pretreatment on splenectomized Rauscher leukemia virus-infected mice.

    PubMed

    Bergson, A; Lobue, J; Gordon, A S; Fredickson, T N

    1978-01-01

    The protective effect of phenylhydrazine pretreatment seen in Rauscher leukemia virus-infected intact mice is not observed when splenectomized mice are used. Such mice succumb to infection even earlier than viral potency controls. Since phenylhydrazine is known to increase both splenic erythropoiesis and hematopoietic stem cell numbers, the results suggest that these two events may be involved in phenylhydrazine prophylaxis.

  20. Virus infection mediates the effects of elevated CO2 on plants and vectors

    NASA Astrophysics Data System (ADS)

    Trębicki, Piotr; Vandegeer, Rebecca K.; Bosque-Pérez, Nilsa A.; Powell, Kevin S.; Dader, Beatriz; Freeman, Angela J.; Yen, Alan L.; Fitzgerald, Glenn J.; Luck, Jo E.

    2016-03-01

    Atmospheric carbon dioxide (CO2) concentration has increased significantly and is projected to double by 2100. To increase current food production levels, understanding how pests and diseases respond to future climate driven by increasing CO2 is imperative. We investigated the effects of elevated CO2 (eCO2) on the interactions among wheat (cv. Yitpi), Barley yellow dwarf virus and an important pest and virus vector, the bird cherry-oat aphid (Rhopalosiphum padi), by examining aphid life history, feeding behavior and plant physiology and biochemistry. Our results showed for the first time that virus infection can mediate effects of eCO2 on plants and pathogen vectors. Changes in plant N concentration influenced aphid life history and behavior, and N concentration was affected by virus infection under eCO2. We observed a reduction in aphid population size and increased feeding damage on noninfected plants under eCO2 but no changes to population and feeding on virus-infected plants irrespective of CO2 treatment. We expect potentially lower future aphid populations on noninfected plants but no change or increased aphid populations on virus-infected plants therefore subsequent virus spread. Our findings underscore the complexity of interactions between plants, insects and viruses under future climate with implications for plant disease epidemiology and crop production.

  1. Blood Feeding Behavior of Vesicular Stomatitis Virus Infected Culicoides Sonorensis (Diptera: Ceratopogonidae)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To determine whether vesicular stomatitis virus (VSV) infection of Culicoides sonorensis affects subsequent blood feeding behavior, midges injected with either virus-infected or virus-free cell lysates were allowed to blood feed for short (10 min) or long (60 min) periods of time on days 2, 3, and 4...

  2. Therapeutic effects of garenoxacin in murine experimental secondary pneumonia by Streptococcus pneumoniae after influenza virus infection.

    PubMed

    Fukuda, Yoshiko; Furuya, Yuri; Nozaki, Yusuke; Takahata, Masahiro; Nomura, Nobuhiko; Mitsuyama, Junichi

    2014-02-01

    In a pneumococcal pneumonia murine model following influenza virus infection, garenoxacin was more effective than other fluoroquinolones and demonstrated high levels of bacterial eradication in the lung, low mortality, and potent histopathological improvements. Garenoxacin could potentially be used for the treatment of secondary pneumococcal pneumonia following influenza.

  3. [Liberation into the wild of wild felines--danger of the release of virus infections].

    PubMed

    Lutz, H; Hofmann-Lehmann, R; Fehr, D; Leutenegger, C; Hartmann, M; Ossent, P; Grob, M; Elgizoli, M; Weilenmann, P

    1996-01-01

    There are several felidae amongst the numerous endangered species. Means of aiding survival are the reintroduction to the wild of animals bred under the auspices of man and their relocation from densely populated to thinly populated areas. It is unlikely that the dangers of such reintroduction or relocation projects have been examined sufficiently in respect to the risks of virus infections confronting individuals kept in zoos or similar situations. This report presents three examples to illustrate that accidental virus infections may be expected to occur when relocating and reintroducing wild cats. The first example is the reintroduction of captive snow leopards. Zoo bred snow leopards may be infected with FIV, a virus infection that is highly unlikely to occur in the original himalayan highlands of Tibet and China. A second example is of several cases of FIP that occurred in European wild cats bred in groups in captivity. The third example mentioned is the relocation of lions from East Africa where all the commonly known feline viruses are wide-spread to the Etosha National Park. In the latter, virus infections such as FIV, FCV and FPV do not occur. The indiscriminate relocation and reintroduction of the wild cats mentioned here harbours a potential of undesirable consequences.

  4. Virus infection mediates the effects of elevated CO2 on plants and vectors

    PubMed Central

    Trębicki, Piotr; Vandegeer, Rebecca K.; Bosque-Pérez, Nilsa A.; Powell, Kevin S.; Dader, Beatriz; Freeman, Angela J.; Yen, Alan L.; Fitzgerald, Glenn J.; Luck, Jo E.

    2016-01-01

    Atmospheric carbon dioxide (CO2) concentration has increased significantly and is projected to double by 2100. To increase current food production levels, understanding how pests and diseases respond to future climate driven by increasing CO2 is imperative. We investigated the effects of elevated CO2 (eCO2) on the interactions among wheat (cv. Yitpi), Barley yellow dwarf virus and an important pest and virus vector, the bird cherry-oat aphid (Rhopalosiphum padi), by examining aphid life history, feeding behavior and plant physiology and biochemistry. Our results showed for the first time that virus infection can mediate effects of eCO2 on plants and pathogen vectors. Changes in plant N concentration influenced aphid life history and behavior, and N concentration was affected by virus infection under eCO2. We observed a reduction in aphid population size and increased feeding damage on noninfected plants under eCO2 but no changes to population and feeding on virus-infected plants irrespective of CO2 treatment. We expect potentially lower future aphid populations on noninfected plants but no change or increased aphid populations on virus-infected plants therefore subsequent virus spread. Our findings underscore the complexity of interactions between plants, insects and viruses under future climate with implications for plant disease epidemiology and crop production. PMID:26941044

  5. Infants with Congenital Zika Virus Infection: A New Challenge for Early Intervention Professionals

    ERIC Educational Resources Information Center

    Porter, Sallie; Mimm, Nancy

    2017-01-01

    Zika virus infection-associated microcephaly has generated public health and media concern. Unsettling images emerging from Brazil of infants with abnormally small heads have raised concern among women of childbearing age, international travelers, government officials, and health care professionals. The World Health Organization declared the most…

  6. l-carbocisteine inhibits respiratory syncytial virus infection in human tracheal epithelial cells.

    PubMed

    Asada, Masanori; Yoshida, Motoki; Hatachi, Yukimasa; Sasaki, Takahiko; Yasuda, Hiroyasu; Deng, Xue; Nishimura, Hidekazu; Kubo, Hiroshi; Nagatomi, Ryoichi; Yamaya, Mutsuo

    2012-01-15

    To examine the effects of l-carbocisteine on airway infection with respiratory syncytial (RS) virus, human tracheal epithelial cells were pretreated with l-carbocisteine and infected with RS virus. Viral titer, virus RNA, and pro-inflammatory cytokine secretion, including interleukin (IL)-1 and IL-6, increased with time after infection. l-carbocisteine reduced the viral titer in the supernatant fluids, the amount of RS virus RNA, RS virus infection susceptibility, and the concentration of pro-inflammatory cytokines induced by virus infection. l-carbocisteine reduced the expression of intercellular adhesion molecule (ICAM)-1, an RS virus receptor, on the cells. However, l-carbocisteine had no effects on the expression of heparan sulfate, a glycosaminoglycan that binds to the RS virus attachment protein, or on the amount of intracellular activated-RhoA, isoform A of the Ras-homologous family, that binds to the RS virus fusion protein. These findings suggest that l-carbocisteine may inhibit RS virus infection by reducing the expression of ICAM-1. It may also modulate airway inflammation during RS virus infection.

  7. Clinical West Nile virus infection in 2 horses in western Canada.

    PubMed

    Abutarbush, Sameeh M; O'Connor, Brendan P; Clark, Chris; Sampieri, Francesca; Naylor, Jonathan M

    2004-04-01

    Two horses had a history of ataxia and weakness or recumbency. One recovered and was diagnosed with West Nile virus (WNV) infection by serologic testing. The other was euthanized; it had meningoencephalomyelitis, WNV was detected by polymerase chain reaction. West Nile virus infection is an emerging disease. Year 2002 is the first year in which cases have been seen in Saskatchewan.

  8. Clinical West Nile virus infection in 2 horses in western Canada

    PubMed Central

    2004-01-01

    Abstract Two horses had a history of ataxia and weakness or recumbency. One recovered and was diagnosed with West Nile virus (WNV) infection by serologic testing. The other was euthanized; it had meningoencephalomyelitis, WNV was detected by polymerase chain reaction. West Nile virus infection is an emerging disease. Year 2002 is the first year in which cases have been seen in Saskatchewan. PMID:15144104

  9. Severe Neurologic Disorders in 2 Fetuses with Zika Virus Infection, Colombia.

    PubMed

    Acosta-Reyes, Jorge; Navarro, Edgar; Herrera, Maria José; Goenaga, Eloina; Ospina, Martha L; Parra, Edgar; Mercado, Marcela; Chaparro, Pablo; Beltran, Mauricio; Gunturiz, Maria Luz; Pardo, Lissethe; Valencia, Catalina; Huertas, Sandra; Rodríguez, Jorge; Ruiz, Germán; Valencia, Diana; Haddad, Lisa B; Tinker, Sarah C; Moore, Cynthia A; Baquero, Hernando

    2017-06-15

    We report the results of pathologic examinations of 2 fetuses from women in Colombia with Zika virus infection during pregnancy that revealed severe central nervous system defects and potential associated abnormalities of the eye, spleen, and placenta. Amniotic fluid and tissues from multiple fetal organs tested positive for Zika virus.

  10. West Nile virus infection among humans, Texas, USA, 2002-2011.

    PubMed

    Nolan, Melissa S; Schuermann, Jim; Murray, Kristy O

    2013-01-01

    We conducted an epidemiologic analysis to document West Nile virus infections among humans in Texas, USA, during 2002-2011. West Nile virus has become endemic to Texas; the number of reported cases increased every 3 years. Risk for infection was greatest in rural northwestern Texas, where Culex tarsalis mosquitoes are the predominant mosquito species.

  11. Milk and fat production in dairy cattle influenced by advanced subclinical bovine leukemia virus infection.

    PubMed

    Wu, M C; Shanks, R D; Lewin, H A

    1989-02-01

    Genetic potentials (pedigree-estimated breeding value) for milk and for fat were compared in cows grouped according to subclinical stage of bovine leukemia virus infection. Genetic potential for milk production was significantly greater in seropositive cows with persistent lymphocytosis (622 +/- 72 kg) and in seropositive hematologically normal cows (554 +/- 34 34 kg) than in seronegative herdmates (418 +/- 53 kg). When 305-day twice-daily-milking mature equivalent milk production records for the current lactation were adjusted for genetic potential, bovine leukemia virus-infected cows that were hematologically normal had significantly greater milk production than did seronegative herdmates, suggesting that early bovine leukemia virus infection was positively associated with milk yield. Genetic potential for fat production was significantly greater for cows with persistent lymphocytosis (21 +/- 2 kg) than for other seropositive (16 +/- 1 kg) and seronegative herdmates (13 +/- 2 kg); however, 305-day twice-daily-milking mature equivalent fat production for the current lactation was not significantly different between the groups. Thus, cows with persistent lymphocytosis did not produce fat according to their genetic potential. As an apparent consequence of tendencies for greater milk yield and less fat production, milk fat percentage was significantly reduced in cows with persistent lymphocytosis (3.33 +/- 0.09%) and other seropositive cows (3.48 +/- 0.05%) relative to seronegative herdmates (3.67 +/- 0.07%). These results suggest a need to reevaluate the economic impact of bovine leukemia virus infection on the dairy industry.

  12. Giant cell arteritis associated with chronic active Epstein-Barr virus infection.

    PubMed

    Giardina, A; Rizzo, A; Ferrante, A; Capra, G; Triolo, G; Ciccia, F

    2013-03-28

    Giant cell arteritis is an inflammatory vasculopathy that preferentially affects medium-sized and large arteries. A viral cause has been suspected but not confirmed in polymyalgia rheumatica and giant-cell arteritis. We report the case of a 81-year-old female who suffered from chronic active Epstein-Barr virus infection and developed giant cell temporal arteritis.

  13. [Identification of plant viruses infecting transgenic potatoes resistant to the Colorado beetle].

    PubMed

    Mel'nychuk, M D; Spyrydonov, V G

    2001-01-01

    Virus tolerance of the three varieties of Bt-potato New Leaf--Atlantic, Russet Burbank and Superior from "Monsanto company" has been studied. Using serology, biochemistry methods and biotest the mixed virus infecting of experimental plants has been shown. Virus transmission by infected potato root crops under reproduction and accelerated degradation processes during storage have been registered.

  14. Modeling within-host dynamics of influenza virus infection including immune responses.

    PubMed

    Pawelek, Kasia A; Huynh, Giao T; Quinlivan, Michelle; Cullinane, Ann; Rong, Libin; Perelson, Alan S

    2012-01-01

    Influenza virus infection remains a public health problem worldwide. The mechanisms underlying viral control during an uncomplicated influenza virus infection are not fully understood. Here, we developed a mathematical model including both innate and adaptive immune responses to study the within-host dynamics of equine influenza virus infection in horses. By comparing modeling predictions with both interferon and viral kinetic data, we examined the relative roles of target cell availability, and innate and adaptive immune responses in controlling the virus. Our results show that the rapid and substantial viral decline (about 2 to 4 logs within 1 day) after the peak can be explained by the killing of infected cells mediated by interferon activated cells, such as natural killer cells, during the innate immune response. After the viral load declines to a lower level, the loss of interferon-induced antiviral effect and an increased availability of target cells due to loss of the antiviral state can explain the observed short phase of viral plateau in which the viral level remains unchanged or even experiences a minor second peak in some animals. An adaptive immune response is needed in our model to explain the eventual viral clearance. This study provides a quantitative understanding of the biological factors that can explain the viral and interferon kinetics during a typical influenza virus infection.

  15. Transient CD4/CD8 ratio inversion and aberrant immune activation during dengue virus infection.

    PubMed

    Liu, Ching-Chuan; Huang, Kao-Jean; Lin, Yee-Shin; Yeh, Trai-Ming; Liu, Hsiao-Sheng; Lei, Huan-Yao

    2002-10-01

    The immune status after dengue virus infection was studied in dengue patients from an outbreak of serotype 3 dengue virus infection in the southern part of Taiwan during November and December 1998. Consecutive blood samples from 29 dengue patients, of whom 21 had dengue fever and 8 had dengue hemorrhagic fever/dengue shock syndrome, were collected, and the immunophenotypes of the peripheral blood mononuclear cells were determined by flow cytometry. The early activation marker CD69 appeared on lymphocytes and monocytes at day 4 after the onset of fever, and declined afterward. However, a transient reverse in the CD4/CD8 ratio occurred at days 6-10 after the onset of fever. The CD4/CD8 ratio inversion was manifested in 10 of 29 dengue patients and was encountered more frequently in dengue hemorrhagic fever/dengue shock syndrome than in dengue fever patients. Analysis of the clinical blood cell count of these 10 cases showed that increase of immature neutrophils developed at fever days 5-6, CD4(dim) or CD8(dim) monocytosis at days 6-7, and atypical lymphocytosis at days 8-10 after the onset of fever. Serum IL-6 was found at either day 7 or day 9-11. The PHA-stimulated T-cell response was depressed as well. These changes in immune parameters indicate aberrant immune activation during dengue virus infection and might be involved in the pathogenesis of dengue virus infection.

  16. Hyperferritinaemia in Dengue Virus Infected Patients Is Associated with Immune Activation and Coagulation Disturbances

    PubMed Central

    Pannuti, Cláudio S.; Brouns, Rosalba M.; van den Berg, Riemsdijk W. A.; van den Ham, Henk-Jan; Martina, Byron E. E.; Osterhaus, Albert D. M. E.; Netea, Mihai G.; Meijers, Joost C. M.; van Gorp, Eric C. M.; Kallas, Esper G.

    2014-01-01

    Background During a dengue outbreak on the Caribbean island Aruba, highly elevated levels of ferritin were detected in dengue virus infected patients. Ferritin is an acute-phase reactant and hyperferritinaemia is a hallmark of diseases caused by extensive immune activation, such as haemophagocytic lymphohistiocytosis. The aim of this study was to investigate whether hyperferritinaemia in dengue patients was associated with clinical markers of extensive immune activation and coagulation disturbances. Methodology/Principal Findings Levels of ferritin, standard laboratory markers, sIL-2R, IL-18 and coagulation and fibrinolytic markers were determined in samples from patients with uncomplicated dengue in Aruba. Levels of ferritin were significantly increased in dengue patients compared to patients with other febrile illnesses. Moreover, levels of ferritin associated significantly with the occurrence of viraemia. Hyperferritinaemia was also significantly associated with thrombocytopenia, elevated liver enzymes and coagulation disturbances. The results were validated in a cohort of dengue virus infected patients in Brazil. In this cohort levels of ferritin and cytokine profiles were determined. Increased levels of ferritin in dengue virus infected patients in Brazil were associated with disease severity and a pro-inflammatory cytokine profile. Conclusions/Significance Altogether, we provide evidence that ferritin can be used as a clinical marker to discriminate between dengue and other febrile illnesses. The occurrence of hyperferritinaemia in dengue virus infected patients is indicative for highly active disease resulting in immune activation and coagulation disturbances. Therefore, we recommend that patients with hyperferritinaemia are monitored carefully. PMID:25299654

  17. Novel agents and strategies to treat herpes simplex virus infections.

    PubMed

    Kleymann, Gerald

    2003-02-01

    The quiet pandemic of herpes simplex virus (HSV) infection has plagued humanity since ancient times, causing mucocutaneous infection, such as herpes labialis and herpes genitalis. Disease symptoms often interfere with everyday activities and occasionally HSV infections are the cause of life-threatening or sight-impairing disease, especially in neonates and the immunocompromised patient population. After primary or initial infection the virus persists for life in a latent form in neurons of the host, periodically reactivating and often resulting in significant psychosocial distress for the patient. Currently, no cure is available. In the mid-1950s the first antiviral, idoxuridine, was developed for topical treatment of herpes disease and, in 1978, vidarabine was licensed for systemic use to treat HSV encephalitis. Acyclovir (Zovirax), a potent, specific and tolerable nucleosidic inhibitor of the herpes DNA polymerase, was a milestone in the development of antiviral drugs in the late 1970s. In the mid-1990s, when acyclovir became a generic drug, valacyclovir (Valtrex) and famciclovir (Famvir), prodrugs of the gold standard and penciclovir (Denavir), Vectavir), a close analogue, were launched. Though numerous approaches and strategies were tested and considerable effort was expended in the search of the next generation of an antiherpetic therapy, it proved difficult to outperform acyclovir. Notable in this regard was the award of a Nobel Prize in 1988 for the elucidation of mechanistic principles which resulted in the development of new drugs such as acyclovir. Vaccines, interleukins, interferons, therapeutic proteins, antibodies, immunomodulators and small-molecule drugs with specific or nonspecific modes of action lacked either efficacy or the required safety profile to replace the nucleosidic drugs acyclovir, valacyclovir, penciclovir and famciclovir as the first choice of treatment. Recently though, new inhibitors of the HSV helicase-primase with potent in vitro

  18. Tick-borne encephalitis virus foci in Slovakia.

    PubMed

    Labuda, Milan; Elecková, Elena; Licková, Martina; Sabó, Alexander

    2002-06-01

    Tick-borne encephalitis (TBE) virus as a typical arbovirus relies on two types of hosts for its survival: ticks act both as virus vectors and reservoir hosts, and vertebrates amplify the virus infection by acting as a source of infection for feeding ticks. Longitudinal monitoring of TBE virus in ticks and vertebrate hosts including humans over a period of 40 years resulted in the identification of the areas of Slovakia where TBE virus is endemic. These are concentrated to the western, southern, and eastern parts of the country. Even with recently identified foci there is no evidence that the size and location of the natural TBE foci have changed significantly during the last decades. Numbers of diagnosed hospitalised cases of TBE in Slovakia vary from less than 20 to almost 100 cases annually with 54-89 cases in recent years. A part of these cases (33 cases during the last 5 years) are alimentary infections after drinking of raw goat and sheep milk.

  19. Association Between Antibody Titers and Protection Against Influenza Virus Infection Within Households

    PubMed Central

    Tsang, Tim K.; Cauchemez, Simon; Perera, Ranawaka A. P. M.; Freeman, Guy; Fang, Vicky J.; Ip, Dennis K. M.; Leung, Gabriel M.; Malik Peiris, Joseph Sriyal; Cowling, Benjamin J.

    2014-01-01

    Background. Previous studies have established that antibody titer measured by the hemagglutination-inhibiting (HAI) assay is correlated with protection against influenza virus infection, with an HAI titer of 1:40 generally associated with 50% protection. Methods. We recruited index cases with confirmed influenza virus infection from outpatient clinics, and followed up their household contacts for 7–10 days to identify secondary infections. Serum samples collected from a subset of household contacts were tested by HAI and microneutralization (MN) assays against prevalent influenza viruses. We analyzed the data using an individual hazard-based transmission model that adjusted for age and vaccination history. Results. Compared to a reference group with antibody titers <1:10, we found that HAI titers of 1:40 against influenza A(H1N1) and A(H3N2) were associated with 31% (95% confidence interval [CI], 13%–46%) and 31% (CI, 1%–53%) protection against polymerase chain reaction (PCR)–confirmed A(H1N1) and A(H3N2) virus infection, respectively, while an MN titer of 1:40 against A(H3N2) was associated with 49% (95% CI, 7%–81%) protection against PCR-confirmed A(H3N2) virus infection. Conclusions. An HAI titer of 1:40 was associated with substantially less than 50% protection against PCR-confirmed influenza virus infection within households, perhaps because of exposures of greater duration or intensity in that confined setting. PMID:24676208

  20. Toscana Virus Encephalitis in a Traveler Returning to the United States

    PubMed Central

    Azar, Marwan M.; Landry, Marie L.; Shaw, Albert C.

    2015-01-01

    In Italy, Toscana virus is the most common cause of meningitis from May to October. Though only a few cases have been reported in U.S. travelers returning from Europe, most cases are likely unrecognized due to lack of familiarity with the disease. Here, we describe the case of an 82-year-old man presenting with fever, profound weakness, and hearing loss after returning to the United States following a 2-week summertime vacation in southern Italy who was ultimately diagnosed with Toscana virus encephalitis. This case should alert clinicians to the possibility of Toscana virus infection in returning travelers and provides information on how to obtain testing if Toscana virus is suspected. PMID:25673791

  1. Diagnosis of eastern equine encephalitis by immunohistochemistry in two flocks of Michigan ring-neck pheasants.

    PubMed

    Williams, S M; Fulton, R M; Patterson, J S; Reed, W M

    2000-01-01

    The diagnosis of eastern equine encephalitis (EEE) virus infection in avian species is relatively difficult when compared with other species. There are no characteristic histologic lesions in the avian brain that would serve to distinguish EEE from infections with, for example, Newcastle disease or highly pathogenic avian influenza virus. Traditionally, virus isolation (VI) and/or hemagglutination inhibition (HI) has been used for a definitive diagnosis of EEE in birds. Recently, we developed an immunohistochemistry (IHC) technique for confirmatory diagnosis of EEE infection in equine brain. This test also detected EEE virus in formalin-fixed avian brain. VI confirmed IHC finding in two cases of EEE in ring-neck pheasants. IHC is a rapid, sensitive test for confirming and differentiating a histopathologic diagnosis of EEE in avian species and should be considered as an alternative test to VI or HI.

  2. A case of encephalitis in a human associated with a serologic rise to Jamestown Canyon virus.

    PubMed

    Grimstad, P R; Shabino, C L; Calisher, C H; Waldman, R J

    1982-11-01

    An 8-year-old girl living in rural southwestern Michigan experienced sudden onset of symptoms beginning with headache, dizziness and fever which rapidly progressed to central nervous system involvement with seizures and coma. Following 27 days of hospitalization her recovery was uneventful, with no apparent sequelae 15 months after discharge. Serologic studies of paired sera showed a rise in antibody to Jamestown Canyon virus, a member of the California serogroup (family Bunyaviridae). Specific IgM anti-Jamestown Canyon virus antibody was detected in sera drawn 9 days after onset. A concomitant rise in complement fixation antibody to herpesvirus was also noted. We believe this is the first reported case of encephalitis associated with Jamestown Canyon virus infection. Reasons are presented for the current inability to routinely detect infection and clinical illness caused by this virus.

  3. Nationwide Distribution of Bovine Influenza D Virus Infection in Japan

    PubMed Central

    Horimoto, Taisuke; Hiono, Takahiro; Mekata, Hirohisa; Odagiri, Tomoha; Lei, Zhihao; Kobayashi, Tomoya; Norimine, Junzo; Inoshima, Yasuo; Hikono, Hirokazu; Murakami, Kenji; Sato, Reiichiro; Murakami, Hironobu; Sakaguchi, Masahiro; Ishii, Kazunori; Ando, Takaaki; Otomaru, Kounosuke; Ozawa, Makoto; Sakoda, Yoshihiro; Murakami, Shin

    2016-01-01

    Cattle are major reservoirs of the provisionally named influenza D virus, which is potentially involved in the bovine respiratory disease complex. Here, we conducted a serological survey for the influenza D virus in Japan, using archived bovine serum samples collected during 2010–2016 from several herds of apparently healthy cattle in various regions of the country. We found sero-positive cattle across all years and in all the prefectural regions tested, with a total positivity rate of 30.5%, although the positivity rates varied among regions (13.5–50.0%). There was no significant difference in positivity rates for Holstein and Japanese Black cattle. Positivity rates tended to increase with cattle age. The herds were clearly divided into two groups: those with a high positive rate and those with a low (or no) positive rate, indicating that horizontal transmission of the virus occurs readily within a herd. These data demonstrate that bovine influenza D viruses have been in circulation for at least 5 years countrywide, emphasizing its ubiquitous distribution in the cattle population of Japan. PMID:27682422

  4. Modulation of Innate Immunity by Copolymer-1 Leads to Neuroprotection in Murine HIV-1 Encephalitis

    PubMed Central

    Gorantla, Santhi; Liu, Jianuo; Wang, Tong; Holguin, Adelina; Sneller, Hannah M; Dou, Huanyu; Kipnis, Jonathan; Poluektova, Larisa; Gendelman, Howard E

    2009-01-01

    Virus-infected and immune competent mononuclear phagocytes (MP; perivascular macrophages and microglia) drive the neuropathogenesis of human immunodeficiency virus type one (HIV-1) infection. Modulation of the MP phenotype from neurodestructive to neuroprotective underlies adjunctive therapeutic strategies for human disease. We reasoned that, as Copolymer-1 (Cop-1) can induce neuroprotective activities in a number of neuroinflammatory and neurodegenerative disorders, it could directly modulate HIV-1 infected MP neurotoxic activities. We now demonstrate that, in laboratory assays, Cop-1-stimulated virus-infected human monocyte-derived macrophages protect against neuronal injury and elicit anti-retroviral activities. Severe combined immune deficient (SCID) mice were stereotactically injected with HIV-1 infected human monocyte-derived macrophages, into the basal ganglia, to induce HIV-1 encephalitis (HIVE). Cop-1 was administered subcutaneously for 7 days. In HIVE mice Cop-1 treatment led to anti-inflammatory and neuroprotective responses. Reduced micro- and astro- gliosis, and conserved NeuN/MAP-2 levels were observed in virus affected brain regions in Cop-1-treated mice. These were linked to interleukin-10 and brain-derived neurotrophic factor expression and downregulation of inducible nitric oxide synthase. The data, taken together, demonstrate that Cop-1 can modulate innate immunity and, as such, improve disease outcomes in an animal model of HIVE. PMID:18046731

  5. Acute influenza virus-associated encephalitis and encephalopathy in adults: a challenging diagnosis

    PubMed Central

    Linn, Francisca H. H.; Wensing, Anne M. J.; Leavis, Helen L.; van Riel, Debby; GeurtsvanKessel, Corine H.; Wattjes, Mike P.; Murk, Jean-Luc

    2016-01-01

    Background: Acute influenza-associated encephalopathy/encephalitis (IAE) in adults is a rare but well-known complication of influenza virus infection. The diagnosis is difficult to make due to the absence of distinctive clinical symptoms and validated diagnostic criteria. We present an illustrative case and a case review on acute IAE in adults. Methods: We performed a Medline search of the English literature using the terms influenz*, encephal* and adult, and constructed a database of detailed descriptions of patients with influenza virus infection with influenza-like symptoms at the onset of neurological symptoms. Results: A total of 44 patients were included. Confusion and seizures were the most prevalent neurological symptoms, present in 12 (27 %) and 10 (23 %) patients, respectively. Magnetic resonance imaging (MRI) was performed in 21 patients and anomalies were found in 13 (62 %), with lesions located throughout the brain. Influenza virus RNA was detected in cerebrospinal fluid (CSF) in 5 (16 %) of 32 patients. Eight (18 %) of the forty-four patients died. The benefits of antiviral and immunomodulatory therapy have not been well studied. Discussion: Our results show that many different neurological symptoms can be present in patients with acute onset IAE. Therefore, the diagnosis should be considered in patients with fever and neurological symptoms, especially during the influenza season. Laboratory diagnosis consists of demonstration of influenza virus RNA in brain tissue, CSF or respiratory samples, and demonstration of intrathecal antibody production against influenza virus. The presence of brain lesions in MRI and influenza virus in CSF appear to be of prognostic value. PMID:28348797

  6. Japanese language and Japanese science

    NASA Astrophysics Data System (ADS)

    Tanikawa, Kiyotaka

    2003-08-01

    Japanese mathematical scientists including astronomers, physicists, and mathematicians obtain ideas in Japanese, discuss their problems in Japanese, and arrive at conclusions in Japanese, and yet they write their results in foreign languages such as English. This uncomfortable situation has continued for nearly one hundred years and has had serious effects on Japanese science. In this short report, the author discusses and analyses these effects. In order to put Japanese science on a sound basis, the author proposes to increase the number of articles, reviews and textbooks in Japanese, first by translation and second by the voluntary efforts of scientists themselves. As centers devoted to this activity, the author proposes to construct "Airborne Libraries" which are maintained and accumulate in an electronic form the scientific documents written in Japanese.

  7. Japanese Competitiveness and Japanese Management.

    ERIC Educational Resources Information Center

    Minabe, Shigeo

    1986-01-01

    Analyzes and compares Japanese and American industrial policy and labor practices. Proposes that certain aspects of the Japanese system be adapted by American businesses for purpose of increasing international competitiveness. Proposes specific actions and plans for both the Japanese and American systems. (ML)

  8. Visual influences on primate encephalization.

    PubMed

    Kirk, E Christopher

    2006-07-01

    Primates differ from most other mammals in having relatively large brains. As a result, numerous comparative studies have attempted to identify the selective variables influencing primate encephalization. However, none have examined the effect of the total amount of visual input on relative brain size. According to Jerison's principle of proper mass, functional areas of the brain devoted primarily to processing visual information should exhibit increases in size when the amount of visual input to those areas increases. As a result, the total amount of visual input to the brain could exert a large influence on encephalization because visual areas comprise a large proportion of total brain mass in primates. The goal of this analysis is to test the expectation of a direct relationship between visual input and encephalization using optic foramen size and optic nerve size as proxies for total visual input. Data were collected for a large comparative sample of primates and carnivorans, and three primary analyses were undertaken. First, the relationship between relative proxies for visual input and relative endocranial volume were examined using partial correlations and phylogenetic comparative methods. Second, to examine the generality of the results derived for extant primates, a parallel series of partial correlation and comparative analyses were undertaken using data for carnivorans. Third, data for various Eocene and Oligocene primates were compared with those for living primates in order to determine whether the fossil taxa demonstrate a similar relationship between relative brain size and visual input. All three analyses confirm the expectations of proper mass and favor the conclusion that the amount of visual input has been a major influence on the evolution of relative brain size in both primates and carnivorans. Furthermore, this study suggests that differences in visual input may partly explain (1) the high encephalization of primates relative to the primitive

  9. Mouse Hepatitis Virus Infection Remodels Connexin43-Mediated Gap Junction Intercellular Communication In Vitro and In Vivo

    PubMed Central

    Basu, Rahul; Banerjee, Kaveri; Bose, Abhishek

    2015-01-01

    ABSTRACT Gap junctions (GJs) form intercellular channels which directly connect the cytoplasm between neighboring cells to facilitate the transfer of ions and small molecules. GJs play a major role in the pathogenesis of infection-associated inflammation. Mutations of gap junction proteins, connexins (Cxs), cause dysmyelination and leukoencephalopathy. In multiple sclerosis (MS) patients and its animal model experimental autoimmune encephalitis (EAE), Cx43 was shown to be modulated in the central nervous system (CNS). The mechanism behind Cx43 alteration and its role in MS remains unexplored. Mouse hepatitis virus (MHV) infection-induced demyelination is one of the best-studied experimental animal models for MS. Our studies demonstrated that MHV infection downregulated Cx43 expression at protein and mRNA levels in vitro in primary astrocytes obtained from neonatal mouse brains. After infection, a significant amount of Cx43 was retained in endoplasmic reticulum/endoplasmic reticulum Golgi intermediate complex (ER/ERGIC) and GJ plaque formation was impaired at the cell surface, as evidenced by a reduction of the Triton X-100 insoluble fraction of Cx43. Altered trafficking and impairment of GJ plaque formation may cause the loss of functional channel formation in MHV-infected primary astrocytes, as demonstrated by a reduced number of dye-coupled cells after a scrape-loading Lucifer yellow dye transfer assay. Upon MHV infection, a significant downregulation of Cx43 was observed in the virus-infected mouse brain. This study demonstrates that astrocytic Cx43 expression and function can be modulated due to virus stress and can be an appropriate model to understand the basis of cellular mechanisms involved in the alteration of gap junction intercellular communication (GJIC) in CNS neuroinflammation. IMPORTANCE We found that MHV infection leads to the downregulation of Cx43 in vivo in the CNS. In addition, results show that MHV infection impairs Cx43 expression in addition

  10. 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

  11. Kinetic study of platelets and fibrinogen in Lassa virus-infected monkeys and early pathologic events in Mopeia virus-infected monkeys.

    PubMed

    Lange, J V; Mitchell, S W; McCormick, J B; Walker, D H; Evatt, B L; Ramsey, R R

    1985-09-01

    The rhesus monkey, an established model of Lassa fever, was used to study hematologic and hemostatic aspects of Lassa fever and whether Mopeia (also known as Mozambique) virus induces any cellular damage in this model. Six days after subcutaneous injection of 10(3.48) plaque forming units (PFU) of Lassa virus (Josiah strain) one group of monkeys received an intravenous injection of 111In-labeled allogeneic platelets and another group received 125I-labeled alogeneic fibrinogen. Lassa virus-infected monkeys developed a severe clinical illness with high viremia and typical pathology. Lassa antigen was found in most tissues using a Lassa nucleocapsid-specific monoclonal antibody. Platelet counts remained within normal limits. Platelet and fibrinogen kinetics were similar in infected and control animals. Hematologic and hemostatic changes indicate that disseminated intravascular coagulation plays no role in this model of Lassa fever. Levels of plasma fibronectin were reduced in Lassa-infected monkeys. Mopeia virus-infected monkeys were normothemic, aviremic, and there was no detection of Mopeia antigen in any tissues using polyclonal or monoclonal antibodies. Mopeia virus was recovered from the spleen of one monkey. Mopeia virus was associated with hepatocellular and renal tubular damage.

  12. Severe cutaneous human papilloma virus infection associated with Natural Killer cell deficiency following stem cell transplantation for severe combined immunodeficiency

    PubMed Central

    Kamili, Qurat-ul-Ain; Seeborg, Filiz O; Saxena, Kapil; Nicholas, Sarah K; Banerjee, Pinaki P; Angelo, Laura S; Mace, Emily M; Forbes, Lisa R; Martinez, Caridad; Wright, Teresa S; Orange, Jordan S.; Hanson, Imelda Celine

    2016-01-01

    Capsule Summary The authors identify Natural Killer cell deficiency in post-transplant severe combined immunodeficiency patients who developed severe human papilloma virus infections as a long term complication. PMID:25159470

  13. Matters of Size: Genetic Bottlenecks in Virus Infection and Their Potential Impact on Evolution.

    PubMed

    Zwart, Mark P; Elena, Santiago F

    2015-11-01

    For virus infections of multicellular hosts, narrow genetic bottlenecks during transmission and within-host spread appear to be widespread. These bottlenecks will affect the maintenance of genetic variation in a virus population and the prevalence of mixed-strain infections, thereby ultimately determining the strength with which different random forces act during evolution. Here we consider different approaches for estimating bottleneck sizes and weigh their merits. We then review quantitative estimates of bottleneck size during cellular infection, within-host spread, horizontal transmission, and finally vertical transmission. In most cases we find that bottlenecks do regularly occur, although in many cases they appear to be virion-concentration dependent. Finally, we consider the evolutionary implications of genetic bottlenecks during virus infection. Although on average strong bottlenecks will lead to declines in fitness, we consider a number of scenarios in which bottlenecks could also be advantageous for viruses.

  14. Imported zika virus infection from the cook islands into australia, 2014.

    PubMed

    Pyke, Alyssa T; Daly, Michelle T; Cameron, Jane N; Moore, Peter R; Taylor, Carmel T; Hewitson, Glen R; Humphreys, Jan L; Gair, Richard

    2014-06-02

    A female resident of Townsville, Queensland, Australia has been diagnosed with Zika virus infection following a recent trip to the Cook Islands. An initial serum sample collected in March, 2014 was positive by two separate Zika virus TaqMan real-time RT-PCRs and a pan-Flavivirus RT-PCR. Nucleotide sequencing and phylogenetics of the complete Cook Islands Zika virus envelope gene revealed 99.1% homology with a previous Cambodia 2010 sequence within the Asian lineage. In addition, IgG and IgM antibody seroconversions were detected between paired acute and convalescent phase sera using recombinant Zika virus serology assays. This is the first known imported case of Zika virus infection into northern Queensland where the potential mosquito vector Aedes aegypti is present and only the second such reported case diagnosed within Australia.

  15. Toll-like receptor 4 polymorphisms in dengue virus-infected children.

    PubMed

    Djamiatun, Kis; Ferwerda, Bart; Netea, Mihai G; van der Ven, André J A M; Dolmans, Wil M V; Faradz, Sultana M H

    2011-08-01

    Differential viral recognition by cells bearing Toll-like receptor 4 (TLR4) polymorphisms Asp299Gly and Thr399Ile may influence susceptibility and severity of dengue virus infection. In central Java, Indonesia, we investigated 201 children with dengue hemorrhagic fever (DHF) and 179 healthy controls. Patients and controls were mostly ethnic Javanese. A nearly complete cosegregation of the two mutations was observed. The TLR4 299/399 genotype was found in five patients and four controls. Prevalence of the TLR4 299/399 genotype did not differ significantly between controls and DHF patients or between patients with different severities of DHF. Also, vascular leakage in patients with different TLR4 genotypes did not differ. Thus, the 299/399 TLR4 haplotype has only minor influence on susceptibility and severity of complicated dengue virus infection.

  16. Worldwide occurrence of virus-infections in filamentous marine brown algae

    NASA Astrophysics Data System (ADS)

    Müller, D. G.; Stache, B.

    1992-03-01

    Virus infections were detected in Ectocarpus siliculosus and Ectocarpus fasciculatus on the coasts of Ireland, California, Peru, southern South America, Australia and New Zealand; in three Feldmannia species on the coasts of Ireland, continental Chile and Archipelago Juan Fernandez (Chile); and in Leptonematella from Antarctica. Natural populations on the Irish coast contained 3% infected plants in E. fasciculatus, and less than 1% in Feldmannia simplex. On the Californian coast, 15 to 25% of Ectocarpus isolates were infected. Virus symptoms were absent in E. siliculosus from Peru, but appeared after meiosis in laboratory cultures. The virus particles in E. fasciculatus are identical in size and capsid structure to those reported for E. siliculosus, while the virus in F. simplex is smaller and has a different envelope. Our findings suggest that virus infections are a common and worldwide phenomenon in filamentous brown algae.

  17. Zika virus infection during the Olympic Games in Rio: A fear or an actual risk?

    PubMed

    Díaz-Menéndez, M; Trigo, E; de la Calle-Prieto, F; Arsuaga, M

    2017-04-01

    The recent outbreak of Zika virus infection in Brazil has aroused considerable media interest due to its association with neurological malformations in children born from mothers infected by the virus and to its association with Guillain-Barre syndrome in adults. This relationship has led to the World Health Organisation declaring the current epidemic as a "Public Health Emergency of International Concern". Controversy also emerged on the advisability of delaying or changing the location of the Olympic and Paralympic Games, which were held in August at various locations in Brazil. In this article, we review the available evidence on the risk of Zika and dengue virus infection in individuals who travel to endemic countries, especially for multitudinous events.

  18. A cluster of Zika virus infection in a Chinese tour group returning from Fiji and Samoa

    PubMed Central

    Sun, Jimin; Fu, Tao; Mao, Haiyan; Wang, Zhen; Pan, Junhang; Rutherford, Shannon; Ren, Jiangping; Dong, Xuanjun; Chen, Yin; Zhu, Zhihong; Qi, Xiaohua; Gong, Zhenyu; Liu, Qiyong; Yu, Hongjie; Zhu, Liebo; Chen, Wenxian; Chen, Zhiping; Zhang, Yanjun; Chen, Enfu

    2017-01-01

    Zika virus is currently causing extensive outbreaks in a number of countries in South and Central America and the Caribbean and has been associated with foetal abnormalities. We report an outbreak of Zika virus infection in a Chinese tour-group returning from a nine day holiday in Fiji and Samoa. The index case was a 38-year old male who developed symptoms while travelling back from Fiji to Hong Kong on the 14th February, 2016. A field investigation was initiated to define the epidemiological, clinical and virological characteristics of Zika virus infection in this tour group and revealed two further symptomatic infections and one asymptomatic infection among the 33 travellers; an overall infection attack rate of 12% in these travellers. Active surveillance led to detection of Zika virus RNA in the serum of one case four days prior to onset of symptoms and detection of Zika virus in saliva from one asymptomatic infection.

  19. Vitamin D-Regulated MicroRNAs: Are They Protective Factors against Dengue Virus Infection?

    PubMed Central

    Arboleda, John F.; Urcuqui-Inchima, Silvio

    2016-01-01

    Over the last few years, an increasing body of evidence has highlighted the critical participation of vitamin D in the regulation of proinflammatory responses and protection against many infectious pathogens, including viruses. The activity of vitamin D is associated with microRNAs, which are fine tuners of immune activation pathways and provide novel mechanisms to avoid the damage that arises from excessive inflammatory responses. Severe symptoms of an ongoing dengue virus infection and disease are strongly related to highly altered production of proinflammatory mediators, suggesting impairment in homeostatic mechanisms that control the host's immune response. Here, we discuss the possible implications of emerging studies anticipating the biological effects of vitamin D and microRNAs during the inflammatory response, and we attempt to extrapolate these findings to dengue virus infection and to their potential use for disease management strategies. PMID:27293435

  20. Prevalence of occult hepatitis B virus infection in kidney transplant recipients

    PubMed Central

    Franz, Cibele; Perez, Renata de Mello; Zalis, Mariano Gustavo; Zalona, Ana Carolina Jonard; Rocha, Pedro Túlio Monteiro de Castro e Abreu; Gonçalves, Renato Torres; Nabuco, Letícia Cancella; Villela-Nogueira, Cristiane Alves

    2013-01-01

    In this cross-sectional study, 207 hepatitis B surface antigen (HBsAg)-negative kidney transplant recipients were evaluated based on demographic and epidemiological data and on the levels of serological markers of hepatitis B virus (HBV) and hepatitis C virus infection and liver enzymes. Patients with HBV or human immunodeficiency virus infection were excluded. Sera were analysed for the presence of HBV-DNA. HBV-DNA was detected in two patients (1%), indicating occult hepatitis B (OHB) infection (the HBV-DNA loads were 3.1 and 3.5 IU/mL in these patients). The results of the liver function tests were normal and no serological markers indicative of HBV infection were detected. The prevalence of OHB infection was low among kidney transplant recipients, most likely due to the low HBsAg endemicity in the general population of the study area. PMID:23903984

  1. Cell autonomous regulation of herpes and influenza virus infection by the circadian clock

    PubMed Central

    Edgar, Rachel S.; Stangherlin, Alessandra; Nagy, Andras D.; Nicoll, Michael P.; Efstathiou, Stacey; O’Neill, John S.; Reddy, Akhilesh B.

    2016-01-01

    Viruses are intracellular pathogens that hijack host cell machinery and resources to replicate. Rather than being constant, host physiology is rhythmic, undergoing circadian (∼24 h) oscillations in many virus-relevant pathways, but whether daily rhythms impact on viral replication is unknown. We find that the time of day of host infection regulates virus progression in live mice and individual cells. Furthermore, we demonstrate that herpes and influenza A virus infections are enhanced when host circadian rhythms are abolished by disrupting the key clock gene transcription factor Bmal1. Intracellular trafficking, biosynthetic processes, protein synthesis, and chromatin assembly all contribute to circadian regulation of virus infection. Moreover, herpesviruses differentially target components of the molecular circadian clockwork. Our work demonstrates that viruses exploit the clockwork for their own gain and that the clock represents a novel target for modulating viral replication that extends beyond any single family of these ubiquitous pathogens. PMID:27528682

  2. Viral myocarditis: potential defense mechanisms within the cardiomyocyte against virus infection

    PubMed Central

    Yajima, Toshitaka

    2011-01-01

    Virus infection can inflict significant damage on cardiomyocytes through direct injury and secondary immune reactions, leading to myocarditis and dilated cardiomyopathy. While viral myocarditis or cardiomyopathy is a complication of systemic infection of cardiotropic viruses, most individuals infected with the viruses do not develop significant cardiac disease. However, some individuals proceed to develop severe virus-mediated heart disease. Recent studies have shown that viral infection of cardiomyocytes is required for the development of myocarditis and subsequent cardiomyopathy. This suggests that viral infection of cardiomyocytes can be an important step that determines the pathogenesis of viral myocarditis during systemic infection. Accordingly, this article focuses on potential defense mechanisms within the cardiomyocyte against virus infection. Understanding of the cardiomyocyte defense against invading viruses may give us novel insights into the pathophysiology of viral myocarditis, and enable us to develop innovative strategies of diagnosis and treatment for this challenging clinical entity. PMID:21585262

  3. Reactivation of latent herpes simplex virus infection by ultraviolet light: a human model

    SciTech Connect

    Perna, J.J.; Mannix, M.L.; Rooney, J.F.; Notkins, A.L.; Straus, S.E.

    1987-09-01

    Infection with herpes simplex virus often results in a latent infection of local sensory ganglia and a disease characterized by periodic viral reactivation and mucocutaneous lesions. The factors that trigger reactivation in humans are still poorly defined. In our study, five patients with documented histories of recurrent herpes simplex virus infection on the buttocks or sacrum were exposed to three times their minimal erythema dose of ultraviolet light. Site-specific cutaneous herpes simplex virus infection occurred at 4.4 +/- 0.4 days after exposure to ultraviolet light in 8 of 13 attempts at reactivation. We conclude that ultraviolet light can reactivate herpes simplex virus under experimentally defined conditions. This model in humans should prove useful in evaluating the pathophysiology and prevention of viral reactivation.

  4. Innate lymphoid cells promote lung tissue homeostasis following acute influenza virus infection

    PubMed Central

    Monticelli, Laurel A.; Sonnenberg, Gregory F.; Abt, Michael C.; Alenghat, Theresa; Ziegler, Carly G.K.; Doering, Travis A.; Angelosanto, Jill M.; Laidlaw, Brian J.; Yang, Cliff Y.; Sathaliyawala, Taheri; Kubota, Masaru; Turner, Damian; Diamond, Joshua M.; Goldrath, Ananda W.; Farber, Donna L.; Collman, Ronald G.; Wherry, E. John; Artis, David

    2012-01-01

    Innate lymphoid cells (ILCs), a recently identified heterogeneous cell population, are critical in orchestrating immunity and inflammation in the intestine but whether ILCs can influence immune responses or tissue homeostasis at other mucosal sites remains poorly characterized. Here we identify a population of lung-resident ILCs in mice and humans that expressed CD90, CD25, CD127 and T1-ST2. Strikingly, mouse ILCs accumulated in the lung following influenza virus infection and depletion of ILCs resulted in loss of airway epithelial integrity, decreased lung function and impaired airway remodeling. These defects could be restored by administration of the lung ILC product amphiregulin. Collectively, these results demonstrate a critical role for lung ILCs in restoring airway epithelial integrity and tissue homeostasis following influenza virus infection. PMID:21946417

  5. Within-host spatiotemporal dynamics of plant virus infection at the cellular level.

    PubMed

    Tromas, Nicolas; Zwart, Mark P; Lafforgue, Guillaume; Elena, Santiago F

    2014-02-01

    A multicellular organism is not a monolayer of cells in a flask; it is a complex, spatially structured environment, offering both challenges and opportunities for viruses to thrive. Whereas virus infection dynamics at the host and within-cell levels have been documented, the intermediate between-cell level remains poorly understood. Here, we used flow cytometry to measure the infection status of thousands of individual cells in virus-infected plants. This approach allowed us to determine accurately the number of cells infected by two virus variants in the same host, over space and time as the virus colonizes the host. We found a low overall frequency of cellular infection (<0.3), and few cells were coinfected by both virus variants (<0.1). We then estimated the cellular contagion rate (R), the number of secondary infections per infected cell per day. R ranged from 2.43 to values not significantly different from zero, and generally decreased over time. Estimates of the cellular multiplicity of infection (MOI), the number of virions infecting a cell, were low (<1.5). Variance of virus-genotype frequencies increased strongly from leaf to cell levels, in agreement with a low MOI. Finally, there were leaf-dependent differences in the ease with which a leaf could be colonized, and the number of virions effectively colonizing a leaf. The modeling of infection patterns suggests that the aggregation of virus-infected cells plays a key role in limiting spread; matching the observation that cell-to-cell movement of plant viruses can result in patches of infection. Our results show that virus expansion at the between-cell level is restricted, probably due to the host environment and virus infection itself.

  6. A20 Deficiency in Lung Epithelial Cells Protects against Influenza A Virus Infection

    PubMed Central

    Vereecke, Lars; Mc Guire, Conor; Sze, Mozes; Schuijs, Martijn J.; Willart, Monique; Itati Ibañez, Lorena; Hammad, Hamida; Lambrecht, Bart N.; Beyaert, Rudi; Saelens, Xavier; van Loo, Geert

    2016-01-01

    A20 negatively regulates multiple inflammatory signalling pathways. We here addressed the role of A20 in club cells (also known as Clara cells) of the bronchial epithelium in their response to influenza A virus infection. Club cells provide a niche for influenza virus replication, but little is known about the functions of these cells in antiviral immunity. Using airway epithelial cell-specific A20 knockout (A20AEC-KO) mice, we show that A20 in club cells critically controls innate immune responses upon TNF or double stranded RNA stimulation. Surprisingly, A20AEC-KO mice are better protected against influenza A virus challenge than their wild type littermates. This phenotype is not due to decreased viral replication. Instead host innate and adaptive immune responses and lung damage are reduced in A20AEC-KO mice. These attenuated responses correlate with a dampened cytotoxic T cell (CTL) response at later stages during infection, indicating that A20AEC-KO mice are better equipped to tolerate Influenza A virus infection. Expression of the chemokine CCL2 (also named MCP-1) is particularly suppressed in the lungs of A20AEC-KO mice during later stages of infection. When A20AEC-KO mice were treated with recombinant CCL2 the protective effect was abrogated demonstrating the crucial contribution of this chemokine to the protection of A20AEC-KO mice to Influenza A virus infection. Taken together, we propose a mechanism of action by which A20 expression in club cells controls inflammation and antiviral CTL responses in response to influenza virus infection. PMID:26815999

  7. Retention of Fluorescent Antigenicity of Virus-Infected Cells on Spotslides under Various Conditions of Storage

    DTIC Science & Technology

    1982-08-19

    indicate that RVF and PIC viruses are stable at both 4 and -200C for up to 365 days. TCR virus is stable for 123 days at both 4 and -200C, and then...Journal of Virological Methods, 5 (1982) 279- 284 279 !Elsevier Biomedical Press I RETENTION OF FLUORESCENT ANTIGENICITY OF VIRUS -INFECTED CELLS ON...hemorrhagic fever (KHF, French et al., 1980) viruses . One of the primary problems (other than the subjectivity of interpretation) associated with the

  8. Fungal DNA virus infects a mycophagous insect and utilizes it as a transmission vector

    PubMed Central

    Liu, Si; Xie, Jiatao; Cheng, Jiasen; Li, Bo; Chen, Tao; Fu, Yanping; Li, Guoqing; Wang, Manqun; Jin, Huanan; Wan, Hu; Jiang, Daohong

    2016-01-01

    Mycoviruses are usually transmitted horizontally via hyphal anastomosis and vertically via sexual/asexual spores. Previously, we reported that a gemycircularvirus, Sclerotinia sclerotiorum hypovirulence-associated DNA virus 1 (SsHADV-1), could infect its fungal host extracellularly. Here, we discovered that SsHADV-1 could infect a mycophagous insect, Lycoriella ingenua, and use it as a transmission vector. Virus acquired by larvae feeding on colonies of a virus-infected strain of S. sclerotiorum was replicated and retained in larvae, pupae, adults, and eggs. Virus could be transmitted to insect offspring when larvae were injected with virus particles and allowed to feed on a nonhost fungus. Virus replication in insect cells was further confirmed by inoculating Spodoptera frugiperda cells with virus particles and analyzing with RT-PCR, Northern blot, immunofluorescence, and flow cytometry assays. Larvae could transmit virus once they acquired virus by feeding on virus-infected fungal colony. Offspring larvae hatched from viruliferous eggs were virus carriers and could also successfully transmit virus. Virus transmission between insect and fungus also occurred on rapeseed plants. Virus-infected isolates produced less repellent volatile substances to attract adults of L. ingenua. Furthermore, L. ingenua was easily observed on Sclerotinia lesions in rapeseed fields, and viruliferous adults were captured from fields either sprayed with a virus-infected fungal strain or nonsprayed. Our findings may facilitate the exploration of mycoviruses for control of fungal diseases and enhance our understanding of the ecology of SsHADV-1 and other newly emerging SsHADV-1–like viruses, which were recently found to be widespread in various niches including human HIV-infected blood, human and animal feces, insects, plants, and even sewage. PMID:27791095

  9. Lassa Virus Infection of Rhesus Monkeys: Pathogenesis and Treatment with Ribavirin

    DTIC Science & Technology

    1980-05-01

    viruses [5, 61, is effective in treating severe The views of the authors do not purport to reflect the posi- Lassa virus disease in rhesus monkeys...THE JOURNAL OF INFECTIOUS DISEASES - VOL. 141, NO. 5 MAY 1980 1980 by The University of Chicago. 0022-1899/80/410500 .95 ECr C- Lassa Virus Infection...Atlanta, Georgia Rhesus monkeys were experimentally infected with Lassa virus to establish their suita- bility as a nonhuman primate model for the human

  10. Epidermodysplasia verruciformis associated with plasmablastic lymphoma and hepatitis B virus infection.

    PubMed

    Shayanfar, Nasrin; Babaheidarian, Pegah; Rahmani, Hoda; Azadmanesh, Keyhan; Sohrabi, Amir; Mohammadpour, Masoud; Mirzaie, Ali Zare; Parvaneh, Nima

    2012-01-01

    Epidermodysplasia verruciformis is a rare genodermatosis characterized by inherited susceptibility to infection with certain papillomaviruses, which leads to the development of disseminated plane wart-like lesions. In some patients, lesions resembling pityriasis versicolor appear. Epidermodysplasia verruciformis has also been reported in immunosuppressed patients, most notably those with HIV infection. The affected patients are predisposed to development of skin and mucosal malignancies. We describe the rare occurrence of plasmablastic lymphoma in a patient with long lasting epidermodysplasia verruciformis and hepatitis B virus infection.

  11. Within-Host Spatiotemporal Dynamics of Plant Virus Infection at the Cellular Level

    PubMed Central

    Lafforgue, Guillaume; Elena, Santiago F.

    2014-01-01

    A multicellular organism is not a monolayer of cells in a flask; it is a complex, spatially structured environment, offering both challenges and opportunities for viruses to thrive. Whereas virus infection dynamics at the host and within-cell levels have been documented, the intermediate between-cell level remains poorly understood. Here, we used flow cytometry to measure the infection status of thousands of individual cells in virus-infected plants. This approach allowed us to determine accurately the number of cells infected by two virus variants in the same host, over space and time as the virus colonizes the host. We found a low overall frequency of cellular infection (<0.3), and few cells were coinfected by both virus variants (<0.1). We then estimated the cellular contagion rate (R), the number of secondary infections per infected cell per day. R ranged from 2.43 to values not significantly different from zero, and generally decreased over time. Estimates of the cellular multiplicity of infection (MOI), the number of virions infecting a cell, were low (<1.5). Variance of virus-genotype frequencies increased strongly from leaf to cell levels, in agreement with a low MOI. Finally, there were leaf-dependent differences in the ease with which a leaf could be colonized, and the number of virions effectively colonizing a leaf. The modeling of infection patterns suggests that the aggregation of virus-infected cells plays a key role in limiting spread; matching the observation that cell-to-cell movement of plant viruses can result in patches of infection. Our results show that virus expansion at the between-cell level is restricted, probably due to the host environment and virus infection itself. PMID:24586207

  12. Identification of a Putative Coreceptor on Vero Cells That Participates in Dengue 4 Virus Infection

    PubMed Central

    Martínez-Barragán, José de Jesús; del Angel, Rosa M.

    2001-01-01

    Dengue virus infects target cells by attaching to a cell surface receptor through the envelope (E) glycoprotein, located on the surface of the viral membrane. On Vero and BHK cells, heparan sulfate (HS) moieties of proteoglycans are the receptors for dengue virus; however, additional proteins have also been described as putative dengue virus receptors on C6/36, HL60, and BM cells. HS can also act as a receptor for other types of viruses or as an attachment molecule for viruses that require additional host cell molecules to allow viral penetration. In this study we searched for molecules other than HS that could participate in dengue virus infection of Vero cells. Labeled dengue 4 virus bound with high affinity to two molecules of 74 and 44 kDa. Binding of dengue virus to the 74-kDa molecule was susceptible to protease and sodium periodate treatment and resistant to heparinase treatments. Lectins such as concanavalin A and wheat germ agglutinin prevented dengue virus binding to both the 74- and the 44-kDa protein in overlay assays, while phytohemagglutinin P did not affect binding, suggesting that carbohydrate residues (α-mannose or N-acetylglucosamine) are important in virus binding to host cells. Protease susceptibility, biotin labeling, and immunofluorescence with a polyclonal antibody raised against the 74-kDa protein consistently identified the protein on the surfaces of Vero cells. Moreover, the antibody against the 74-kDa protein was able to inhibit dengue virus infection. These data suggest that HS might serve as a primary receptor, probably concentrating virus particles on the surfaces of Vero cells, and then other molecules, such as the 74-kDa protein, might participate as coreceptors in viral penetration. The 74-kDa protein possibly constitutes part of a putative receptor complex for dengue virus infection of Vero cells. PMID:11483725

  13. Cowpox virus infection associated with a streptococcal septicaemia in a foal.

    PubMed

    Ellenberger, C; Schüppel, K-F; Möhring, M; Reischauer, A; Alex, M; Czerny, C-P; Fercho, A; Schoon, H-A

    2005-01-01

    Cowpox virus infection associated with a streptococcal septicaemia was diagnosed in a weak German Warmblood filly, born 29 days prematurely, and humanely destroyed on the sixth day of life. At necropsy, ulcerative lesions in the alimentary tract, colitis, polyarthritis and nephritis were observed. Transmission electron microscopical examination of specimens from ulcerative lesions revealed typical orthopox virions. Cowpox virus was unequivocally identified by virological and molecular-biological methods.

  14. EFFECTS OF ALLERGIC AIRWAYS DISEASE ON INFLUENZA VIRUS INFECTION IN BROWN NORWAY RATS

    EPA Science Inventory

    EFFECTS OF ALLERGIC AIRWAYS DISEASE ON INFLUENZA VIRUS INFECTION IN BROWN NORWAY RATS (P. Singhl, D.W. Winsett2, M.J. Daniels2,
    C.A.J. Dick', K.B. Adlerl and M.I. Gilmour2, INCSU, Raleigh, N.C., 2NHEERL/ORD/ USEPA, RTP, N.C. and 3UNC, Chapel Hill, N.C.)The interaction between ...

  15. Role of Mononuclear Phagocytes in the Pathogenesis of Human Immunodeficiency Virus Infection

    DTIC Science & Technology

    1990-01-01

    IMMUNODEFICIENCY VIRUS INFECTION1 Monte S. Meltzer , Donald R. Skillman,* Peter J. Gomatos, D. Chester Kalter,t and Howard E. Gendelmant HIV Immunopathogenesis...unlimited. ’ 170 MELTZER ET AL certain bodily tissues, such as those of the central nervous system, lymph nodes, or lung, the frequency of HIV-infected...172 MELTZER ET AL with interferon y (IFNy) or with bacterial endotoxic lipopolysaccharides were similar to those induced in control cells (24

  16. Zika virus infection in a traveller returning to Europe from Brazil, March 2015.

    PubMed

    Zammarchi, L; Tappe, D; Fortuna, C; Remoli, M E; Günther, S; Venturi, G; Bartoloni, A; Schmidt-Chanasit, J

    2015-06-11

    We report a case of laboratory-confirmed Zika virus infection imported into Europe from the Americas. The patient developed fever, rash, and oedema of hands and feet after returning to Italy from Brazil in late March 2015. The case highlights that, together with chikungunya virus and dengue virus, three major arboviruses are now co-circulating in Brazil. These arboviruses represent a burden for the healthcare systems in Brazil and other countries where competent mosquito vectors are present.

  17. ZIKA VIRUS INFECTION IN AUSTRALIA FOLLOWING A MONKEY BITE IN INDONESIA.

    PubMed

    Leung, Grace H Y; Baird, Robert W; Druce, Julian; Anstey, Nicholas M

    2015-05-01

    A traveller returning to Australia developed Zika virus infection, with fever, rash and conjunctivitis, with onset five days after a monkey bite in Bali, Indonesia. Flavivirus RNA detected on PCR from a nasopharyngeal swab was sequenced and identified as Zika virus. Although mosquito-borne transmission is also possible, we propose the bite as a plausible route of transmission. The literature for non-vector transmissions of Zika virus and other flaviviruses is reviewed.

  18. Susceptibility of bone marrow-derived macrophages to influenza virus infection is dependent on macrophage phenotype.

    PubMed

    Campbell, Gillian M; Nicol, Marlynne Q; Dransfield, Ian; Shaw, Darren J; Nash, Anthony A; Dutia, Bernadette M

    2015-10-01

    The role of the macrophage in influenza virus infection is complex. Macrophages are critical for resolution of influenza virus infections but implicated in morbidity and mortality in severe infections. They can be infected with influenza virus and consequently macrophage infection is likely to have an impact on the host immune response. Macrophages display a range of functional phenotypes, from the prototypical pro-inflammatory classically activated cell to alternatively activated anti-inflammatory macrophages involved in immune regulation and wound healing. We were interested in how macrophages of different phenotype respond to influenza virus infection and therefore studied the infection of bone marrow-derived macrophages (BMDMs) of classical and alternative phenotype in vitro. Our results show that alternatively activated macrophages are more readily infected and killed by the virus than classically activated. Classically activated BMDMs express the pro-inflammatory markers inducible nitric oxide synthase (iNOS) and TNF-α, and TNF-α expression was further upregulated following infection. Alternatively activated macrophages express Arginase-1 and CD206; however, following infection, expression of these markers was downregulated whilst expression of iNOS and TNF-α was upregulated. Thus, infection can override the anti-inflammatory state of alternatively activated macrophages. Importantly, however, this results in lower levels of pro-inflammatory markers than those produced by classically activated cells. Our results showed that macrophage phenotype affects the inflammatory macrophage response following infection, and indicated that modulating the macrophage phenotype may provide a route to develop novel strategies to prevent and treat influenza virus infection.

  19. Immunosuppression-Induced Susceptibility of Inbred Hamsters (Mesocricetus auratus) to Lethal-Disease by Lymphocytic Choriomeningitis Virus Infection

    DTIC Science & Technology

    1987-01-01

    and in human , , Lassa fever virus infections [20]. The role of antibody in recovery from infections with viruses such as LCMV. Lassa . and Pichinde...is not clear. Certainly the appearance of antibodies measured by IFAT in the LCMV-infected hamster or in Lassa .-. - fever virus infections [17. 19...Lvmphocvtit choriomeninEzitis virus and other arenaviruses . Springer. Berlin Heidelber New York. pp 113-120 9. Gee SR. Chan MA. (lark DA. Rawls WE (1981

  20. Announcement: Guidance for U.S. Laboratory Testing for Zika Virus Infection: Implications for Health Care Providers.

    PubMed

    2016-11-25

    CDC has released updated guidance online for U.S. laboratory testing for Zika virus infection. The guidance is available at https://www.cdc.gov/zika/laboratories/lab-guidance.html. Frequently asked questions are addressed at https://www.cdc.gov/zika/laboratories/lab-guidance-faq.html. This guidance updates recommendations for testing of specimens by U.S. laboratories for possible Zika virus infection. Major updates to the guidance with clinical implications for health care providers include the following.