Science.gov

Sample records for recombinant japanese encephalitis

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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

  6. 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 ...

  7. 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

  8. 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

  9. 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 ...

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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 ...

  7. 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

  8. 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.

  9. 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...

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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...

  17. 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

  18. 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...

  19. 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.

  20. 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

  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. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. Japanese encephalitis vaccines: current vaccines and future prospects.

    PubMed

    Monath, T P

    2002-01-01

    Vaccination against JE ideally should be practiced in all areas of Asia where the virus is responsible for human disease. The WHO has placed a high priority on the development of a new vaccine for prevention of JE. Some countries in Asia (Japan, South Korea, North Korea, Taiwan, Vietnam, Thailand, and the PRC) manufacture JE vaccines and practice childhood immunization, while other countries suffering endemic or epidemic disease (India, Nepal, Laos, Cambodia, Bangladesh, Myanmar, Malaysia, Indonesia and the Philippines) have no JE vaccine manufacturing or policy for use. With the exception of the PRC, all countries practicing JE vaccination use formalin inactivated mouse brain vaccines, which are relatively expensive and are associated with rare but clinically significant allergic and neurological adverse events. New inactivated JE vaccines manufactured in Vero cells are in advanced preclinical or early clinical development in Japan, South Korea, Taiwan, and the PRC. An empirically derived, live attenuated vaccine (SA14-14-2) is widely used in the PRC. Trials in the PRC have shown SA14-14-2 to be safe and effective when administered in a two-dose regimen, but regulatory concerns over manufacturing and control have restricted international distribution. The genetic basis of attenuation of SA14-14-2 has been partially defined. A new live attenuated vaccine (ChimeriVax-JE) that uses a reliable flavivirus vaccine--yellow fever 17D--as a live vector for the envelope genes of SA14-14-2 virus is in early clinical trials and appears to be well tolerated and immunogenic after a single dose. Vaccinia and avipox vectored vaccines have also been tested clinically, but are no longer being pursued due to restricted effectiveness mediated by anti-vector immunity. Other approaches to JE vaccines--including naked DNA, oral vaccination, and recombinant subunit vaccines--have been reviewed.

  9. 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

  10. 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...

  11. 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.

  12. Revisiting Recombination Signal in the Tick-Borne Encephalitis Virus: A Simulation Approach.

    PubMed

    Bertrand, Yann J K; Johansson, Magnus; Norberg, Peter

    2016-01-01

    The hypothesis of wide spread reticulate evolution in Tick-Borne Encephalitis virus (TBEV) has recently gained momentum with several publications describing past recombination events involving various TBEV clades. Despite a large body of work, no consensus has yet emerged on TBEV evolutionary dynamics. Understanding the occurrence and frequency of recombination in TBEV bears significant impact on epidemiology, evolution, and vaccination with live vaccines. In this study, we investigated the possibility of detecting recombination events in TBEV by simulating recombinations at several locations on the virus' phylogenetic tree and for different lengths of recombining fragments. We derived estimations of rates of true and false positive for the detection of past recombination events for seven recombination detection algorithms. Our analytical framework can be applied to any investigation dealing with the difficult task of distinguishing genuine recombination signal from background noise. Our results suggest that the problem of false positives associated with low detection P-values in TBEV, is more insidious than generally acknowledged. We reappraised the recombination signals present in the empirical data, and showed that reliable signals could only be obtained in a few cases when highly genetically divergent strains were involved, whereas false positives were common among genetically similar strains. We thus conclude that recombination among wild-type TBEV strains may occur, which has potential implications for vaccination with live vaccines, but that these events are surprisingly rare.

  13. Revisiting Recombination Signal in the Tick-Borne Encephalitis Virus: A Simulation Approach

    PubMed Central

    Johansson, Magnus; Norberg, Peter

    2016-01-01

    The hypothesis of wide spread reticulate evolution in Tick-Borne Encephalitis virus (TBEV) has recently gained momentum with several publications describing past recombination events involving various TBEV clades. Despite a large body of work, no consensus has yet emerged on TBEV evolutionary dynamics. Understanding the occurrence and frequency of recombination in TBEV bears significant impact on epidemiology, evolution, and vaccination with live vaccines. In this study, we investigated the possibility of detecting recombination events in TBEV by simulating recombinations at several locations on the virus’ phylogenetic tree and for different lengths of recombining fragments. We derived estimations of rates of true and false positive for the detection of past recombination events for seven recombination detection algorithms. Our analytical framework can be applied to any investigation dealing with the difficult task of distinguishing genuine recombination signal from background noise. Our results suggest that the problem of false positives associated with low detection P-values in TBEV, is more insidious than generally acknowledged. We reappraised the recombination signals present in the empirical data, and showed that reliable signals could only be obtained in a few cases when highly genetically divergent strains were involved, whereas false positives were common among genetically similar strains. We thus conclude that recombination among wild-type TBEV strains may occur, which has potential implications for vaccination with live vaccines, but that these events are surprisingly rare. PMID:27760182

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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

  16. 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

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. 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

  10. Factors affecting recombinant Western equine encephalitis virus glycoprotein production in the baculovirus system.

    PubMed

    Toth, Ann M; Geisler, Christoph; Aumiller, Jared J; Jarvis, Donald L

    2011-12-01

    In an effort to produce processed, soluble Western equine encephalitis virus (WEEV) glycoproteins for subunit therapeutic vaccine studies, we isolated twelve recombinant baculoviruses designed to express four different WEEV glycoprotein constructs under the transcriptional control of three temporally distinct baculovirus promoters. The WEEV glycoprotein constructs encoded full-length E1, the E1 ectodomain, an E26KE1 polyprotein precursor, and an artificial, secretable E2E1 chimera. The three different promoters induced gene expression during the immediate early (ie1), late (p6.9), and very late (polh) phases of baculovirus infection. Protein expression studies showed that the nature of the WEEV construct and the timing of expression both influenced the quantity and quality of recombinant glycoprotein produced. The full-length E1 product was insoluble, irrespective of the timing of expression. Each of the other three constructs yielded soluble products and, in these cases, the timing of expression was important, as higher protein processing efficiencies were generally obtained at earlier times of infection. However, immediate early expression did not yield detectable levels of every WEEV product, and expression during the late (p6.9) or very late (polh) phases of infection provided equal or higher amounts of processed, soluble product. Thus, while earlier foreign gene expression can provide higher recombinant glycoprotein processing efficiencies in the baculovirus system, in the case of the WEEV glycoproteins, earlier expression did not provide larger amounts of high quality, soluble recombinant glycoprotein product.

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. 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

  16. 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

  17. 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.

  18. 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

  19. 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.

  20. 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

  1. 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

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. Evolutionary genetics and vector adaptation of recombinant viruses of the western equine encephalitis antigenic complex provides new insights into alphavirus diversity and host switching

    PubMed Central

    Allison, Andrew B.; Stallknecht, David E.; Holmes, Edward C.

    2014-01-01

    Western equine encephalitis virus (WEEV), Highlands J virus (HJV), and Fort Morgan virus (FMV) are the sole representatives of the WEE antigenic complex of the genus Alphavirus, family Togaviridae, that are endemic to North America. All three viruses have their ancestry in a recombination event involving eastern equine encephalitis virus (EEEV) and a Sindbis (SIN)-like virus that gave rise to a chimeric alphavirus that subsequently diversified into the present-day WEEV, HJV, and FMV. Here, we present a comparative analysis of the genetic, ecological, and evolutionary relationships among these recombinant-origin viruses, including the description of a nsP4 polymerase mutation in FMV that allows it to circumvent the host range barrier to Asian tiger mosquito cells, a vector species that is normally refractory to infection. Notably, we also provide evidence that the recombination event that gave rise to these three WEEV antigenic complex viruses may have occurred in North America. PMID:25463613

  2. Evolutionary genetics and vector adaptation of recombinant viruses of the western equine encephalitis antigenic complex provides new insights into alphavirus diversity and host switching.

    PubMed

    Allison, Andrew B; Stallknecht, David E; Holmes, Edward C

    2015-01-01

    Western equine encephalitis virus (WEEV), Highlands J virus (HJV), and Fort Morgan virus (FMV) are the sole representatives of the WEE antigenic complex of the genus Alphavirus, family Togaviridae, that are endemic to North America. All three viruses have their ancestry in a recombination event involving eastern equine encephalitis virus (EEEV) and a Sindbis (SIN)-like virus that gave rise to a chimeric alphavirus that subsequently diversified into the present-day WEEV, HJV, and FMV. Here, we present a comparative analysis of the genetic, ecological, and evolutionary relationships among these recombinant-origin viruses, including the description of a nsP4 polymerase mutation in FMV that allows it to circumvent the host range barrier to Asian tiger mosquito cells, a vector species that is normally refractory to infection. Notably, we also provide evidence that the recombination event that gave rise to these three WEEV antigenic complex viruses may have occurred in North America.

  3. 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

  4. 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

  5. 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.

  6. 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.

  7. 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

  8. 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

  9. 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 ...

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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.

  13. Complete genome sequence of a new recombinant echovirus 25 strain isolated from a neonatal patient with hand, foot, and mouth disease complicated by encephalitis in Beijing, China.

    PubMed

    Li, Hongjie; Meng, Yixing; Pang, Lin; Liang, Jinqiu; Lu, Hongping; Wang, Qi; Liang, Pu; Cao, Jinfeng; Liu, Shun-Ai; Cheng, Jun

    2015-06-01

    Although human echovirus 25 (E-25), a type of the enterovirus B species, is implicated in aseptic meningitis, information on its gene structure, evolution, and virulence are limited. We report here the complete genome sequence of a novel recombinant E-25 strain (E25/2010/CHN/BJ) isolated from a neonate with hand, foot, and mouth disease complicated by encephalitis in Beijing, China in 2010. The complete viral genome consists of 7429 nucleotides (nts), including a 6585-nt open reading frame. Phylogenetic dendrogram based on VP1 gene regions revealed that this strain belonged to subgroup D4, which contains the other E-25 strains isolated from China in recent years. The difference in the amino acid sites (P130S, K/T135I) of the VP1 region may affect its immunogenicity. SimPlot and Bootscan analyses suggested that E25/2010/CHN/BJ is a recombination result of E-25 and Coxsackievirus B3 (CVB-3) strains. Our results would facilitate the study of the origin, evolution, and molecular epidemiology of E-25.

  14. Recombinant subviral particles from tick-borne encephalitis virus are fusogenic and provide a model system for studying flavivirus envelope glycoprotein functions.

    PubMed Central

    Schalich, J; Allison, S L; Stiasny, K; Mandl, C W; Kunz, C; Heinz, F X

    1996-01-01

    Recombinant subviral particles (RSPs) obtained by coexpression of the envelope (E) and premembrane (prM) proteins of tick-borne encephalitis virus in COS cells (S. L. Allison, K. Stadler, C. W. Mandl, C. Kunz, and F. X. Heinz, J. Virol. 69:5816-5820, 1995) were extensively characterized and shown to be ordered structures containing envelope glycoproteins with structural and functional properties very similar to those in the virion envelope. The particles were spherical, with a diameter of about 30 nm and a buoyant density of 1.14 g/cm3 in sucrose gradients. They contained mature E proteins with endoglycosidase H-resistant glycans as well as fully cleaved mature M proteins. Cleavage of prM, which requires an acidic pH in exocytic compartments, could be inhibited by treatment of transfected cells with ammonium chloride, implying a common maturation pathway for RSPs and virions. RSPs incorporated [14C]choline but not [3H]uridine, demonstrating that they contain lipid but probably lack nucleic acid. The envelope proteins of RSPs exhibited a native antigenic and oligomeric structure compared with virions, and incubation at an acidic pH (pH <6.5) induced identical conformational changes and structural rearrangements, including an irreversible quantitative conversion of dimers to trimers. The RSPs were also shown to be functionally active, inducing membrane fusion in a low-pH-dependent manner and demonstrating the same specific hemagglutination activity as whole virions. Tick-borne encephalitis virus RSPs thus represent an excellent model system for investigating the structural basis of viral envelope glycoprotein functions. PMID:8676481

  15. 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

  16. 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

  17. 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.

  18. 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

  19. 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

  20. Recombinant nucleocapsid-like particles from dengue-2 virus induce protective CD4+ and CD8+ cells against viral encephalitis in mice.

    PubMed

    Gil, Lázaro; López, Carlos; Lazo, Laura; Valdés, Iris; Marcos, Ernesto; Alonso, Ruby; Gambe, Ailyn; Martín, Jorge; Romero, Yaremis; Guzmán, María G; Guillén, Gerardo; Hermida, Lisset

    2009-10-01

    Virus-like particles are a highly effective type of subunit vaccine that mimics the overall structure of virus particles without containing infectious genetic material. In this work, a particulate form of the recombinant capsid protein from dengue-2 was evaluated in mice to determine the level of protection against viral challenge and to measure the antigen-induced cell-mediated immunity (CMI). The nucleocapsid-like particles (NLPs) adjuvanted with alum did not induce antiviral antibodies. However, splenocytes from the immunized animals secreted high levels of IFN-gamma upon virus stimulation, and a significant protection rate was achieved after challenge with lethal dengue-2 virus. Finally, both IFN-gamma secretion and protection against viral encephalitis were demonstrated to be dependent on CD4(+) and CD8(+) cells. This study provides new evidences regarding the protective role of the CMI in the mouse model without the induction of neutralizing antibodies. Further studies in non-human primates or humanized mice should be carried out to elucidate the usefulness of the NLPs as a potential vaccine candidate against dengue disease.

  1. 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

  2. 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

  3. 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.

  4. 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.

  5. Whole genome analysis of porcine astroviruses detected in Japanese pigs reveals genetic diversity and possible intra-genotypic recombination.

    PubMed

    Ito, Mika; Kuroda, Moegi; Masuda, Tsuneyuki; Akagami, Masataka; Haga, Kei; Tsuchiaka, Shinobu; Kishimoto, Mai; Naoi, Yuki; Sano, Kaori; Omatsu, Tsutomu; Katayama, Yukie; Oba, Mami; Aoki, Hiroshi; Ichimaru, Toru; Mukono, Itsuro; Ouchi, Yoshinao; Yamasato, Hiroshi; Shirai, Junsuke; Katayama, Kazuhiko; Mizutani, Tetsuya; Nagai, Makoto

    2017-02-09

    Porcine astroviruses (PoAstVs) are ubiquitous enteric virus of pigs that are distributed in several countries throughout the world. Since PoAstVs are detected in apparent healthy pigs, the clinical significance of infection is unknown. However, AstVs have recently been associated with a severe neurological disorder in animals, including humans, and zoonotic potential has been suggested. To date, little is known about the epidemiology of PoAstVs among the pig population in Japan. In this report, we present an analysis of nearly complete genomes of 36 PoAstVs detected by a metagenomics approach in the feces of Japanese pigs. Based on a phylogenetic analysis and pairwise sequence comparison, 10, 5, 15, and 6 sequences were classified as PoAstV2, PoAstV3, PoAstV4, and PoAstV5, respectively. Co-infection with two or three strains was found in individual fecal samples from eight pigs. The phylogenetic trees of ORF1a, ORF1b, and ORF2 of PoAstV2 and PoAstV4 showed differences in their topologies. The PoAstV3 and PoAstV5 strains shared high sequence identities within each genotype in all ORFs; however, one PoAstV3 strain and one PoAstV5 strain showed considerable sequence divergence from the other PoAstV3 and PoAstV5 strains, respectively, in ORF2. Recombination analysis using whole genomes revealed evidence of multiple possible intra-genotype recombination events in PoAstV2 and PoAstV4, suggesting that recombination might have contributed to the genetic diversity and played an important role in the evolution of Japanese PoAstVs.

  6. 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

  7. 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.

  8. 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 ...

  9. 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

  10. 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.

  11. 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.

  12. Identification of Novel Recombinant Forms of Hepatitis B Virus Generated from Genotypes Ae and G in HIV-1-Positive Japanese Men Who Have Sex with Men

    PubMed Central

    Kawahata, Takuya; Mori, Haruyo; Furubayashi, Keiichi; Taniguchi, Yasushi; Itoda, Ichiro; Komano, Jun

    2015-01-01

    Abstract The rare hepatitis B virus (HBV) genotype G (HBV/G) coinfects HIV-1-positive individuals along with HBV/A and generates recombinants. However, the circulation of HBV A/G recombinants remains poorly understood. This molecular epidemiologic study examined HBV A/G recombinants in Japanese HIV-1-positive men who have sex with men (MSM). Initially, blood specimens submitted for confirmatory tests of HIV infection in Osaka and Tokyo, Japan, from 2006 to 2013 were examined for HIV-1, and HIV-1-positive specimens were screened for HBV. Among 817 specimens from HIV-1-positive individuals, HBsAg was detected in 59 specimens; of these, HBV/Ae (alternatively A2), a subgenotype of HBV/A prevalent in Europe and North America, was identified in 70.2%, HBV/C in 17.5%, and HBV/G in 10.5%, and HBV/E in 1.8% according to the core gene sequence. The full-length genome analysis of HBV was performed on HBV/G-positive specimens because some HBV A/G recombinants were historically overlooked by genotyping based on a partial genome analysis. It revealed that five of the specimens contained novel Ae/G recombinants, the core gene of which had a high sequence similarity to HBV/G. Detailed analyses showed that novel recombinants were coinfected with HBV/Ae in a recombinant-dominant fashion. No major drug-resistant mutations were found in the newly identified HBV Ae/G recombinants. Some of the individuals asymptomatically coinfected with HIV/HBV suffered mild liver injury. This study demonstrated that novel Ae/G HBV recombinants were identified in Japanese HIV-1-positive MSM. The pathogenicity of novel HBV Ae/G recombinants should be examined in a future longitudinal study. Surveillance of such viruses in HIV-1-positive individuals should be emphasized. PMID:25825936

  13. Identification of Novel Recombinant Forms of Hepatitis B Virus Generated from Genotypes Ae and G in HIV-1-Positive Japanese Men Who Have Sex with Men.

    PubMed

    Kojima, Yoko; Kawahata, Takuya; Mori, Haruyo; Furubayashi, Keiichi; Taniguchi, Yasushi; Itoda, Ichiro; Komano, Jun

    2015-07-01

    The rare hepatitis B virus (HBV) genotype G (HBV/G) coinfects HIV-1-positive individuals along with HBV/A and generates recombinants. However, the circulation of HBV A/G recombinants remains poorly understood. This molecular epidemiologic study examined HBV A/G recombinants in Japanese HIV-1-positive men who have sex with men (MSM). Initially, blood specimens submitted for confirmatory tests of HIV infection in Osaka and Tokyo, Japan, from 2006 to 2013 were examined for HIV-1, and HIV-1-positive specimens were screened for HBV. Among 817 specimens from HIV-1-positive individuals, HBsAg was detected in 59 specimens; of these, HBV/Ae (alternatively A2), a subgenotype of HBV/A prevalent in Europe and North America, was identified in 70.2%, HBV/C in 17.5%, and HBV/G in 10.5%, and HBV/E in 1.8% according to the core gene sequence. The full-length genome analysis of HBV was performed on HBV/G-positive specimens because some HBV A/G recombinants were historically overlooked by genotyping based on a partial genome analysis. It revealed that five of the specimens contained novel Ae/G recombinants, the core gene of which had a high sequence similarity to HBV/G. Detailed analyses showed that novel recombinants were coinfected with HBV/Ae in a recombinant-dominant fashion. No major drug-resistant mutations were found in the newly identified HBV Ae/G recombinants. Some of the individuals asymptomatically coinfected with HIV/HBV suffered mild liver injury. This study demonstrated that novel Ae/G HBV recombinants were identified in Japanese HIV-1-positive MSM. The pathogenicity of novel HBV Ae/G recombinants should be examined in a future longitudinal study. Surveillance of such viruses in HIV-1-positive individuals should be emphasized.

  14. 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.

  15. 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

  16. Production and characterization of monoclonal antibodies against recombinant tethered follicle-stimulating hormone from Japanese eel Anguilla japonica.

    PubMed

    Kim, Dae-Jung; Park, Chae-Won; Kim, Dong-Wan; Park, Hong-Kyu; Byambaragchaa, Munkhzaya; Lee, Nam-Sil; Hong, Sun-Mee; Seo, Mi-Young; Kang, Myung-Hwa; Min, Kwan-Sik

    2016-07-01

    We prepared monoclonal antibodies (mAbs) against a recombinant tethered follicle-stimulating hormone (rec-FSH) from Japanese eel Anguilla japonica that was produced in Escherichia coli. Positive hybridomas (clones eFA-C5, eFA-C10, eFA-C11, eFA-C12, eFA-C13, and eFB-C14) were selected by using the eel FSH antigen in ELISA, and anti-eel FSH mAbs were purified from culture supernatants by performing affinity chromatography. Three of the 6mAbs were characterized and their isotypes were identified as IgG2b (eFA-C5 and eFA-C11) and IgG1 (eFB-C14). In western blotting assays, the mAbs recognized the antigen as a 24.3-kDa band, and further detected bands of 34 and 32kDa in the supernatants of CHO cells transfected with cDNA encoding tethered eel FSHβ/α and LHβ/α, respectively. PNase F-mediated deglycosylation of the recombinant proteins resulted in a drastic reduction in their molecular weight, to 7-9kDa. The mAbs eFA-C5 and eFA-C11 recognized the eel FSHα-subunit that is commonly encoded among glycoprotein hormones, whereas eFB-C14 recognized the eel FSHβ-subunit, and immunohistochemical analysis revealed that the staining by these mAbs was specifically localized in the eel pituitary. We also established an ELISA system for detecting rec-tethered FSHβ/α and LHβ/α produced from CHO cell lines. Measurement of biological activities in vitro revealed that only weak activity of rec-FSHβ/α was detected. The activity of rec-LHβ/α was found to be increased in a dose-dependent manner for eel oocyte maturation.

  17. Combined prime-boost vaccination against tick-borne encephalitis (TBE) using a recombinant vaccinia virus and a bacterial plasmid both expressing TBE virus non-structural NS1 protein

    PubMed Central

    Aleshin, SE; Timofeev, AV; Khoretonenko, MV; Zakharova, LG; Pashvykina, GV; Stephenson, JR; Shneider, AM; Altstein, AD

    2005-01-01

    Background Heterologous prime-boost immunization protocols using different gene expression systems have proven to be successful tools in protecting against various diseases in experimental animal models. The main reason for using this approach is to exploit the ability of expression cassettes to prime or boost the immune system in different ways during vaccination procedures. The purpose of the project was to study the ability of recombinant vaccinia virus (VV) and bacterial plasmid, both carrying the NS1 gene from tick-borne encephalitis (TBE) virus under the control of different promoters, to protect mice against lethal challenge using a heterologous prime-boost vaccination protocol. Results The heterologous prime-boost vaccination protocol, using a VV recombinant and bacterial plasmid, both containing the NS1 TBE virus protein gene under the control of different promoters, achieved a high level of protection in mice against lethal challenge with a highly pathogenic TBE virus strain. No signs of pronounced TBE infection were detected in the surviving animals. Conclusion Heterologous prime-boost vaccination protocols using recombinant VV and bacterial plasmids could be used for the development of flavivirus vaccines. PMID:16076390

  18. Protection of Mice from Fatal Measles Encephalitis by Vaccination with Vaccinia Virus Recombinants Encoding Either the Hemagglutinin or the Fusion Protein

    NASA Astrophysics Data System (ADS)

    Drillien, Robert; Spehner, Daniele; Kirn, Andre; Giraudon, Pascale; Buckland, Robin; Wild, Fabian; Lecocq, Jean-Pierre

    1988-02-01

    Vaccinia virus recombinants encoding the hemagglutinin or fusion protein of measles virus have been constructed. Infection of cell cultures with the recombinants led to the synthesis of authentic measles proteins as judged by their electrophoretic mobility, recognition by antibodies, glycosylation, proteolytic cleavage, and presentation on the cell surface. Mice vaccinated with a single dose of the recombinant encoding the hemagglutinin protein developed antibodies capable of both inhibiting hemagglutination activity and neutralizing measles virus, whereas animals vaccinated with the recombinant encoding the fusion protein developed measles neutralizing antibodies. Mice vaccinated with either of the recombinants resisted a normally lethal intracerebral inoculation of a cell-associated measles virus subacute sclerosing panencephalitis strain.

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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

  4. Expression of recombinant T-cell epitopes of major Japanese cedar pollen allergens fused with cholera toxin B subunit in Escherichia coli.

    PubMed

    Hoang, Vinh Van; Zou, Yanshuang; Kurata, Kentaro; Enomoto, Keiichi

    2015-05-01

    Peptides containing T-cell epitopes from allergens, which are not reactive to allergen-specific IgE, are appropriate candidates as antigens for specific immunotherapy against allergies. To develop a vaccine that can be used in practical application to prevent and treat Japanese cedar pollen allergy, four major T-cell epitopes from the Cry j 1 antigen and six from the Cry j 2 antigen were selected to design cry j 1 epi and cry j 2 epi, DNA constructs encoding artificial polypeptides of the selected epitopes. To apply cholera toxin B subunit (CTB) as an adjuvant, cry j 1 epi and cry j 2 epi were linked and then fused to the CTB gene in tandem to construct a fusion gene, ctb-linker-cry j 1 epi- cry j 2 epi-flag. The fusion gene was introduced into a pET-28a(+) vector and expressed in Escherichia coli BL21(DE3). The expressed recombinant protein was purified by a His-tag affinity column and confirmed by western blot analysis using anti-CTB and anti-FLAG antibodies. The purified recombinant protein also proved to be antigenic against anti-Cry j 1 and anti-Cry j 2 antibodies. Expression of the recombinant protein induced with 1mM IPTG reached a maximum in 3-5h, and recovery of the affinity-purified recombinant protein was approximately 120mg/L of culture medium. The present study indicates that production of sufficient amounts of recombinant protein with antigenic epitopes may be possible by recombinant techniques using E. coli or other bacterial strains for protein expression.

  5. 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

  6. 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

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. 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

  12. 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.

  13. 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

  14. Infection and transmission of live recombinant Newcastle disease virus vaccines in Rock Pigeons, European House Sparrows, and Japanese Quail

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In China and Mexico, engineered recombinant Newcastle disease virus (rNDV) strains are used as live vaccines for the control of Newcastle disease and as vectors to express the avian influenza virus hemagglutinin (HA) gene to control avian influenza in poultry. In this study, non-target species wer...

  15. Evaluation of the infection and transmission of wild type and recombinant strains of Newcastle disease virus in Japanese Quail

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Newcastle disease virus (NDV) causes a range of clinical disease ranging from asymptomatic infection to severe disease with high mortality. Vaccination for NDV is practiced almost worldwide in commercial chickens. Attenuated live vaccines are most commonly used, with recombinant vaccines becoming ...

  16. 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 ...

  17. 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 ...

  18. 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

  19. 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.

  20. Effects of recombinant eel growth hormone on the uptake of ( sup 35 S)sulfate by ceratobranchial cartilages of the Japanese eel, Anguilla japonica

    SciTech Connect

    Duan, C.M.; Inui, Y. )

    1990-08-01

    Effects of growth hormone (GH) on the synthesis of mucopolysaccharide by ceratobranchial cartilages of the Japanese eel, Anguilla japonica, were examined by monitoring the in vitro uptake of ({sup 35}S)sulfate. The ({sup 35}S)sulfate uptake decreased rapidly to one-third of the initial level during the first 3 days after hypophysectomy, and decreased gradually thereafter. When hypophysectomized eels were injected intramuscularly with recombinant eel GH (2 micrograms/g), the plasma GH concentrations increased maximally after 6 hr, and declined rapidly thereafter. On the other hand, the sulfate uptake increased significantly after 12 hr, and high levels were maintained until 48 hr. The stimulating effect of GH was dose dependent (0.02-2 micrograms/g). However, the addition of eel GH (0.05-5 micrograms/ml) to the culture medium did not affect the sulfate uptake by hypophysectomized eel cartilages, suggesting that the stimulative action of GH on the sulfate uptake by the cartilages is indirect.

  1. 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

  2. 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.

  3. [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.

  4. 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

  5. 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

  6. [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.

  7. 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.

  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. 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)

  10. 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).

  11. Prevalence estimation of tick-borne encephalitis virus (TBEV) antibodies in dogs from Finland using novel dog anti-TBEV IgG MAb-capture and IgG immunofluorescence assays based on recombinant TBEV subviral particles.

    PubMed

    Levanov, Lev; Vera, Cristina Pérez; Vapalahti, Olli

    2016-07-01

    Tick-borne encephalitis (TBE) is one of the most dangerous human neurological infections occurring in Europe and Northern parts of Asia with thousands of cases and millions vaccinated against it. The risk of TBE might be assessed through analyses of the samples taken from wildlife or from animals which are in close contact with humans. Dogs have been shown to be a good sentinel species for these studies. Serological assays for diagnosis of TBE in dogs are mainly based on purified and inactivated TBEV antigens. Here we describe novel dog anti-TBEV IgG monoclonal antibody (MAb)-capture assay which is based on TBEV prME subviral particles expressed in mammalian cells from Semliki Forest virus (SFV) replicon as well as IgG immunofluorescence assay (IFA) which is based on Vero E6 cells transfected with the same SFV replicon. We further demonstrate their use in a small-scale TBEV seroprevalence study of dogs representing different regions of Finland. Altogether, 148 dog serum samples were tested by novel assays and results were compared to those obtained with a commercial IgG enzyme immunoassay (EIA), hemagglutination inhibition test and IgG IFA with TBEV infected cells. Compared to reference tests, the sensitivities of the developed assays were 90-100% and the specificities of the two assays were 100%. Analysis of the dog serum samples showed a seroprevalence of 40% on Åland Islands and 6% on Southwestern archipelago of Finland. In conclusion, a specific and sensitive EIA and IFA for the detection of IgG antibodies in canine sera were developed. Based on these assays the seroprevalence of IgG antibodies in dogs from different regions of Finland was assessed and was shown to parallel the known human disease burden as the Southwestern archipelago and Åland Islands in particular had considerable dog TBEV antibody prevalence and represent areas with high risk of TBE for humans.

  12. Production of hepatitis E virus-like particles presenting multiple foreign epitopes by co-infection of recombinant baculoviruses

    PubMed Central

    Shima, Ryoichi; Li, Tian Cheng; Sendai, Yutaka; Kataoka, Chikako; Mori, Yoshio; Abe, Takayuki; Takeda, Naokazu; Okamoto, Toru; Matsuura, Yoshiharu

    2016-01-01

    Hepatitis E virus (HEV) causes not only endemics via a fecal-oral route but also sporadic cases via zoonotic transmission or blood transfusion. HEV-like particles (HEV-LP) produced by using a baculovirus expression system are considered a candidate for mucosal vaccines for HEV infection. In this study, we attempted to produce a chimeric HEV-LP presenting various foreign epitopes on its surface. Expression of the recombinant capsid proteins carrying a myc- or FLAG-tag inserted between amino acid residues 488 and 489, which are located in the exterior loop on the protruding domain of the HEV capsid, resulted in the production of recombinant HEV-LP. Although expression of the recombinant capsid protein carrying the HA-tag inserted at the same site failed to produce any particles, co-expression with the myc-tagged capsid protein successfully yielded a chimeric HEV-LP consisting of both recombinant capsid proteins. Immunoprecipitation analyses confirmed that the chimeric particles present these foreign epitopes on the surface. Similar results were obtained for the expression of the recombinant capsid proteins carrying neutralizing epitopes of Japanese encephalitis virus. These results suggest the chimeric HEV-LP system provides a novel vaccine carrier that can accommodate multiple neutralizing epitopes on its surface. PMID:26905478

  13. 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.

  14. 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)

  15. 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

  16. 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

  17. Anti-NMDA-receptor encephalitis: a severe, multistage, treatable disorder presenting with psychosis.

    PubMed

    Wandinger, Klaus-Peter; Saschenbrecker, Sandra; Stoecker, Winfried; Dalmau, Josep

    2011-02-01

    Anti-NMDA-receptor encephalitis is a severe, treatable and potentially reversible disorder presenting with memory deficits, psychiatric symptoms and seizures. Initially described in young patients with ovarian teratoma, the disease is meanwhile increasingly recognized also in women without tumours, in men and in children. The presence of anti-glutamate receptor (type NMDA) autoantibodies in serum or cerebrospinal fluid is specific for this novel and widely underdiagnosed disorder. Early recognition is crucial since prognosis largely depends on adequate immunotherapy and, in paraneoplastic cases, complete tumour removal. Indirect immunofluorescence using NMDA-type glutamate receptors recombinantly expressed in human cells is a highly competent method for diagnosing anti-NMDA-receptor encephalitis.

  18. Japanese Encephalitis Vaccine: What You Need to Know

    MedlinePlus

    ... is spread through the bite of an infected mosquito. It does not spread from person to person. • ... best way to prevent JE is to avoid mosquito bites. Your doctor can advise you. 3 Sthoismveapcecoinpele ...

  19. Japanese Encephalitis Virus Immunoglobulin M Antibodies in Porcine Sera

    DTIC Science & Technology

    1985-10-01

    were washed 3 times with 0.0514 Tween - 80 in phosphate- Results buffered saline solution (PBSS). , Test sample-The test sample serum (50 1±l), diluted to...specimens were not pretreated. Plates were again washed 3 times (within 2 to 3 days after viremia) had strong JEV IgM with miss- Tween 80 . reactivity...The plates were then washed Density-gradient fractionation-Preinfection, immedi- 5 times with Pss- Tween 80 . Label-A 1:500 dilution of horseradish

  20. Basic biotechnologies essential for the Japanese chemical industry in the 1990's and beyond. Bioreactors, large-scale mammalian cell culture, recombinant DNAs, functional protein systems, and bio-electronic devices

    SciTech Connect

    Fujimura, R.K.

    1992-01-01

    The purpose of the program is to induce private company laboratories to do research considered essential for the development of new technologies. One group of projects initially funded under the program was in the field of biotechnology. More specifically, the biotechnology projects were aimed at developing technologies for the chemical industry for the decade of the 1990's. Various projects dealt with bioreactors, large-scale cell culture, and recombinant DNA. These initial biotechnology projects have now been completed. The report reviews their accomplishments and assesses their possible impact on the Japanese chemical industry. A new project on functional protein complexes was added in 1989. Progress on the nine-year project is also reviewed. Finally, an assessment is provided of the biotechnology components of an unrelated group of projects being administered by the Research and Development Association for Future Electron Devices. The relevant components in the program involve bio-electronic devices and functional protein complexes. The objectives are to mimic biological systems for use in microsensors, information transmission and processing, artificial tissues and organs, robotics, and artificial intelligence.

  1. [Autoimmune encephalitis as a cause of psychosis].

    PubMed

    Suokas, Kimmo; Kampman, Olli

    2014-01-01

    Antibodies directed to the surface structures of nerve cells may cause autoimmune encephalitis. It may cause limbic encephalitis requiring intensive care, or symptoms are restricted to psychosis. This disease may be impossible to distinguish clinically from a functional psychotic illness. Some of the cases are paraneoplastic, i.e. associated with a diagnosed or latent malignant neoplasia, most commonly ovarian teratoma. The first line treatment for autoimmune encephalitis is an immunomodulatory combination therapy with immunoglobulin and methylprednisolone. We recommend screening of the most common NMDAR and VGKC antibodies related to autoimmune encephalitis from patients having developed a new psychosis.

  2. [Anti-NMDA-receptor encephalitis].

    PubMed

    Engen, Kristine; Agartz, Ingrid

    2016-06-01

    BACKGROUND In 2007 a clinical disease caused by autoantibodies directed against the N-methyl-D-aspartate (NMDA) receptor was described for the first time. Anti-NMDA-receptor encephalitis is a subacute, autoimmune neurological disorder with psychiatric manifestations. The disease is a form of limbic encephalitis and is often paraneoplastic. The condition is also treatable. In this review article we examine the development of the disease, clinical practice, diagnostics and treatment.MATERIAL AND METHOD The article is based on references retrieved from searches in PubMed, and a discretionary selection of articles from the authors' own literature archive.RESULTS The disease most frequently affects young women. It may initially be perceived as a psychiatric condition, as it usually presents in the form of delusions, hallucinations or mania. The diagnosis should be suspected in patients who later develop neurological symptoms such as various movement disorders, epileptic seizures and autonomic instability. Examination of serum or cerebrospinal fluid for NMDA receptor antibodies should be included in the assessment of patients with suspected encephalitis. MRI, EEG and assessment for tumours are important tools in diagnosing the condition and any underlying malignancy.INTERPRETATION If treatment is initiated early, the prognosis is good. Altogether 75 % of patients will fully recover or experience significant improvement. Apart from surgical resection of a possible tumour, the treatment consists of immunotherapy. Because of good possibilities for treatment, it is important that clinicians, particularly those in acute psychiatry, are aware of and alert to this condition.

  3. Anti-NMDA encephalitis: an uncommon, autoimmune mediated form of encephalitis.

    PubMed

    Azizyan, Avetis; Albrektson, Joshua R; Maya, Marcel M; Pressman, Barry D; Moser, Franklin

    2014-08-01

    We report an interesting case of a 19 year old female with findings on MRI suggestive of viral encephalitis. An extensive workup was negative for infectious causes and she was subsequently diagnosed with anti-NMDA encephalitis. Anti-NMDA encephalitis is a highly lethal but treatable form of autoimmune encephalitis that has recently been characterized. It is frequently found in young women and associated with an underlying teratoma. Although rare, this diagnosis should be considered in young females for whom a rapid onset of encephalitis cannot be explained by more common causes.

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

    PubMed Central

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

    2016-01-01

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

  5. Surveillance for Western equine encephalitis St. Louis encephalitis and West Nile viruses using reverse transcription loop-mediated isothermal amplification

    SciTech Connect

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

    2016-01-25

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

  6. Surveillance for Western equine encephalitis St. Louis encephalitis and West Nile viruses using reverse transcription loop-mediated isothermal amplification

    DOE PAGES

    Meagher, Robert J.; Ball, Cameron Scott; Langevin, Stanley A.; ...

    2016-01-25

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

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

    PubMed

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

    2016-01-01

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

  8. Eastern Equine Encephalitis Treated With Intravenous Immunoglobulins

    PubMed Central

    Mukerji, Shibani S.; Lam, Alice D.

    2016-01-01

    We report the case of a 68-year-old man from southeastern Massachusetts presenting with encephalitis due to eastern equine encephalitis (EEE) virus. Despite the high morbidity and mortality rate of EEE, the patient made a near complete recovery in the setting of receiving early intravenous immunoglobulins. PMID:26740855

  9. Eastern Equine Encephalitis Treated With Intravenous Immunoglobulins.

    PubMed

    Mukerji, Shibani S; Lam, Alice D; Wilson, Michael R

    2016-01-01

    We report the case of a 68-year-old man from southeastern Massachusetts presenting with encephalitis due to eastern equine encephalitis (EEE) virus. Despite the high morbidity and mortality rate of EEE, the patient made a near complete recovery in the setting of receiving early intravenous immunoglobulins.

  10. Production and characterization of monoclonal antibody specific to recombinant dengue multi-epitope protein.

    PubMed

    Abhyankar, Ajay Vinayak; Bhargava, Rakesh; Jana, Asha Mukul; Sahni, Ajay Kumar; Rao, P V Lakshmana

    2008-06-01

    Monoclonal antibodies against novel dengue recombinant protein were produced following immunization of Balb/c mice with recombinant dengue multi-epitope protein (r-DMEP) expressed in Escherichia coli vector and purified in a single-step chromatography system. Antigenicity of r-DMEP was evaluated by dot enzyme immunoassay. Mice were immunized intraperitoneally with five doses each of 100 microg of this novel antigen at 1-week intervals and a final intravenous booster dose prior to the fusion. Hybridomas resulted from fusion of myeloma cells and splenocytes using PEG-1500 as an additive. Selection of the hybrids was done using HAT medium, and the hybrids thus selected were finally screened qualitatively and quantitatively by dot and plate immunoassays, respectively. Five antibody secretory hybrid clones exhibited specific reactivity against r-DMEP by dot-ELISA, whereas a lone clone was found to be cross-reactive with Japanese encephalitis virus (JEV). Monoclonal antibodies (MAbs) specific to r-DME protein recognized the envelope and non-structural epitopes by Western blot analysis. These MAbs were further checked for their diagnostic efficacy using dengue suspected clinical samples and found overall sensitivity and specificity for DRDE dipstick ELISA. MAb-based dipstick ELISA results were 85%, 75% and 85%, 90%, respectively.

  11. Viral encephalitis: current treatments and future perspectives.

    PubMed

    Domingues, Renan Barros

    2012-12-01

    Several viruses may cause central nervous system infections that lead to a broad range of clinical manifestations. The course of the viral encephalitis can be acute, sub acute, or chronic. Some viruses have the ability to enter into the brain and cause direct injury, while others activate inflammatory cells that attack the central nervous system (CNS) secondarily. Some types of viral encephalitis occur in previously healthy individuals, while others affect immunocompromised patients. The epidemiology of viral encephalitis has undergone changes in recent years. Factors such as evolving lifestyles and ecological changes have had a considerable impact on the epidemiology of some types of viral encephalitis. The result is a change in the etiology spectrum of viral encephalitis, with new types of encephalitis arising or returning from time to time. Many scientific achievements in neuroimaging, molecular diagnosis, antiviral therapy, immunomodulatory treatments, and neurointensive care have allowed more precise and earlier diagnoses and more efficient treatments, resulting in improved outcomes. Despite these advances, there is still considerable morbidity and mortality related to these disorders. This aim of this article is to review the current knowledge of the current drugs used in the management of the most important viral encephalitis, focusing on the mechanisms of action, efficacy, and side effects of the drugs. In addition, future perspectives in this area will be addressed. Despite the technological advances, much effort has yet to be undertaken to reduce the impact of these potentially devastating diseases.

  12. Case Definitions, Diagnostic Algorithms, and Priorities in Encephalitis: Consensus Statement of the International Encephalitis Consortium

    PubMed Central

    Venkatesan, A.; Tunkel, A. R.; Bloch, K. C.; Lauring, A. S.; Sejvar, J.; Bitnun, A.; Stahl, J-P.; Mailles, A.; Drebot, M.; Rupprecht, C. E.; Yoder, J.; Cope, J. R.; Wilson, M. R.; Whitley, R. J.; Sullivan, J.; Granerod, J.; Jones, C.; Eastwood, K.; Ward, K. N.; Durrheim, D. N.; Solbrig, M. V.; Guo-Dong, L.; Glaser, C. A.; Sheriff, Heather; Brown, David; Farnon, Eileen; Messenger, Sharon; Paterson, Beverley; Soldatos, Ariane; Roy, Sharon; Visvesvara, Govinda; Beach, Michael; Nasci, Roger; Pertowski, Carol; Schmid, Scott; Rascoe, Lisa; Montgomery, Joel; Tong, Suxiang; Breiman, Robert; Franka, Richard; Keuhnert, Matt; Angulo, Fred; Cherry, James

    2013-01-01

    Background.Encephalitis continues to result in substantial morbidity and mortality worldwide. Advances in diagnosis and management have been limited, in part, by a lack of consensus on case definitions, standardized diagnostic approaches, and priorities for research. Methods.In March 2012, the International Encephalitis Consortium, a committee begun in 2010 with members worldwide, held a meeting in Atlanta to discuss recent advances in encephalitis and to set priorities for future study. Results.We present a consensus document that proposes a standardized case definition and diagnostic guidelines for evaluation of adults and children with suspected encephalitis. In addition, areas of research priority, including host genetics and selected emerging infections, are discussed. Conclusions.We anticipate that this document, representing a synthesis of our discussions and supported by literature, will serve as a practical aid to clinicians evaluating patients with suspected encephalitis and will identify key areas and approaches to advance our knowledge of encephalitis. PMID:23861361

  13. Virus meningo-encephalitis in Slovenia

    PubMed Central

    Vesenjak-Zmijanac, J.; Bedjanič, M.; Rus, S.; Kmet, J.

    1955-01-01

    An organism was isolated from the blood of a patient clinically diagnosed as suffering from virus meningo-encephalitis; the organism causes illness and death in white mice. The antigen prepared from the brains of mice infected with this organism fixes complement with sera from typical cases of virus meningo-encephalitis. From its biological and serological characteristics, the isolated organism appears to belong to the group of neurotropic viruses and to be the causative agent of virus meningo-encephalitis in Slovenia. PMID:14378996

  14. CD4+ T cells provide protection against acute lethal encephalitis caused by Venezuelan equine encephalitis virus.

    PubMed

    Yun, Nadezhda E; Peng, Bi-Hung; Bertke, Andrea S; Borisevich, Viktoriya; Smith, Jennifer K; Smith, Jeanon N; Poussard, Allison L; Salazar, Milagros; Judy, Barbara M; Zacks, Michele A; Estes, D Mark; Paessler, Slobodan

    2009-06-19

    Studying the mechanisms of host survival resulting from viral encephalitis is critical to the development of vaccines. Here we have shown in several independent studies that high dose treatment with neutralizing antibody prior to intranasal infection with Venezuelan equine encephalitis virus had an antiviral effect in the visceral organs and prolonged survival time of infected mice, even in the absence of alphabeta T cells. Nevertheless, antibody treatment did not prevent the development of lethal encephalitis. On the contrary, the adoptive transfer of primed CD4(+) T cells was necessary to prevent lethal encephalitis in mice lacking alphabeta T cell receptor.

  15. Psychiatric aspects of herpes simplex encephalitis, tick-borne encephalitis and herpes zoster encephalitis among immunocompetent patients.

    PubMed

    Więdłocha, Magdalena; Marcinowicz, Piotr; Stańczykiewicz, Bartłomiej

    2015-01-01

    The psychopathological symptoms occurring in the course of diseases associated with infections are often initially isolated and non-characteristic, and may cause diagnostic difficulties. Moreover, such disorders tend to be less responsive to psychiatric management. Among possible causes such as trauma, neoplasm and vascular changes, inflammatory changes of the brain as a result of a viral infection should also be considered. There were 452 registered cases of viral encephalitis in Poland in 2010, and although not very prevalent they remain a severe and life-threatening condition. What is more, the frequently occurring neurological and psychiatric complications of viral encephalitis often result in permanent disabilities, causing a significant decrease in the quality of life. This article presents the three types of encephalitis that are most prevalent among immunocompetent patients in Poland, i.e. herpes simplex encephalitis (HSE), tick-borne encephalitis (TBE) and herpes zoster encephalitis (HZE). The psychopathology of the acute phase of the infection, the residual symptoms, features apparent in imaging studies and some neuropathological aspects are also presented. The paper also focuses on psychiatric aspects of the diagnostics and treatment of the described conditions. The clinical pictures of these infections are quite specific, although they cover a wide range of symptoms, and these characteristic features are described. The aim of this review is also to show the significance of thorough diagnostics and a multidisciplinary approach to patients with viral CNS infections.

  16. Anti-NMDA Receptor Encephalitis During Pregnancy

    PubMed Central

    Mathis, Stéphane; Pin, Jean-Christophe; Pierre, Fabrice; Ciron, Jonathan; Iljicsov, Anna; Lamy, Matthias; Neau, Jean-Philippe

    2015-01-01

    Abstract Anti-N-methyl-D-aspartate receptor (anti-MMDAR) encephalitis is an immune-mediated encephalitis mainly affecting young women. We describe the case of a 21-year-old woman who developed a classical form of anti-NMDAR encephalitis during the 10th week of gestation. The patient had been treated with methylpredinsolone and intravenous immunoglobulins. Birth history of the child was normal, with normal APGAR score. The clinical symptoms of the patient have improved after a few months. This rare occurrence during pregnancy (only 9 other cases described) presents an opportunity to highlight the importance of making the earliest possible diagnosis of this treatable and potentially reversible encephalitis, and to educate gynecologists, psychiatrists, anesthetists, and neurologists on this potential cause of psychiatric and neurological manifestations during pregnancy. PMID:26131809

  17. Emergency Neurologic Life Support: Meningitis and Encephalitis.

    PubMed

    Gaieski, David F; Nathan, Barnett R; O'Brien, Nicole F

    2015-12-01

    Bacterial meningitis and viral encephalitis, particularly herpes simplex encephalitis, are severe neurological infections that, if not treated promptly and effectively, lead to poor neurological outcome or death. Because treatment is more effective if given early, the topic of meningitis and encephalitis was chosen as an Emergency Neurological Life Support protocol. This protocol provides a practical approach to recognition and urgent treatment of bacterial meningitis and encephalitis. Appropriate imaging, spinal fluid analysis, and early empiric treatment is discussed. Though uncommon in its full form, the typical clinical triad of headache, fever, and neck stiffness should alert the clinical practitioner to the possibility of a central nervous system infection. Early attention to the airway and maintaining normotension is crucial in treatment of these patients, as is rapid treatment with anti-infectives and, in some cases, corticosteroids.

  18. The Laboratory Diagnosis of Autoimmune Encephalitis

    PubMed Central

    Lee, Sang Kun; Lee, Soon-Tae

    2016-01-01

    Autoimmune encephalitis is a group of encephalitis syndromes that cause altered mentality, memory decline, or seizures in association with the presence of serum and cerebrospinal fluid (CSF) autoantibodies (auto-Abs). An early diagnosis enables early treatments. The detection of auto-Abs is a confirmatory diagnosis. Tissue-based assay, cell-based immunoassay, and immunoblotting are used to detect various autoantibodies. The CSF test for the presence of antibodies is important because it is more sensitive and reflects disease activity in many autoimmune encephalitis, although antibody tests can be negative even in the presence of autoimmune encephalitis. EEG is often abnormal, but nonspecific. A unilateral or bilateral medial temporal T2 high signal is a common finding in MRI. Fludeoxyglucose-positron emission tomography is sometimes useful for diagnosis in patients with normal MRI. PMID:28101474

  19. Cysticercal encephalitis with cortical blindness.

    PubMed

    Prasad, Rajniti; Thakur, Neha; Mohanty, C; Singh, M K; Mishra, O P; Singh, Utpal Kant

    2010-10-21

    The authors report a 6-year-old boy, who had presented with low-grade fever, altered sensorium, headache and seizure for 5 days. On examination, he had features of raised intracranial pressure with left VI cranial-nerve palsy and bilateral extensor plantar response. CT scan showed multiple calcifications in cerebral cortex. MRI cranium showed multiple cysts involving whole of the brain. He was diagnosed as having cysticercal encephalitis, based on immunological and imaging study. He was managed with 20% mannitol, phenytoin and albendazole, and regained consciousness 7 days later, but had residual neurological deficit as left-lower-limb monoparesis and visual acuity of just projection of rays (PR+) and perception of light (PL+).

  20. [Saint Louis encephalitis: case report].

    PubMed

    Carballo, Carolina; Cabana, Magdalena; Ledezma, Francisca; Pascual, Carolina; Cazes, Claudia; Mistchenko, Alicia; López, Eduardo

    2016-08-01

    Saint Louis encephalitis is transmitted by Culex mosquitoes. In Argentina sporadic cases are registered. Symptomatic illness is unusual in children. We present a case of meningoencephalitis caused by an uncommon viral infection. The clinical signs and symptoms are unusual for pediatric patients and the bilateral thalamic compromise showed on magnetic resonance has not been described previously. An 8-year-old girl consulted due to fever, behavior disorders and ataxia. Clonus and neck stiffness were detected at physical exam. Cerebrospinal fluid revealed mononuclear leukocytosis; bilateral ischemic compromise was observed in thalamus by magnetic resonance. Saint Louis virus was confirmed by serology: serum and cerebrospinal fluid IgM were positive during the acute phase of the disease and serum IgG was positive four weeks later. Most of the signs and symptoms of the disease were resolved, however mild behavior disorders were observed as acute sequelae up to 45 days after hospital discharge.

  1. Encephalitis

    MedlinePlus

    ... are transmitted by mosquitoes or other blood-sucking insects. Mosquito-borne viruses can cause infections that include ... Ganciclovir (Cytovene) Foscarnet (Foscavir) Some viruses, such as insect-borne viruses, don't respond to these treatments. ...

  2. Encephalitis

    MedlinePlus

    ... Viruses and other germs that are transmitted by insects, like West Nile virus (transmitted through a mosquito ... are only transmitted through the bite of infected insects; it's not possible to catch them from other ...

  3. Encephalitis

    MedlinePlus

    ... a mosquito bite) and the germs that cause Lyme disease and Rocky Mountain spotted fever (transmitted through tick ... West Nile Virus Meningitis Rocky Mountain Spotted Fever Lyme Disease Contact Us Print Resources Send to a friend ...

  4. Encephalitis and AMPA receptor antibodies

    PubMed Central

    Höftberger, Romana; van Sonderen, Agnes; Leypoldt, Frank; Houghton, David; Geschwind, Michael; Gelfand, Jeffrey; Paredes, Mercedes; Sabater, Lidia; Saiz, Albert; Titulaer, Maarten J.; Graus, Francesc

    2015-01-01

    Objective: We report the clinical features, comorbidities, and outcome of 22 newly identified patients with antibodies to the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR). Methods: This was a retrospective review of patients diagnosed between May 2009 and March 2014. Immunologic techniques have been reported previously. Results: Patients' median age was 62 years (range 23–81; 14 female). Four syndromes were identified: 12 (55%) patients presented with distinctive limbic encephalitis (LE), 8 (36%) with limbic dysfunction along with multifocal/diffuse encephalopathy, one with LE preceded by motor deficits, and one with psychosis with bipolar features. Fourteen patients (64%) had a tumor demonstrated pathologically (5 lung, 4 thymoma, 2 breast, 2 ovarian teratoma) or radiologically (1 lung). Additional antibodies occurred in 7 patients (3 onconeuronal, 1 tumor-related, 2 cell surface, and 1 tumor-related and cell surface), all with neurologic symptoms or tumor reflecting the concurrent autoimmunity. Treatment and outcome were available from 21 patients (median follow-up 72 weeks, range 5–266): 5 had good response to immunotherapy and tumor therapy, 10 partial response, and 6 did not improve. Eventually 5 patients died; all had a tumor or additional paraneoplastic symptoms related to onconeuronal antibodies. Coexistence of onconeuronal antibodies predicted a poor outcome (p = 0.009). Conclusion: Anti-AMPAR encephalitis usually manifests as LE, can present with other symptoms or psychosis, and is paraneoplastic in 64% of cases. Complete and impressive neurologic improvement can occur, but most patients have partial recovery. Screening for a tumor and onconeuronal antibodies is important because their detection influences outcome. PMID:25979696

  5. Herpes encephalitis preceded by ipsilateral vestibular neuronitis.

    PubMed

    Philpot, Stephen J; Archer, John S

    2005-11-01

    A 74-year-old woman developed vertigo and jerk nystagmus to the left with normal cerebral imaging. Three days later she developed fever, altered mental state and left medial temporal lobe hypodensity, confirmed on lumbar puncture to be due to herpes simplex type 1 encephalitis. We propose that the patient had vestibular neuronitis caused by HSV-1 that progressed to ipsilateral temporal lobe encephalitis.

  6. Japanese Characters in Written Japanese.

    ERIC Educational Resources Information Center

    Buck, James H.

    From the sixth to the eighth century A.D., Japan was the recipient of massive cultural infusions from China. This acceptance of the Chinese pattern included, and to a great extent was based on, the acceptance of the Chinese language. The Chinese writing system was applied to Japanese because there was no other model to follow and in spite of the…

  7. Relevance of Neuroinflammation and Encephalitis in Autism

    PubMed Central

    Kern, Janet K.; Geier, David A.; Sykes, Lisa K.; Geier, Mark R.

    2016-01-01

    In recent years, many studies indicate that children with an autism spectrum disorder (ASD) diagnosis have brain pathology suggestive of ongoing neuroinflammation or encephalitis in different regions of their brains. Evidence of neuroinflammation or encephalitis in ASD includes: microglial and astrocytic activation, a unique and elevated proinflammatory profile of cytokines, and aberrant expression of nuclear factor kappa-light-chain-enhancer of activated B cells. A conservative estimate based on the research suggests that at least 69% of individuals with an ASD diagnosis have microglial activation or neuroinflammation. Encephalitis, which is defined as inflammation of the brain, is medical diagnosis code G04.90 in the International Classification of Disease, 10th revision; however, children with an ASD diagnosis are not generally assessed for a possible medical diagnosis of encephalitis. This is unfortunate because if a child with ASD has neuroinflammation, then treating the underlying brain inflammation could lead to improved outcomes. The purpose of this review of the literature is to examine the evidence of neuroinflammation/encephalitis in those with an ASD diagnosis and to address how a medical diagnosis of encephalitis, when appropriate, could benefit these children by driving more immediate and targeted treatments. PMID:26834565

  8. Anti-NMDA Receptor Encephalitis in a Pregnant Woman.

    PubMed

    Kim, Jiyoung; Park, Seung Ha; Jung, Yu Ri; Park, Soon Won; Jung, Dae Soo

    2015-06-01

    Anti N-methyl-D-aspartate (NMDA) receptor encephalitis is one of the most common types of autoimmune synaptic encephalitis. Anti-NMDA receptor encephalitis commonly occurs in young women with ovarian teratoma. It has variable clinical manifestations and treatment responses. Sometimes it is misdiagnosed as a psychiatric disorder or viral encephalitis. To the best of our knowledge, anti-NMDA receptor encephalitis is a rare condition in pregnant women. We report a case of anti-NMDA receptor encephalitis in a pregnant woman who presented with abnormal behavior, epileptic seizure, and hypoventilation.

  9. Pediatric Herpes Simplex Virus Encephalitis Complicated by N-Methyl-D-aspartate Receptor Antibody Encephalitis.

    PubMed

    Bamford, Alasdair; Crowe, Belinda H A; Hacohen, Yael; Lin, Jean-Pierre; Clarke, Antonia; Tudor-Williams, Gareth; Sancho-Shimizu, Vanessa; Vincent, Angela; Lim, Ming; Pullaperuma, Sunil P

    2015-06-01

    N-methyl-D-aspartate receptor antibodies (NMDAR-Abs) can contribute to neurological relapse after herpes simplex virus encephalitis (HSE). We describe a child with NMDAR-Ab encephalitis after HSE, which was recognized and treated early. We discuss the case in the context of existing reports, and we propose a modified immunotherapy strategy to minimize risk of viral reactivation.

  10. Encephalization of Australian and New Guinean marsupials.

    PubMed

    Ashwell, K W S

    2008-01-01

    Encephalization of Australian marsupials was analyzed using the endocranial volume (ECV) of 52 species of Dasyuromorphia and Notoryctemorphia, 14 species of Peramelemorphia and 116 species of Diprotodontia from Australia and New Guinea and compared with 16 species of Ameridelphian marsupials and 3 species of native and recently introduced Australian eutherian carnivores (dingo, feral cat and feral fox). Linear regression analysis of the relationship between ECV and body weight for marsupials revealed that allometric parameters for these groups are different from those previously derived for samples of (mainly eutherian) mammals, with higher slopes for Dasyuromorphia and Diprotodontia and lower slopes for Ameridelphians and Peramelemorphia. Absolute ECV for small Australian and New Guinea marsupial carnivores (Antechinus and Sminthopsis) were found to be comparable to eutherians of similar body weight, but large marsupial carnivores such as the Tasmanian devil and thylacine had substantially smaller ECVs than eutherian carnivores of similar body weight. Similarly, members of some superfamilies within Diprotodontia (Burramyoidea, Petauroidea, Tarsipedoidea) had ECVs comparable to prosimians, whereas bandicoots, bilbies and many macropods were found to be poorly encephalized. When both encephalization quotient (EQ) and residuals from regression analysis were used to compare relative ECV of extinct/threatened species with common species there were no significant differences for any of the orders of Australian marsupials, suggesting that encephalization is not a major factor in the current extinction crisis for Australian marsupials. Similarly there were no consistent differences in relative ECV between marsupials from New Guinea and associated islands compared to Australia or between arid and non-arid Australian regions for any of the marsupial orders. The results indicate that marsupials are not uniformly poorly encephalized and that small marsupial carnivores and

  11. Molecular identification of Saint Louis encephalitis virus genotype IV in Colombia

    PubMed Central

    Hoyos-López, Richard; Soto, Sandra Uribe; Rúa-Uribe, Guillermo; Gallego-Gómez, Juan Carlos

    2015-01-01

    Saint Louis encephalitis virus (SLEV) is a member of the Japanese-encephalitis virus serocomplex of the genus Flavivirus. SLEV is broadly distributed in the Americas and the Caribbean Islands, where it is usually transmitted by mosquitoes of the genus Culex and primarily to birds and mammalian-hosts. Humans are occasionally infected by the virus and are dead-end hosts. SLEV causes encephalitis in temperate regions, while in tropical regions of the Americas, several human cases and a wide biological diversity of SLEV-strains have been reported. The phylogenetic analysis of the envelope (E) protein genes indicated eight-genotypes of SLEV with geographic overlap. The present paper describes the genotyping of two SLEV viruses detected in mosquito-pools collected in northern Colombia (department of Cordoba). We used reverse transcription-polymerase chain reaction to amplify a fragment of theE-gene to confirm the virus identity and completeE-gene sequencing for phylogenetic analysis and genotyping of the two-SLEV viruses found circulating in Córdoba. This is the first report of SLEV genotype IV in Colombia (Córdoba) in mosquitoes from a region of human inhabitation, implicating the risk of human disease due to SLEV infection. Physicians should consider SLEV as a possible aetiology for undiagnosed febrile and neurologic syndromes among their patients who report exposure to mosquito-bites. PMID:26313538

  12. Molecular identification of Saint Louis encephalitis virus genotype IV in Colombia.

    PubMed

    Hoyos-López, Richard; Soto, Sandra Uribe; Rúa-Uribe, Guillermo; Gallego-Gómez, Juan Carlos

    2015-09-01

    Saint Louis encephalitis virus (SLEV) is a member of the Japanese-encephalitis virus serocomplex of the genus Flavivirus. SLEV is broadly distributed in the Americas and the Caribbean Islands, where it is usually transmitted by mosquitoes of the genus Culex and primarily to birds and mammalian-hosts. Humans are occasionally infected by the virus and are dead-end hosts. SLEV causes encephalitis in temperate regions, while in tropical regions of the Americas, several human cases and a wide biological diversity of SLEV-strains have been reported. The phylogenetic analysis of the envelope (E) protein genes indicated eight-genotypes of SLEV with geographic overlap. The present paper describes the genotyping of two SLEV viruses detected in mosquito-pools collected in northern Colombia (department of Cordoba). We used reverse transcription-polymerase chain reaction to amplify a fragment of the E-gene to confirm the virus identity and complete E-gene sequencing for phylogenetic analysis and genotyping of the two-SLEV viruses found circulating in Córdoba. This is the first report of SLEV genotype IV in Colombia (Córdoba) in mosquitoes from a region of human inhabitation, implicating the risk of human disease due to SLEV infection. Physicians should consider SLEV as a possible aetiology for undiagnosed febrile and neurologic syndromes among their patients who report exposure to mosquito-bites.

  13. PSYCHOTIC DISORDERS GENERATED BY AUTOIMMUNE ENCEPHALITIS (CLINICAL CASE).

    PubMed

    Craciun, Georgiana; Cucoş, Liliana; Ungureanu, Elena; Pendefunda, L; Petrariu, F D; Nechita, Petronela

    2015-01-01

    Encephalitis is a brain inflammation, which could involve also the meninges. The etiology of encephalitis could be: viral, bacterial, fungal or autoimmune. Anti-NMDAR encephalitis is an immune disorder, easy to diagnose and is a treatable condition. Most patients with anti-NMDAR encephalitis develop a multistage illness that progresses from psychosis, memory deficits, seizures, to catatonic state and breathing instability. We present a case report of a 20-year old woman, who presented: amnesia, visual hallucination, illusions, seizures after that occurred following autoimmune encephalitis. The exact incidence of anti-NMDAR encephalitis is unknown, but it seems to be more frequent than any other known paraneoplastic encephalitis. The present case is important considering that autoimmune encephalitis is a rare frequency disorder in Romania, with patients presenting resounding psychiatric and neurological manifestations.

  14. Susceptibility of Peruvian Mosquitoes to Eastern Equine Encephalitis virus

    DTIC Science & Technology

    2008-07-01

    VECTOR/PATHOGEN/HOST INTERACTION, TRANSMISSION Susceptibility of Peruvian Mosquitoes to Eastern Equine Encephalitis Virus M. J. TURELL,1 M. L...the Amazon Basin, near Iquitos, Peru, and used in experimental studies to evaluate their susceptibility to strains of eastern equine encephalitis virus...enzootic vector of EEEV in this region. KEY WORDS Peru, eastern equine encephalitis virus, transmission, mosquito Eastern equine encephalitis virus (EEEV

  15. Encephalitis and GABAB receptor antibodies

    PubMed Central

    Höftberger, Romana; Titulaer, Maarten J.; Sabater, Lidia; Dome, Balazs; Rózsás, Anita; Hegedus, Balazs; Hoda, Mir Alireza; Laszlo, Viktoria; Ankersmit, Hendrik Jan; Harms, Lutz; Boyero, Sabas; de Felipe, Alicia; Saiz, Albert; Dalmau, Josep

    2013-01-01

    Objective: To report the clinical features of 20 newly diagnosed patients with GABAB receptor (GABABR) antibodies and determine the frequency of associated tumors and concurrent neuronal autoantibodies. Methods: Clinical data were retrospectively obtained and evaluated. Serum and CSF samples were examined for additional antibodies using methods previously reported. Results: Seventeen patients presented with seizures, memory loss, and confusion, compatible with limbic encephalitis (LE), one patient presented with ataxia, one patient presented with status epilepticus, and one patient presented with opsoclonus-myoclonus syndrome (OMS). Nineteen (95%) patients eventually developed LE during the course of the disease. Small-cell lung cancer (SCLC) was identified in 10 (50%) patients, all with LE. Treatment and outcome was available from 19 patients: 15 showed complete (n = 7) or partial (n = 8) neurologic improvement after steroids, IV immunoglobulins, or plasma exchange and oncologic treatment when indicated; 1 patient died of tumor progression shortly after the first cycle of immunotherapy, and 3 were not treated. Five patients with SCLC had additional onconeuronal antibodies (Ri, amphiphysin, or SOX1), and 2 without tumor had GAD65 and NMDAR antibodies, respectively. GABABR antibodies were not detected in serum of 116 patients with SCLC without neurologic symptoms. Conclusion: Our study confirms GABABR as an autoantigen of paraneoplastic and nonparaneoplastic LE and expands the phenotype of GABABR antibodies to ataxia, OMS, and status epilepticus. The long-term prognosis is dictated by the presence of a tumor. Recognition of syndromes associated with GABABR antibodies is important because they usually respond to treatment. PMID:24068784

  16. The Diagnosis and Treatment of Autoimmune Encephalitis

    PubMed Central

    2016-01-01

    Autoimmune encephalitis causes subacute deficits of memory and cognition, often followed by suppressed level of consciousness or coma. A careful history and examination may show early clues to particular autoimmune causes, such as neuromyotonia, hyperekplexia, psychosis, dystonia, or the presence of particular tumors. Ancillary testing with MRI and EEG may be helpful for excluding other causes, managing seizures, and, rarely, for identifying characteristic findings. Appropriate autoantibody testing can confirm specific diagnoses, although this is often done in parallel with exclusion of infectious and other causes. Autoimmune encephalitis may be divided into several groups of diseases: those with pathogenic antibodies to cell surface proteins, those with antibodies to intracellular synaptic proteins, T-cell diseases associated with antibodies to intracellular antigens, and those associated with other autoimmune disorders. Many forms of autoimmune encephalitis are paraneoplastic, and each of these conveys a distinct risk profile for various tumors. Tumor screening and, if necessary, treatment is essential to proper management. Most forms of autoimmune encephalitis respond to immune therapies, although powerful immune suppression for weeks or months may be needed in difficult cases. Autoimmune encephalitis may relapse, so follow-up care is important. PMID:26754777

  17. Dietary quality and encephalization in platyrrhine primates

    PubMed Central

    Allen, Kari L.; Kay, Richard F.

    2012-01-01

    The high energetic costs of building and maintaining large brains are thought to constrain encephalization. The ‘expensive-tissue hypothesis’ (ETH) proposes that primates (especially humans) overcame this constraint through reduction of another metabolically expensive tissue, the gastrointestinal tract. Small guts characterize animals specializing on easily digestible diets. Thus, the hypothesis may be tested via the relationship between brain size and diet quality. Platyrrhine primates present an interesting test case, as they are more variably encephalized than other extant primate clades (excluding Hominoidea). We find a high degree of phylogenetic signal in the data for diet quality, endocranial volume and body size. Controlling for phylogenetic effects, we find no significant correlation between relative diet quality and relative endocranial volume. Thus, diet quality fails to account for differences in platyrrhine encephalization. One taxon, in particular, Brachyteles, violates predictions made by ETH in having a large brain and low-quality diet. Dietary reconstructions of stem platyrrhines further indicate that a relatively high-quality diet was probably in place prior to increases in encephalization. Therefore, it is unlikely that a shift in diet quality was a primary constraint release for encephalization in platyrrhines and, by extrapolation, humans. PMID:21831898

  18. Structure and Expression of Genes for Flavivirus Immunogens

    DTIC Science & Technology

    1988-02-01

    cDNAs. Keywords: Japanese encephalitis virus; Dengue virus; Flaviviruses; Subunit vaccines; Diagnosis; Mice; Gene mapping; Biotechnology; BW; CDNA; Cloning; Dengue fever ; DNA probes; Recombinant DNA.

  19. A Practical Approach to Meningitis and Encephalitis.

    PubMed

    Richie, Megan B; Josephson, S Andrew

    2015-12-01

    Meningitis is an inflammatory syndrome involving the meninges that classically manifests with headache and nuchal rigidity and is diagnosed by cerebrospinal fluid examination. In contrast, encephalitis refers to inflammation of the brain parenchyma itself and often results in focal neurologic deficits or seizures. In this article, the authors review the differential diagnosis of meningitis and encephalitis, with an emphasis on infectious etiologies. The recommended practical clinical approach focuses on early high-yield diagnostic testing and empiric antimicrobial administration, given the high morbidity associated with these diseases and the time-sensitive nature of treatment initiation. If the initial workup does not yield a diagnosis, further etiology-specific testing based upon risk factors and clinical characteristics should be pursued. Effective treatment is available for many causes of meningitis and encephalitis, and when possible should address both the primary disease process as well as potential complications.

  20. Tick-borne encephalitis in the USSR*

    PubMed Central

    Graščenkov, N. I.

    1964-01-01

    The author gives the history of the study of tick-borne encephalitis in the USSR, following it up with a description of the etiological and epidemiological aspects and of the pathology, symptomology, diagnosis, treatment, and prevention of the disease. He stresses that other ticks as well as the main vectors of the virus, Ixodes, transmit the disease, in particular Dermacentor and Haemaphysalis. A detailed account of tick-borne encephalitis in the USSR may be of value in the study of the rather similar forms of the disease now being encountered more and more frequently in countries of South-East Asia as well as of northern and eastern Europe. PMID:14153408

  1. Tick-borne encephalitis in children.

    PubMed

    Rostasy, Kevin

    2012-06-01

    This review is a summary of the most important clinical findings and implications of tick-borne encephalitis (TBE) in children. It is based on a Pubmed search with the terms "tick-borne encephalitis", "children", "infection", "meningitis", "meningoencephalitis", and "outcome". TBE in children shares several features with their adult counterpart but has overall a better prognosis. Nevertheless, TBE is associated with substantial morbidity and mortality in a small group of children and seems to cause cognitive dysfunctions, which needs to be studied in further detail.

  2. Herpes simplex encephalitis: some interesting presentations.

    PubMed

    Jha, S; Jose, M; Kumar, V

    2003-09-01

    Herpes Simplex Encephalitis (HSE) is the most common cause of fatal viral encephalitis. A high index of suspicion is mandatory for early diagnosis and successful therapy to restrict morbidity and mortality. We report 4 patients of HSE, with interesting presentations, viz. brainstem involvement in an immunosuppressed patient, Kluver-Bucy Syndrome-a consequence of untreated HSE, HSE in the postpartum period mistaken as cortical venous thrombosis, and response to inadequate treatment. They demonstrate the wide spectrum of clinical features, pitfalls in diagnosis, and a variable response to therapy in HSE.

  3. Novel variant of tickborne encephalitis virus, Russia.

    PubMed

    Ternovoi, Vladimir A; Protopopova, Elena V; Chausov, Eugene V; Novikov, Dmitry V; Leonova, Galina N; Netesov, Sergey V; Loktev, Valery B

    2007-10-01

    We isolated a novel strain of tickborne encephalitis virus (TBEV), Glubinnoe/2004, from a patient with a fatal case in Russia. We sequenced the strain, whose landmark features included 57 amino acid substitutions and 5 modified cleavage sites. Phylogenetically, Glubinnoe/2004 is a novel variant that belongs to the Eastern type of TBEV.

  4. Anorexia nervosa with herpes simplex encephalitis

    PubMed Central

    George, G. C. W.

    1981-01-01

    Studies of patients suffering from anorexia nervosa appear to show an increased immunity to certain infections, as well as immunological deficiencies. This is the report of a patient with anorexia nervosa who developed herpes simplex encephalitis, a condition associated with lowered immunological defence mechanisms. PMID:7301681

  5. Migrating Birds and Tickborne Encephalitis Virus

    PubMed Central

    Lundkvist, Åke; Falk, Kerstin I.; Garpmo, Ulf; Bergström, Sven; Lindegren, Gunnel; Sjöstedt, Anders; Mejlon, Hans; Fransson, Thord; Haemig, Paul D.; Olsen, Björn

    2007-01-01

    During spring and autumn 2001, we screened 13,260 migrating birds at Ottenby Bird Observatory, Sweden, and found 3.4% were infested with ticks. Four birds, each a different passerine species, carried tickborne encephalitis virus (TBEV)–infected ticks (Ixodes ricinus). Migrating birds may play a role in the geographic dispersal of TBEV-infected ticks. PMID:17953095

  6. Paraneoplastic limbic encephalitis: clinico-pathological correlations.

    PubMed Central

    Bakheit, A M; Kennedy, P G; Behan, P O

    1990-01-01

    Three new cases of limbic encephalitis in association with malignancy are reported. The literature on this condition is reviewed and the clinical, laboratory and histopathological features of cases proven at necropsy are correlated. The possible pathogenic mechanism of this disorder is discussed. PMID:1963440

  7. Can Herpes Simplex Virus Encephalitis Cause Aphasia?

    ERIC Educational Resources Information Center

    Naude, H.; Pretorius, E.

    2003-01-01

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

  8. The Japanese Mind: Understanding Contemporary Japanese Culture.

    ERIC Educational Resources Information Center

    Davies, Roger J., Ed.; Ikeno, Osamu, Ed.

    This collection of essays offers an overview of contemporary Japanese culture, and can serve as a resource for classes studying Japan. The 28 essays offer an informative, accessible look at the values, attitudes, behavior patterns, and communication styles of modern Japan from the unique perspective of the Japanese people. Filled with examples…

  9. Bullying in Japanese Schools.

    ERIC Educational Resources Information Center

    Kobayashi, Futoshi

    Noting that although many Western educators praise the Japanese educational system because of its students' academic achievements, schools in Japan have developed severe and prevalent problems with student bullying. This paper examines the problem of bullying in Japanese schools. Part 1 of the paper reviews bullying incidents in Japanese schools…

  10. Sarcocystis neurona encephalitis in a dog.

    PubMed

    Cooley, A J; Barr, B; Rejmanek, D

    2007-11-01

    A 1.5-year-old male Feist dog was presented to a veterinarian for reluctance to stand on the hind legs. Treatment included dexamethasone and resulted in a favorable initial response, but posterior paresis returned and progressed to recumbency, hyperesthesia, and attempts to bite the owner. The dog was euthanized. The brain was negative for rabies by fluorescent antibody analysis. Multiple foci of encephalitis were found in the cerebrum and particularly in the cerebellum. Protozoa morphologically consistent with Sarcocystis sp. were identified at sites of intense inflammation and malacia. Additionally, multiple schizonts were identified in areas without inflammation. Immunohistochemistry using both polyclonal and monoclonal antibodies specific for Sarcocystis neurona was strongly positive. No reaction to polyclonal antisera for Toxoplasma gondii or Neospora caninum was found. Polymerase chain reaction confirmed that the protozoa were S. neurona. Additional aberrant hosts for S. neurona other than horses have been identified, but S. neurona encephalitis has not been documented previously in the dog.

  11. Acute encephalitis as initial presentation of primary HIV infection.

    PubMed

    Nzwalo, Hipólito; Añón, Rosário Pazos; Àguas, Maria João

    2012-07-03

    Acute encephalitis is a life-threatening condition. A wide variety of infectious agents are implicated and in many patients no cause is found. HIV acute seroconversion illness can rarely present as acute encephalitis. Although most experts agree in starting antiretroviral treatment in severe acute HIV infection, the evidence of the benefits are still lacking. The authors report a case of severe acute encephalitis as a primary presentation of HIV infection in which introduction of highly active antiretroviral treatment resulted in clinical recovery. This case highlights the need to consider HIV infection in the differential diagnosis of treatable viral encephalitis.

  12. Frequent rhabdomyolysis in anti-NMDA receptor encephalitis.

    PubMed

    Lim, Jung-Ah; Lee, Soon-Tae; Kim, Tae-Joon; Moon, Jangsup; Sunwoo, Jun-Sang; Byun, Jung-Ick; Jung, Keun-Hwa; Jung, Ki-Young; Chu, Kon; Lee, Sang Kun

    2016-09-15

    The aim of this study was to analyze the clinical presentation and provocation factors of rhabdomyolysis in anti-NMDAR encephalitis. Among the 16 patients with anti-NMDAR encephalitis in our institutional cohort, nine patients had elevated CK enzyme levels and clinical evidence of rhabdomyolysis. Rhabdomyolysis was more frequent after immunotherapy. The use of dopamine receptor blocker (DRB) increased the risk of rhabdomyolysis. None of the patients without rhabdomyolysis received DRBs. Rhabdomyolysis is a frequent complication in anti-NMDAR encephalitis and more common after immunotherapy and the use of DRBs increases the risk. Therefore, DRBs should be administered carefully in patients with anti-NMDAR encephalitis.

  13. Multiple Paths to Encephalization and Technical Civilizations

    NASA Astrophysics Data System (ADS)

    Schwartzman, David; Middendorf, George

    2011-12-01

    We propose consideration of at least two possible evolutionary paths for the emergence of intelligent life with the potential for technical civilization. The first is the path via encephalization of homeothermic animals; the second is the path to swarm intelligence of so-called superorganisms, in particular the social insects. The path to each appears to be facilitated by environmental change: homeothermic animals by decreased climatic temperature and for swarm intelligence by increased oxygen levels.

  14. Sarcocystis calchasi encephalitis in a rock pigeon.

    PubMed

    Ushio, Nanako; Watanabe, Ken-ichi; Chambers, James K; Shibato, Tokuhiro; Nakayama, Hiroyuki; Uchida, Kazuyuki

    2015-11-01

    A rock pigeon (Columba livia) caught in Akihabara, Tokyo, showed neurological symptoms, such as head tilt and circling. Pathological examinations revealed abundant Sarcocystic cysts in the skeletal muscle and myocardium with mild myositis, and numerous schizonts and sarcocysts with severe multifocal granulomatous T-lymphocytic infiltration in the central nervous system. A Sarcocystis calchasi-specific gene was detected in the muscle and brain. This case indicates S. calchasi was distributed in Japan and caused severe encephalitis to rock pigeons.

  15. Autoimmune encephalitis in psychiatric institutions: current perspectives

    PubMed Central

    Bost, Chloe; Pascual, Olivier; Honnorat, Jérôme

    2016-01-01

    Autoimmune encephalitis is a rare and newly described group of diseases involving autoantibodies directed against synaptic and neuronal cell surface antigens. It comprises a wide range of neuropsychiatric symptoms. Sensitive and specific diagnostic tests such as cell-based assay are primordial for the detection of neuronal cell surface antibodies in patients’ cerebrospinal fluid or serum and determine the treatment and follow-up of the patients. As neurological symptoms are fairly well described in the literature, this review focuses on the nature of psychiatric symptoms occurring at the onset or during the course of the diseases. In order to help the diagnosis, the main neurological symptoms of the most representative synaptic and neuronal cell surface autoantibodies were detailed. Finally, the exploration of these autoantibodies for almost a decade allowed us to present an overview of autoimmune encephalitis incidence in psychiatric disease and the general guidelines for the management of psychiatric manifestations. For the majority of autoimmune encephalitis, the prognosis depends on the rapidity of the detection, identification, and the management of the disease. Because the presence of pronounced psychiatric symptoms drives patients to psychiatric institutions and can hinder the diagnosis, the aim of this work is to provide clues to help earlier detection by physicians and thus provide better medical care to patients. PMID:27822050

  16. 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.

  17. Viral aetiology and clinico-epidemiological features of acute encephalitis syndrome in eastern India.

    PubMed

    Rathore, S K; Dwibedi, B; Kar, S K; Dixit, S; Sabat, J; Panda, M

    2014-12-01

    This study reports clinico-epidemiological features and viral agents causing acute encephalitis syndrome (AES) in the eastern Indian region through hospital-based case enrolment during April 2011 to July 2012. Blood and CSF samples of 526 AES cases were investigated by serology and/or PCR. Viral aetiology was identified in 91 (17·2%) cases. Herpes simplex virus (HSV; types I or II) was most common (16·1%), followed by measles (2·6%), Japanese encephalitis virus (1·5%), dengue virus (0·57%), varicella zoster virus (0·38%) and enteroviruses (0·19%). Rash, paresis and cranial nerve palsies were significantly higher (P < 0·05) with viral AES. Case-fatality rates were 10·9% and 6·2% in AES cases with and without viral aetiology, respectively. Simultaneous infection of HSV I and measles was observed in seven cases. This report provides the first evidence on viral aetiology of AES viruses from eastern India showing dominance of HSV that will be useful in informing the public health system.

  18. Tick-borne encephalitis: What travelers should know when visiting an endemic country

    PubMed Central

    Chrdle, Aleš; Chmelík, Václav; Růžek, Daniel

    2016-01-01

    ABSTRACT Tick-borne encephalitis (TBE) is an acute febrile illness with neurological manifestations that is prevalent in forested areas of moderate climate in Europe and Asia. TBE virus is transmitted by ticks and rarely by unpasteurized milk and dairy products. The disease burden is attributed mainly to resulting long-term disability, especially in individuals over 50 y of age. Currently, there is no causative treatment, but a very effective vaccination is available with a good safety profile. The vaccination requires 3 basic doses to be fully effective and regular boosters afterwards. An accelerated vaccination schedule enables a patient to reach reasonably protective titres within 3 to 4 weeks from the first injection. The risk of travel-related TBE is estimated to be less than the risk of acquiring typhoid fever while visiting highly endemic regions in South Asia, but more than the risk of acquiring Japanese encephalitis, meningococcal invasive disease, or rabies. The pre-travel risk assessment of acquiring TBE should consider known risk factors which include 1) the country and regions to be visited; 2) April to November season; 3) altitude less than 1500 m above the sea level; 4) duration of stay; 5) the extent of tick-exposure associated activities including leisure and professional outdoor activities within the endemic area; and 6) age and comorbidities of the traveler. A major challenge, however, is the very low awareness of the risk of contracting TBE in those who travel to industrialized European countries. PMID:27715427

  19. Genetic Recombination

    ERIC Educational Resources Information Center

    Whitehouse, H. L. K.

    1973-01-01

    Discusses the mechanisms of genetic recombination with particular emphasis on the study of the fungus Sordaria brevicollis. The study of recombination is facilitated by the use of mutants of this fungus in which the color of the ascospores is affected. (JR)

  20. Encephalitis-Associated Human Metapneumovirus Pneumonia in Adult, Australia.

    PubMed

    Fok, Anthony; Mateevici, Cristina; Lin, Belinda; Chandra, Ronil V; Chong, Victor H T

    2015-11-01

    Human metapneumovirus pneumonia, most commonly found in children, was diagnosed in an adult with encephalitis. This case suggests that testing for human metapneumovirus RNA in nasopharyngeal aspirate and cerebrospinal fluid samples should be considered in adults with encephalitis who have a preceding respiratory infection.

  1. Cardiac sympathetic dysfunction in anti-NMDA receptor encephalitis.

    PubMed

    Byun, Jung-Ick; Lee, Soon-Tae; Moon, Jangsup; Jung, Keun-Hwa; Shin, Jung-Won; Sunwoo, Jun-Sang; Lim, Jung-Ah; Shin, Yong-Won; Kim, Tae-Joon; Lee, Keon-Joo; Park, Kyung-Il; Jung, Ki-Young; Lee, Sang Kun; Chu, Kon

    2015-12-01

    Patients with anti-NMDA receptor (anti-NMDAR) encephalitis frequently suffer from autonomic dysfunctions, which can cause substantial morbidity. This study assessed cardiac autonomic functions in patients with anti-NMDAR encephalitis using heart rate variability (HRV) analysis. This was a retrospective single-center case-control study. Eleven patients with anti-NMDAR encephalitis and 15 age- and sex-matched controls were included in this study. To ensure that autonomic dysfunction does not occur in any encephalitis, we additionally analyzed HRV of 9 patients with herpes encephalitis (HSE) and compared with that of NMDAR encephalitis patients and controls. Five minute resting stationary electrocardiogram was collected from each subject, and HRV was analyzed. Total power and low frequency (LF) power were lower in anti-NMDAR encephalitis patients than those in controls (p=0.005, 0.001 respectively), indicating cardiac autonomic dysfunction especially in sympathetic system. Patients with HSE showed no significant difference in HRV parameters compared with that of controls. Cardiac autonomic dysfunction was associated with 3 month functional outcome in anti-NMDAR encephalitis patients.

  2. Genotype III Saint Louis Encephalitis Virus Outbreak, Argentina, 2005

    PubMed Central

    Ré, Viviana; Almirón, Walter R.; Farías, Adrián; Vázquez, Ana; Sanchez-Seco, María Paz; Aguilar, Javier; Spinsanti, Lorena; Konigheim, Brenda; Visintin, Andrés; García, Jorge; Morales, Maria Alejandra; Tenorio, Antonio; Contigiani, Marta

    2006-01-01

    Twenty-six years after it was last detected, Saint Louis encephalitis virus (SLEV) genotype III reemerged in 2005 in Córdoba, Argentina, where it caused an outbreak. Two genotype III SLEV strains were isolated from Culex quinquefasciatus. A 71.43% prevalence for neutralizing antibodies was found in domestic fowl in the homestead of a patient with encephalitis. PMID:17283629

  3. A case of late herpes simplex encephalitis relapse.

    PubMed

    Rigamonti, Andrea; Lauria, Giuseppe; Mantero, Vittorio; Salmaggi, Andrea

    2013-09-01

    Late relapse of herpes simplex encephalitis, defined as recurrence more than 3 months after the first initial encephalitic episode, is a rare condition. We describe the case of an adult patient who presented a relapse of herpes simplex encephalitis 8 years after the first episode occurred at the age of 57 years and review the literature of this topic.

  4. Hyperleukocytosis in a premature infant with intrauterine herpes simplex encephalitis.

    PubMed

    Underwood, M A; Wartell, A E; Borghese, R A

    2012-06-01

    Herpes encephalitis is a rare but devastating infection in premature infants. We report a 29 week gestation infant with severe intrauterine cutaneous and central nervous system herpes accompanied by hyperleukocytosis. Leukemoid reactions are not uncommon in this population, but the association of herpes encephalitis and a leukemoid reaction or hyperleukocytosis has not been reported previously.

  5. A clinical approach to diagnosis of autoimmune encephalitis.

    PubMed

    Graus, Francesc; Titulaer, Maarten J; Balu, Ramani; Benseler, Susanne; Bien, Christian G; Cellucci, Tania; Cortese, Irene; Dale, Russell C; Gelfand, Jeffrey M; Geschwind, Michael; Glaser, Carol A; Honnorat, Jerome; Höftberger, Romana; Iizuka, Takahiro; Irani, Sarosh R; Lancaster, Eric; Leypoldt, Frank; Prüss, Harald; Rae-Grant, Alexander; Reindl, Markus; Rosenfeld, Myrna R; Rostásy, Kevin; Saiz, Albert; Venkatesan, Arun; Vincent, Angela; Wandinger, Klaus-Peter; Waters, Patrick; Dalmau, Josep

    2016-04-01

    Encephalitis is a severe inflammatory disorder of the brain with many possible causes and a complex differential diagnosis. Advances in autoimmune encephalitis research in the past 10 years have led to the identification of new syndromes and biomarkers that have transformed the diagnostic approach to these disorders. However, existing criteria for autoimmune encephalitis are too reliant on antibody testing and response to immunotherapy, which might delay the diagnosis. We reviewed the literature and gathered the experience of a team of experts with the aims of developing a practical, syndrome-based diagnostic approach to autoimmune encephalitis and providing guidelines to navigate through the differential diagnosis. Because autoantibody test results and response to therapy are not available at disease onset, we based the initial diagnostic approach on neurological assessment and conventional tests that are accessible to most clinicians. Through logical differential diagnosis, levels of evidence for autoimmune encephalitis (possible, probable, or definite) are achieved, which can lead to prompt immunotherapy.

  6. A clinical approach to diagnosis of autoimmune encephalitis

    PubMed Central

    Graus, Francesc; Titulaer, Maarten J; Balu, Ramani; Benseler, Susanne; Bien, Christian G; Cellucci, Tania; Cortese, Irene; Dale, Russell C; Gelfand, Jeffrey M; Geschwind, Michael; Glaser, Carol A; Honnorat, Jerome; Höftberger, Romana; Iizuka, Takahiro; Irani, Sarosh R; Lancaster, Eric; Leypoldt, Frank; Prüss, Harald; Rae-Grant, Alexander; Reindl, Markus; Rosenfeld, Myrna R; Rostásy, Kevin; Saiz, Albert; Venkatesan, Arun; Vincent, Angela; Wandinger, Klaus-Peter; Waters, Patrick; Dalmau, Josep

    2016-01-01

    Encephalitis is a severe inflammatory disorder of the brain with many possible causes and a complex differential diagnosis. Advances in autoimmune encephalitis research in the past 10 years have led to the identification of new syndromes and biomarkers that have transformed the diagnostic approach to these disorders. However, existing criteria for autoimmune encephalitis are too reliant on antibody testing and response to immunotherapy, which might delay the diagnosis. We reviewed the literature and gathered the experience of a team of experts with the aims of developing a practical, syndrome-based diagnostic approach to autoimmune encephalitis and providing guidelines to navigate through the differential diagnosis. Because autoantibody test results and response to therapy are not available at disease onset, we based the initial diagnostic approach on neurological assessment and conventional tests that are accessible to most clinicians. Through logical differential diagnosis, levels of evidence for autoimmune encephalitis (possible, probable, or definite) are achieved, which can lead to prompt immunotherapy. PMID:26906964

  7. Encephalitis Surveillance through the Emerging Infections Program, 1997–2010

    PubMed Central

    Glaser, Carol A.

    2015-01-01

    Encephalitis is a devastating illness that commonly causes neurologic disability and has a case fatality rate >5% in the United States. An etiologic agent is identified in <50% of cases, making diagnosis challenging. The Centers for Disease Control and Prevention Emerging Infections Program (EIP) Encephalitis Project established syndromic surveillance for encephalitis in New York, California, and Tennessee, with the primary goal of increased identification of causative agents and secondary goals of improvements in treatment and outcome. The project represents the largest cohort of patients with encephalitis studied to date and has influenced case definition and diagnostic evaluation of this condition. Results of this project have provided insight into well-established causal pathogens and identified newer causes of infectious and autoimmune encephalitis. The recognition of a possible relationship between enterovirus D68 and acute flaccid paralysis with myelitis underscores the need for ongoing vigilance for emerging causes of neurologic disease. PMID:26295485

  8. Anti-NMDAR encephalitis misdiagnosed as Hashimoto's encephalopathy.

    PubMed

    Mirabelli-Badenier, M; Biancheri, R; Morana, G; Fornarino, S; Siri, L; Celle, M E; Veneselli, E; Vincent, A; Gaggero, R; Mancardi, M M

    2014-01-01

    Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a well-defined autoimmune disorder. Hashimoto's encephalopathy (HE) is a still controversial entity, lacking definite diagnostic criteria. We described a 14-year-old-girl presenting with a clinical picture consistent with the diagnosis of anti-NMDAR encephalitis, confirmed by NMDAR antibody testing. Four years earlier, she had presented a similar episode of acute encephalopathy diagnosed as HE. Anti-NMDAR encephalitis and HE share similar clinical features so that the differential diagnosis can be difficult if specific antibodies are not tested. The correct diagnosis of anti-NMDAR encephalitis is crucial to plan the appropriate management and follow-up, namely in term of oncological screening, since it can be paraneoplastic in origin. We suggest to re-evaluate the clinical history of all subjects with previous HE diagnosis in order to evaluate the possible diagnosis of anti-NMDAR encephalitis and plan the appropriate management of these patients.

  9. Insights into pediatric herpes simplex encephalitis from a cohort of 21 children from the California Encephalitis Project, 1998-2011.

    PubMed

    To, Tu M; Soldatos, Ariane; Sheriff, Heather; Schmid, D Scott; Espinosa, Natasha; Cosentino, Giorgio; Preas, Christopher P; Glaser, Carol A

    2014-12-01

    Twenty-one children with confirmed herpes simplex encephalitis were identified in the California Encephalitis Project.Noteworthy features included 6 (29%) patients with an initial negative herpes simplex virus cerebrospinal fluid polymerase chain reaction test and 13 (62%) patients with extratemporal lobe involvement identified by neuroimaging [corrected]. Eleven cases were <4 years of age, but all 4 fatal cases occurred in adolescents.

  10. ANTIGENIC VARIANTS OF EASTERN EQUINE ENCEPHALITIS VIRUS

    PubMed Central

    Casals, Jordi

    1964-01-01

    A study by hemagglutination-inhibition test showed that 19 strains of eastern equine encephalitis virus grouped themselves in two main types, which have been designated North American and South American. The former consists of ten strains from the eastern half of the United States, from Massachusetts to Florida; Jamaica, the Dominican Republic, and, subject to confirmation, Thailand. The South American type comprises nine strains from Panama, Trinidad, British Guiana, Brazil, and Argentina. The strains were isolated from different natural hosts over a period of 30 years. PMID:14151098

  11. Neuronal Surface Antibody-Mediated Autoimmune Encephalitis

    PubMed Central

    Linnoila, Jenny J.; Rosenfeld, Myrna R.; Dalmau, Josep

    2016-01-01

    In the past few years, many autoimmune encephalitides have been identified, with specific clinical syndromes and associated antibodies against neuronal surface antigens. There is compelling evidence that many of these antibodies are pathogenic and most of these encephalitides are highly responsive to immunotherapies. The clinical spectra of some of these antibody-mediated syndromes, especially those reported in only a few patients, are evolving. Others, such as anti-N-methyl-D-aspartate (NMDA) receptor encephalitis, are well characterized. Diagnosis involves recognizing the specific syndromes and identifying the antibody in a patient’s cerebrospinal fluid (CSF) and/or serum. These syndromes are associated with variable abnormalities in CSF, magnetic resonance imaging, and electroencephalography. Treatment is often multidisciplinary and should be focused upon neutralizing the effects of antibodies and eliminating their source. Overlapping disorders have been noted, with some patients having more than one neurologic autoimmune disease. In other patients, viral infections such as herpes simplex virus encephalitis trigger robust antineuronal autoimmune responses. PMID:25369441

  12. Autoimmune Schizophrenia? Psychiatric Manifestations of Hashimoto's Encephalitis

    PubMed Central

    Alam, Maryam; Adetutu, Ebun; Thakur, Richa; Gottlich, Caleb; DeBacker, Danielle L; Marks, Lianne

    2016-01-01

    Hashimoto’s encephalitis (HE), also known as steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT), can be a debilitating manifestation of an autoimmune reaction against the thyroid that is often under-diagnosed primarily due to a lack of definitive diagnostic criteria. This is a case of a 52-year-old woman who has been diagnosed with HE after presenting with recurrent and severe psychosis in conjunction with paranoia and a thyroidopathy. Her symptoms are chronic, having first been documented as presenting 15 years prior and showing progressive exacerbation in both frequency and severity. The patient’s paranoia often manifested as delusions involving family members or close friends and consequently introduced an opportunity for harm to herself and others. She showed great conviction with self-diagnoses that were proven incorrect, resulting in occasional non-compliance. Between episodes, the patient did not show evidence of symptoms. This patient struggled with several incorrect diagnoses and treatments for several years before the correct diagnosis of HE was made and displayed extreme improvement upon corticosteroid administration. This case illustrates the importance of increasing awareness of HE as well as including HE in a differential diagnosis when any patient presents with psychosis and concurrent thyroidopathy. Hashimoto’s encephalitis follows putative characteristics of autoimmune diseases, exhibiting a higher incidence in women as compared to men, presenting with increased titers of autoantibodies, and showing dramatic amelioration when treated with corticosteroids. PMID:27672526

  13. Balint's syndrome in subacute HIV encephalitis.

    PubMed Central

    Schnider, A; Landis, T; Regard, M

    1991-01-01

    A 45 year old patient with AIDS is described in whom Balint's syndrome developed over several days without other higher cognitive defects. Radiological findings were typical of subacute HIV encephalitis involving mainly the white matter of the occipital lobes with extension into the parietal and temporal lobe on the left side and into the temporal lobe on the right side. While the patient could usually recognise only one single component within her visual field, her performance in reading much improved if she was allowed to observe the examiner writing. This finding is attributed to well preserved movement perception in our patient, which may have helped her in directing her visual attention. The preservation of movement perception despite damage to the lateral temporo-occipital area may be due to the distinct pathology of subacute HIV encephalitis, which leaves the cortex and adjacent subcortical white matter virtually intact and therefore allows information transfer between primary visual areas in the occipital lobe and movement specific areas in the lateral temporo-occipital area through U-fibres. Images PMID:1955902

  14. Autoimmune Schizophrenia? Psychiatric Manifestations of Hashimoto's Encephalitis.

    PubMed

    Haider, Ali S; Alam, Maryam; Adetutu, Ebun; Thakur, Richa; Gottlich, Caleb; DeBacker, Danielle L; Marks, Lianne

    2016-07-05

    Hashimoto's encephalitis (HE), also known as steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT), can be a debilitating manifestation of an autoimmune reaction against the thyroid that is often under-diagnosed primarily due to a lack of definitive diagnostic criteria. This is a case of a 52-year-old woman who has been diagnosed with HE after presenting with recurrent and severe psychosis in conjunction with paranoia and a thyroidopathy. Her symptoms are chronic, having first been documented as presenting 15 years prior and showing progressive exacerbation in both frequency and severity. The patient's paranoia often manifested as delusions involving family members or close friends and consequently introduced an opportunity for harm to herself and others. She showed great conviction with self-diagnoses that were proven incorrect, resulting in occasional non-compliance. Between episodes, the patient did not show evidence of symptoms. This patient struggled with several incorrect diagnoses and treatments for several years before the correct diagnosis of HE was made and displayed extreme improvement upon corticosteroid administration. This case illustrates the importance of increasing awareness of HE as well as including HE in a differential diagnosis when any patient presents with psychosis and concurrent thyroidopathy. Hashimoto's encephalitis follows putative characteristics of autoimmune diseases, exhibiting a higher incidence in women as compared to men, presenting with increased titers of autoantibodies, and showing dramatic amelioration when treated with corticosteroids.

  15. [Viral encephalitis. Experiences with 53 patients in Middle Hessia].

    PubMed

    Büttner, T; Dorndorf, W

    1988-10-01

    Clinical symptoms, course of disease, cerebrospinal fluid (CSF) and cranial CT of 53 patients suffering from acute or subacute encephalitis were evaluated retrospectively. The virus could be identified in 21 (39%) patients. Nine of them had herpes simplex virus-encephalitis. 16 patients, eight with herpes simplex virus-encephalitis, died due to the disease. Complete restitution could be observed in 73% of survivors. Disturbance of consciousness and severe focal neurological deficit worsened prognosis towards letality and functional recovery. Most patients had initially elevated number of cellular elements and/or pathological protein concentration in CSF. CSF protein profile showed disturbance of blood-CSF-barrier function in a great number of patients during the first week of the disease whereas autochthonous production of immunoglobulin G was observed predominantly during the second and third week. Elevated concentration of CSF-lactate was seen in herpes simplex virus-encephalitis and in letal cases. 28 (53%) patients had pathological CT-findings. Generalized brain edema, focal hypodensities, focal and cortical contrast enhancement and hemorrhagic imbibation were observed. With one exception patients with herpes simplex virus-encephalitis had hypodense lesions in the temporal lobe. Besides this CT-findings did not allow conclusions regarding the etiology of encephalitis. Prognosis of encephalitis caused by other than herpes simplex virus was worse in case of pathological CT.

  16. [Human Herpesvirus-6 Encephalitis in Allogeneic Hematopoietic Stem Cell Transplantation].

    PubMed

    Ogata, Masao

    2015-07-01

    The reactivation of human herpesvirus-6B (HHV-6B) is common after allogeneic hematopoietic cell transplantation (allo-HCT), and it is sporadically associated with the development of HHV-6 encephalitis. HHV-6 encephalitis typically develops around 2-6 weeks after allo-HCT, and it is characterized by short-term memory loss. Magnetic resonance imaging typically shows bilateral signal abnormalities in the limbic system. The incidence of HHV-6 encephalitis is reportedly 0-11.6% after bone marrow or peripheral blood stem cell transplantation and 4.9-21.4% after cord blood transplantation. The mortality of HHV-6 encephalitis is high, and survivors are often left with serious sequelae. Antiviral therapy using foscarnet or ganciclovir is recommended for the treatment of HHV-6 encephalitis, but the efficacy of the currently available treatment is insufficient once HHV-6 encephalitis has developed. The elucidation of the pathogenesis of HHV-6 encephalitis and the establishment of preventative therapy are needed to overcome this disease.

  17. Human cerebrospinal fluid monoclonal N-methyl-D-aspartate receptor autoantibodies are sufficient for encephalitis pathogenesis.

    PubMed

    Kreye, Jakob; Wenke, Nina K; Chayka, Mariya; Leubner, Jonas; Murugan, Rajagopal; Maier, Nikolaus; Jurek, Betty; Ly, Lam-Thanh; Brandl, Doreen; Rost, Benjamin R; Stumpf, Alexander; Schulz, Paulina; Radbruch, Helena; Hauser, Anja E; Pache, Florence; Meisel, Andreas; Harms, Lutz; Paul, Friedemann; Dirnagl, Ulrich; Garner, Craig; Schmitz, Dietmar; Wardemann, Hedda; Prüss, Harald

    2016-10-01

    SEE ZEKERIDOU AND LENNON DOI101093/AWW213 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a recently discovered autoimmune syndrome associated with psychosis, dyskinesias, and seizures. Little is known about the cerebrospinal fluid autoantibody repertoire. Antibodies against the NR1 subunit of the NMDAR are thought to be pathogenic; however, direct proof is lacking as previous experiments could not distinguish the contribution of further anti-neuronal antibodies. Using single cell cloning of full-length immunoglobulin heavy and light chain genes, we generated a panel of recombinant monoclonal NR1 antibodies from cerebrospinal fluid memory B cells and antibody secreting cells of NMDAR encephalitis patients. Cells typically carried somatically mutated immunoglobulin genes and had undergone class-switching to immunoglobulin G, clonally expanded cells carried identical somatic hypermutation patterns. A fraction of NR1 antibodies were non-mutated, thus resembling 'naturally occurring antibodies' and indicating that tolerance induction against NMDAR was incomplete and somatic hypermutation not essential for functional antibodies. However, only a small percentage of cerebrospinal fluid-derived antibodies reacted against NR1. Instead, nearly all further antibodies bound specifically to diverse brain-expressed epitopes including neuronal surfaces, suggesting that a broad repertoire of antibody-secreting cells enrich in the central nervous system during encephalitis. Our functional data using primary hippocampal neurons indicate that human cerebrospinal fluid-derived monoclonal NR1 antibodies alone are sufficient to cause neuronal surface receptor downregulation and subsequent impairment of NMDAR-mediated currents, thus providing ultimate proof of antibody pathogenicity. The observed formation of immunological memory might be relevant for clinical relapses.

  18. Behaviour disturbances during recovery from herpes simplex encephalitis.

    PubMed Central

    Greenwood, R; Bhalla, A; Gordon, A; Roberts, J

    1983-01-01

    Bizarre behaviour disturbances in four patients occurring during incomplete recovery from herpes simplex encephalitis are described. Some aspects of their behaviour were similar to that originally described by Klüver and Bucy in monkeys following bilateral temporal lobectomy. Previous reports of behavioural disturbances in man after herpes simplex encephalitis are reviewed and attention drawn to the aggressive and disruptive behaviour that is often seen. With the reduced mortality in herpes simplex encephalitis in recent years it is possible that behaviour disturbances such as those described here will be seen more frequently. Images PMID:6619889

  19. Development of a Genetically Engineered Venezuelan Equine Encephalitis Virus Vaccine

    DTIC Science & Technology

    1991-04-15

    antibody neutralization titers of sera from the TC-5A immunized horses ranged from 64 to > 128; however, the sera did not neutralize the equine virulent VEE...human adenovirus 5 DNA. Virology 52:456-467. Groot, H. 1972. The health and economic impact of Venezuelan equine encephalitis (VEE). p. 7-16. In... equine encephalitis (VEE). p. 7-16. In Venezuelan Encephalitis, Sci. Pub. 243, Pan American Health Organization, Washington, D.C. Hunt, A.R., Johnson, A.J

  20. Toxoplasmic Encephalitis with Untreated Hairy Cell Leukemia Variant

    PubMed Central

    Ikebe, Taichi; Sasaki, Hitohiro; Takata, Hiroyuki; Miyazaki, Yasuhiko; Ohtsuka, Eiichi; Saburi, Yoshio; Ogata, Masao; Shirao, Kuniaki

    2016-01-01

    Toxoplasmic encephalitis is a rare infectious complication in patients with hematological malignancy except for allogeneic hematopoietic stem cell transplantation (HSCT). We herein report a case of possible toxoplasmic encephalitis with untreated hairy cell leukemia variant. Magnetic resonance imaging showed multiple nodules with surrounding edema in the entire cerebrum. A polymerase chain reaction analysis for Toxoplasma gondii was negative. Her signs and symptoms fully recovered by empirical therapy with sulfadiazine and pyrimethamine. Toxoplasmic encephalitis may occur in patients who undergo non-allogeneic HSCT for hematological malignancies, even in those who have not been treated. PMID:27803415

  1. Japanese American Identity Dilemma.

    ERIC Educational Resources Information Center

    Maykovich, Minako K.

    The major theme of this book is the label "Quiet American" for the Japanese American. In order to locate Japanese Americans sociologically and psychologically in the structure of American society, various concepts such as "marginal man,""alienation," and "inauthenticity" are examined, specifying these…

  2. Incarcerating Japanese Americans.

    ERIC Educational Resources Information Center

    Daniels, Roger

    2002-01-01

    Presents the history of the Japanese American incarceration during World War II. Focuses on issues such as Executive Order 9066, what happened to the Japanese Americans during the war, and the forms of resistance that occurred. Questions whether something like this could ever happen again. (CMK)

  3. The Japanese American Story.

    ERIC Educational Resources Information Center

    Fukei, Budd

    This book presents a view of the Japanese American experience from the time of their immigration to this country in the 1800s to their acculturation into American society in the 1970s. Topics dealt with include the prejudice and mistrust experienced by the Japanese immigrants in this country, particularly their evacuation and internment in…

  4. The Japanese containerless experiments

    NASA Technical Reports Server (NTRS)

    Azuma, Hisao

    1990-01-01

    There are three sets of Japanese containerless experiments. The first is Drop dynamics research. It consists of acoustic levitation and large amplitude drop oscillation. The second is Optical materials processing in an acoustic levitation furnace. And the third is Electrostatic levitator development by two different Japanese companies.

  5. Severe Encephalitis in Cynomolgus Macaques Exposed to Aerosolized Eastern Equine Encephalitis Virus

    DTIC Science & Technology

    2007-08-01

    the illness. The onset of illness was dose dependent, but once a febrile response was observed, macaques were moribund within 36 h. Simultaneously, a...high mortality caused by a group of arboviruses found in the eastern half of North America and por- tions of Central and South America [1]. EEE viruses...encepha- litis (VEE) and western equine encephalitis (WEE) viruses, EEE viruses are mosquito transmitted and circulate through a natural reservoir

  6. Listeria monocytogenes encephalitis mimicking Herpes Simplex virus encephalitis: the differential diagnostic importance of cerebrospinal fluid lactic acid levels.

    PubMed

    Cunha, Burke A; Fatehpuria, Ritu; Eisenstein, Lawrence E

    2007-01-01

    Listeria monocytogenes is a common cause of bacterial meningitis in elderly patients and in those with impaired cellular immunity. The most common central nervous system infection caused by L. monocytogenes is acute bacterial meningitis; meningoencephalitis is uncommon and encephalitis is rare. Early diagnosis of L. monocytogenes meningitis is difficult because only 50% of cerebrospinal fluid (CSF) Gram stains are negative. L. monocytogenes is one of the few central nervous system pathogens associated with red blood cells in the CSF. When L. monocytogenes presents as encephalitis with red blood cells in the CSF, the clinical presentation mimics most closely herpes simplex virus (HSV)-1 encephalitis. Because the therapies for L. monocytogenes and HSV-1 are different, early diagnostic differentiation is clinically important. The CSF lactic acid is the best way to rapidly differentiate between these two entities; the CSF lactic acid level is elevated in L. monocytogenes but is not elevated in HSV-1 encephalitis. The case presented is an elderly man with chronic lymphocytic leukemia who presented with encephalitis. Advanced age and chronic lymphocytic leukemia predispose him to a wide variety of pathogens, but the rapidity and severity of his clinical presentation made L. monocytogenes and HSV-1 encephalitis the most likely diagnostic possibilities. The CSF Gram stain was negative, but the elevated CSF lactic acid levels with encephalitis and red blood cells in the CSF indicated L. monocytogenes as the most likely pathogen. We present a case of L. monocytogenes encephalitis mimicking HSV-1 encephalitis. While receiving ampicillin therapy, the patient remained unresponsive for more than 1 week and then suddenly regained consciousness and recovered without neurologic sequelae.

  7. MODERN JAPANESE, A BASIC READER. VOLUME II, JAPANESE TEXTS.

    ERIC Educational Resources Information Center

    HIBBETT, HOWARD; ITASAKA, GEN

    VOLUME II OF THIS INTRODUCTION TO WRITTEN JAPANESE CONTAINS 60 READING PASSAGES IN JAPANESE SCRIPT TO BE USED WITH THE VOCABULARY AND NOTES IN VOLUME I. THE READINGS ARE GRADED AND HAVE BEEN SELECTED TO REPRESENT GOOD MODERN JAPANESE USAGE. THE BEGINNING LESSONS ARE IN EASY INFORMAL STYLES AND ARE CONCERNED WITH THE JAPANESE LANGUAGE AND CULTURE.…

  8. Production of a Sindbis/Eastern Equine Encephalitis chimeric virus inactivated cell culture antigen.

    PubMed

    Goodman, C H; Russell, B J; Velez, J O; Laven, J J; Bagarozzi, D A; Moon, J L; Bedi, K; Johnson, B W

    2015-10-01

    Eastern Equine Encephalitis virus (EEEV) is a medically important pathogen that can cause severe encephalitis in humans, with mortality rates ranging from 30 to 80%. Unfortunately there are no antivirals or licensed vaccines available for human use, and laboratory diagnosis is essential to differentiate EEEV infection from other pathogens with similar clinical manifestations. The Arboviral Diseases Branch (ADB) reference laboratory at the CDC Division of Vector-Borne Diseases (DVBD) produces reference antigens used in serological assays such as the EEEV immunoglobulin M antibody-capture enzyme-linked immunosorbent assay (MAC-ELISA). However, EEEV is classified as a HHS select agent and requires biosafety level (BSL) three containment, limiting EEEV antigen production in non-select agent and BSL-2 laboratories. A recombinant Sindbis virus (SINV)/EEEV has been constructed for use under BSL-2 conditions and is not regulated as a select agent. Cell culture production of inactivated EEEV antigen from SINV/EEEV for use in the EEEV MAC-ELISA is reported here. Cell culture conditions and inactivation procedures were analyzed for SINV/EEEV using a recently developed antigen production algorithm, with the MAC-ELISA as the performance indicator.

  9. Noncytopathic Replication of Venezuelan Equine Encephalitis Virus and Eastern Equine Encephalitis Virus Replicons in Mammalian Cells

    PubMed Central

    Petrakova, Olga; Volkova, Eugenia; Gorchakov, Rodion; Paessler, Slobodan; Kinney, Richard M.; Frolov, Ilya

    2005-01-01

    Venezuelan equine encephalitis (VEE) and eastern equine encephalitis (EEE) viruses are important, naturally emerging zoonotic viruses. They are significant human and equine pathogens which still pose a serious public health threat. Both VEE and EEE cause chronic infection in mosquitoes and persistent or chronic infection in mosquito-derived cell lines. In contrast, vertebrate hosts infected with either virus develop an acute infection with high-titer viremia and encephalitis, followed by host death or virus clearance by the immune system. Accordingly, EEE and VEE infection in vertebrate cell lines is highly cytopathic. To further understand the pathogenesis of alphaviruses on molecular and cellular levels, we designed EEE- and VEE-based replicons and investigated their replication and their ability to generate cytopathic effect (CPE) and to interfere with other viral infections. VEE and EEE replicons appeared to be less cytopathic than Sindbis virus-based constructs that we designed in our previous research and readily established persistent replication in BHK-21 cells. VEE replicons required additional mutations in the 5′ untranslated region and nsP2 or nsP3 genes to further reduce cytopathicity and to become capable of persisting in cells with no defects in alpha/beta interferon production or signaling. The results indicated that alphaviruses strongly differ in virus-host cell interactions, and the ability to cause CPE in tissue culture does not necessarily correlate with pathogenesis and strongly depends on the sequence of viral nonstructural proteins. PMID:15919912

  10. Noncytopathic replication of Venezuelan equine encephalitis virus and eastern equine encephalitis virus replicons in Mammalian cells.

    PubMed

    Petrakova, Olga; Volkova, Eugenia; Gorchakov, Rodion; Paessler, Slobodan; Kinney, Richard M; Frolov, Ilya

    2005-06-01

    Venezuelan equine encephalitis (VEE) and eastern equine encephalitis (EEE) viruses are important, naturally emerging zoonotic viruses. They are significant human and equine pathogens which still pose a serious public health threat. Both VEE and EEE cause chronic infection in mosquitoes and persistent or chronic infection in mosquito-derived cell lines. In contrast, vertebrate hosts infected with either virus develop an acute infection with high-titer viremia and encephalitis, followed by host death or virus clearance by the immune system. Accordingly, EEE and VEE infection in vertebrate cell lines is highly cytopathic. To further understand the pathogenesis of alphaviruses on molecular and cellular levels, we designed EEE- and VEE-based replicons and investigated their replication and their ability to generate cytopathic effect (CPE) and to interfere with other viral infections. VEE and EEE replicons appeared to be less cytopathic than Sindbis virus-based constructs that we designed in our previous research and readily established persistent replication in BHK-21 cells. VEE replicons required additional mutations in the 5' untranslated region and nsP2 or nsP3 genes to further reduce cytopathicity and to become capable of persisting in cells with no defects in alpha/beta interferon production or signaling. The results indicated that alphaviruses strongly differ in virus-host cell interactions, and the ability to cause CPE in tissue culture does not necessarily correlate with pathogenesis and strongly depends on the sequence of viral nonstructural proteins.

  11. Recombinant allergens

    PubMed Central

    Jutel, Marek; Solarewicz-Madejek, Katarzyna; Smolinska, Sylwia

    2012-01-01

    Allergen specific immunotherapy (SIT) is the only known causative treatment of allergic diseases. Recombinant allergen-based vaccination strategies arose from a strong need to both to improve safety and enhance efficacy of SIT. In addition, new vaccines can be effective in allergies including food allergy or atopic dermatitis, which poorly respond to the current treatment with allergen extracts. A number of successful clinical studies with both wild-type and hypoallergenic derivatives of recombinant allergens vaccines have been reported for the last decade. They showed high efficacy and safety profile as well as very strong modulation of T and B cell responses to specific allergens. PMID:23095874

  12. [Two pediatric cases of anti-NMDA receptor antibody encephalitis].

    PubMed

    Ben Azoun, M; Tatencloux, S; Deiva, K; Blanc, P

    2014-11-01

    Although less frequent than viral encephalitis, anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a frequent form of acute pediatric encephalitis. After a prodromal phase of flu-like symptoms, psychiatric symptoms predominate - agitation, anxiety, hallucinations - and can make correct diagnosis more difficult. Also noted are abnormal dyskinesia and dystonia-like movements, partial seizures, difficulties talking or memorizing, and autonomic manifestations. The presentation of two cases of anti-NMDAR encephalitis illustrates the symptoms of this disease. Although the CSF abnormalities are not highly specific of this disease, and MRI most often normal, EEG shows more specific signs. These observations enable us to discuss different treatment options and understand the progression of this disease.

  13. Venezuelan Equine Encephalitis Virus, Southern Mexico

    PubMed Central

    Estrada-Franco, José G.; Navarro-Lopez, Roberto; Freier, Jerome E.; Cordova, Dionicio; Clements, Tamara; Moncayo, Abelardo; Kang, Wenli; Gomez-Hernandez, Carlos; Rodriguez-Dominguez, Gabriela; Ludwig, George V.

    2004-01-01

    Equine epizootics of Venezuelan equine encephalitis (VEE) occurred in the southern Mexican states of Chiapas in 1993 and Oaxaca in 1996. To assess the impact of continuing circulation of VEE virus (VEEV) on human and animal populations, serologic and viral isolation studies were conducted in 2000 to 2001 in Chiapas State. Human serosurveys and risk analyses indicated that long-term endemic transmission of VEEV occurred among villages with seroprevalence levels of 18% to 75% and that medical personnel had a high risk for VEEV exposure. Seroprevalence in wild animals suggested cotton rats as possible reservoir hosts in the region. Virus isolations from sentinel animals and genetic characterizations of these strains indicated continuing circulation of a subtype IE genotype, which was isolated from equines during the recent VEE outbreaks. These data indicate long-term enzootic and endemic VEEV circulation in the region and continued risk for disease in equines and humans. PMID:15663847

  14. Prospects for cannabinoid therapies in viral encephalitis.

    PubMed

    Solbrig, Marylou V; Fan, Yijun; Hazelton, Paul

    2013-11-06

    Cannabinoids are promising therapies to support neurogenesis and decelerate disease progression in neuroinflammatory and degenerative disorders. Whether neuroprotective effects of cannabinoids are sustainable during persistent viral infection of the CNS is not known. Using a rodent model of chronic viral encephalitis based on Borna Disease (BD) virus, in which 1 week treatment with the general cannabinoid WIN 55,212-2 has been shown to be neuroprotective (Solbrig et al., 2010), we examine longer term (2 week treatment) effects of a general (CB1 and CB2) cannabinoid receptor agonist WIN55,212-2 (1mg/kg ip twice per day) or a specific (CB2) cannabinoid receptor agonist HU-308 (5mg/kg ip once daily) on histopathology, measures of frontostriatal neurogenesis and gliogenesis, and viral load. We find that WIN and HU-308 differ in their ability to protect new BrdU(+) cells. The selective CB2 agonist HU increases BrdU(+) cells in prefrontal cortex (PFC), significantly increases BrdU(+) cells in striatum, differentially regulates polydendrocytes vs. microglia/macrophages, and reduces immune activation at a time WIN-treated rats appear tolerant to the anti-inflammatory effect of their cannabinoid treatment. WIN and HU had little direct viral effect in PFC and striatum, yet reduced viral signal in hippocampus. Thus, HU-308 action on CB2 receptors, receptors known to be renewed during microglia proliferation and action, is a nontolerizing mechanism of controlling CNS inflammation during viral encephalitis by reducing microglia activation, as well as partially limiting viral infection, and uses a nonpsychotropic cannabinoid agonist.

  15. Recombinant gonadotropins.

    PubMed

    Lathi, R B; Milki, A A

    2001-10-01

    Recombinant DNA technology makes it possible to produce large amounts of human gene products for pharmacologic applications, supplanting the need for human tissues. The genes for the alpha and beta subunits of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and human chorionic gonadotropin (hCG) have been characterized and cloned. Recombinant FSH (rFSH) has been shown to be safe and effective in the treatment of fertility disorders. In comparison with the urinary gonadotropin products, human menopausal gonadotropins (HMG), and urinary follitropins (uFSH), rFSH is more potent and better tolerated by patients. Recombinant HCG appears to be as efficacious as urinary HCG with the benefit of improved local tolerance. Recombinant LH (rLH) is likely to be recommended as a supplement to rFSH for ovulation induction in hypogonadotropic women. It may also benefit in vitro fertilization patients undergoing controlled ovarian hyperstimulation with rFSH combined with pituitary suppression, with a gonadotropin-releasing hormone agonist or antagonist.

  16. Spectrum Recombination.

    ERIC Educational Resources Information Center

    Greenslade, Thomas B., Jr.

    1984-01-01

    Describes several methods of executing lecture demonstrations involving the recombination of the spectrum. Groups the techniques into two general classes: bringing selected portions of the spectrum together using lenses or mirrors and blurring the colors by rapid movement or foreshortening. (JM)

  17. Fifteen minute consultation: Managing neonatal and childhood herpes encephalitis

    PubMed Central

    Le Doare, K; Menson, Esse; Patel, Deepak; Lim, Ming; Lyall, Hermione; Herberg, Jethro

    2015-01-01

    Herpes simplex encephalitis (HSE) is the most common single cause of viral encephalitis in infants and children. Treated or untreated, it can be associated with considerable morbidity and mortality, and its presentation is usually insidious and non-specific. Prompt and careful investigation is important in order to establish the diagnosis so that treatment can be optimised. We address some common questions arising when diagnosing and treating presumed HSE throughout childhood. PMID:25112286

  18. Development of a Genetically Engineered Venezuelan Equine Encephalitis Virus Vaccine

    DTIC Science & Technology

    1988-12-20

    immunization, the horses will be returned to the large animal biocontainment facility to be challenged with equine virulent VEE virus. The animals will be...AD £IT FiLE C p DEVELOPMENT OF A GENETICALLY ENGINEERED VENEZUELAN EQUINE ENCEPHALITIS VIRUS VACCINE ANNUAL REPORT to DENNIS W. TRENT 0DECEMBER 20...Engineered Venezuelan Equine Encephalitis Virus Vaccine 12. PERSONAL AUTHOR(S) Dennis W. Trent 13a. TYPE OF REPORT 13b. TIME COVERED 14. DATE OF REPORT

  19. A vaccine candidate for eastern equine encephalitis virus based on IRES-mediated attenuation

    PubMed Central

    Pandya, Jyotsna; Gorchakov, Rodion; Wang, Eryu; Leal, Grace; Weaver, Scott C.

    2012-01-01

    To develop an effective vaccine against eastern equine encephalitis (EEE), we engineered a recombinant EEE virus (EEEV) that was attenuated and capable of replicating only in vertebrate cells, an important safety feature for live vaccines against mosquito-borne viruses. The subgenomic promoter was inactivated with 13 synonymous mutations and expression of the EEEV structural proteins was placed under the control of an internal ribosomal entry site (IRES) derived from encephalomyocarditis virus (EMCV). We tested this vaccine candidate for virulence, viremia and efficacy in the murine model. A single subcutaneous immunization with 104 infectious units protected 100% of mice against intraperitoneal challenge with a highly virulent North American EEEV strain. None of the mice developed any signs of disease or viremia after immunization or following challenge. Our findings suggest that the IRES-based attenuation approach can be used to develop a safe and effective vaccine against EEE and other alphaviral diseases. PMID:22222869

  20. A vaccine candidate for eastern equine encephalitis virus based on IRES-mediated attenuation.

    PubMed

    Pandya, Jyotsna; Gorchakov, Rodion; Wang, Eryu; Leal, Grace; Weaver, Scott C

    2012-02-08

    To develop an effective vaccine against eastern equine encephalitis (EEE), we engineered a recombinant EEE virus (EEEV) that was attenuated and capable of replicating only in vertebrate cells, an important safety feature for live vaccines against mosquito-borne viruses. The subgenomic promoter was inactivated with 13 synonymous mutations and expression of the EEEV structural proteins was placed under the control of an internal ribosomal entry site (IRES) derived from encephalomyocarditis virus (EMCV). We tested this vaccine candidate for virulence, viremia and efficacy in the murine model. A single subcutaneous immunization with 10(4) infectious units protected 100% of mice against intraperitoneal challenge with a highly virulent North American EEEV strain. None of the mice developed any signs of disease or viremia after immunization or following challenge. Our findings suggest that the IRES-based attenuation approach can be used to develop a safe and effective vaccine against EEE and other alphaviral diseases.

  1. [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.

  2. Cortical hypometabolism demonstrated by PET in relapsing NMDA receptor encephalitis.

    PubMed

    Pillai, Sekhar C; Gill, Deepak; Webster, Richard; Howman-Giles, Robert; Dale, Russell C

    2010-09-01

    N-methyl-d-aspartate (NMDA) receptor encephalitis is a newly defined type of autoimmune encephalitis. Two girls (age 3 years, case 1, and 7 years, case 2) with relapsing NMDA receptor encephalitis each had the classic clinical features of encephalopathy, movement disorders, psychiatric symptoms, seizures, insomnia, and mild autonomic dysfunction. Both patients had persistent neuropsychiatric disability, despite immune therapies. Positron emission tomography (PET) scans were performed during clinical relapse at 6 weeks (case 1) and 5 months (case 2). In both cases, the scans demonstrated reduced fluorodeoxyglucose metabolism in the cerebral cortex, with the temporal regions being most affected. PET imaging was more sensitive than magnetic resonance imaging in these patients. In contrast, the one previous report of acute NMDA receptor encephalitis indicated cortical hypermetabolism. Thus, NMDA receptor encephalitis may be associated with variable PET findings, possibly dependent upon the timing of the study, or other factors. Future studies should investigate whether cortical hypometabolism is associated with a relapsing course, and whether it is predictive of a poorer outcome in NMDA receptor encephalitis.

  3. [Two cases of anti-NMDA receptor encephalitis].

    PubMed

    Nakamura, Kazue; Takahashi, Tsutomu; Matsuoka, Tadasu; Kido, Mikio; Uehara, Takashi; Suzuki, Michio

    2011-01-01

    Anti-NMDA receptor encephalitis, reported by Dalmau et al., is a paraneoplastic encephalitis frequently associated with ovarian teratoma. After the manifestation of schizophrenia-like psychotic symptoms in the initial stage, serious neurological symptoms such as convulsions and central hypoventilation develop. We report two cases of 17-year-old girls with anti-NMDA receptor encephalitis who exhibited different clinical courses. Case 1 showed a typical course of anti-NMDA receptor encephalitis associated with sustained consciousness disturbance requiring long-term artificial respiration. Case 2 underwent surgery for an ovarian teratoma in the early stages of the disorder, did not show convulsions or central hypoventilation, and recovered without any sequelae. Early resection of the ovarian teratoma and the immune suppression therapy may have contributed to the rapid recovery and favorable outcome in case 2. Psychiatrists are the first to see a majority of patients with anti-NMDA receptor encephalitis because of psychiatric symptoms and behavioral changes observed in the initial stage. For successful treatment, psychiatrists need to cooperate with neurologists and gynecologists early in the course of this disorder. Psychiatrists' knowledge of the symptoms and clinical course of this form of encephalitis is essential for early detection and adequate treatment, which may be life-saving and contribute to good functional outcomes.

  4. 2011 Japanese Nuclear Incident

    EPA Pesticide Factsheets

    EPA’s RadNet system monitored the environmental radiation levels in the United States and parts of the Pacific following the Japanese Nuclear Incident. Learn about EPA’s response and view historical laboratory data and news releases.

  5. How the Japanese work.

    PubMed

    Chambers, D W

    1998-01-01

    The Japanese do not work harder or even use different approaches so much as they aim for a different result--one that balances process and results and extends the definition of quality beyond the product itself to include cost and convenience to the customer as well. Ten methods of the Japanese kaizen culture of work are presented with applications and contrasts to American dentistry.

  6. Persistent West Nile virus transmission and the apparent displacement St. Louis encephalitis virus in southeastern California, 2003-2006.

    PubMed

    Reisen, William K; Lothrop, Hugh D; Wheeler, Sarah S; Kennsington, Marc; Gutierrez, Arturo; Fang, Ying; Garcia, Sandra; Lothrop, Branka

    2008-05-01

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

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

    PubMed Central

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

    2008-01-01

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

  8. Japanese Encephalitis—A Pathological and Clinical Perspective

    PubMed Central

    Ghosh, Debapriya; Basu, Anirban

    2009-01-01

    Japanese encephalitis (JE) is the leading form of viral encephalitis in Asia. It is caused by the JE virus (JEV), which belongs to the family Flaviviridae. JEV is endemic to many parts of Asia, where periodic outbreaks take hundreds of lives. Despite the catastrophes it causes, JE has remained a tropical disease uncommon in the West. With rapid globalization and climatic shift, JEV has started to emerge in areas where the threat was previously unknown. Scientific evidence predicts that JEV will soon become a global pathogen and cause of worldwide pandemics. Although some research documents JEV pathogenesis and drug discovery, worldwide awareness of the need for extensive research to deal with JE is still lacking. This review focuses on the exigency of developing a worldwide effort to acknowledge the prime importance of performing an extensive study of this thus far neglected tropical viral disease. This review also outlines the pathogenesis, the scientific efforts channeled into develop a therapy, and the outlook for a possible future breakthrough addressing this killer disease. PMID:19787040

  9. Anti-NMDA Receptor antibody encephalitis with concomitant detection of Varicella zoster virus.

    PubMed

    Solís, Natalia; Salazar, Lucrecia; Hasbun, Rodrigo

    2016-10-01

    The typical presentation of anti-NMDA (N-Methyl-d-Aspartate) receptor encephalitis involves young women with psychiatric, neurologic and autonomic symptoms; it is often associated with mature ovarian teratomas. NMDA receptor encephalitis has been described following Herpes simplex virus (HSV) encephalitis. This case describes a classic presentation of anti-NMDA receptor encephalitis with the concomitant presence of Varicella zoster virus in the cerebrospinal fluid.

  10. Multiple linear epitopes (B-cell, CTL and Th) of JEV expressed in recombinant MVA as multiple epitope vaccine induces a protective immune response.

    PubMed

    Wang, Fengjuan; Feng, Xiuli; Zheng, Qisheng; Hou, Hongyan; Cao, Ruibing; Zhou, Bin; Liu, Qingtao; Liu, Xiaodong; Pang, Ran; Zhao, Jin; Deng, Wenlei; Chen, Puyan

    2012-09-17

    Epitope-based vaccination might play an important role in the protective immunity against Japanese encephalitis virus (JEV) infection. The purpose of the study is to evaluate the immune characteristics of recombinant MVA carrying multi-epitope gene of JEV (rMVA-mep). The synthetic gene containing critical epitopes (B-cell, CTL and Th) of JEV was cloned into the eukaryotic expression vector pGEM-K1L, and the rMVA-mep was prepared. BALB/c mice were immunized with different dosages of purified rMVA-mep and the immune responses were determined in the form of protective response against JEV, antibodies titers (IgG1 and IgG2a), spleen cell lymphocyte proliferation, and the levels of interferon-γ and interleukin-4 cytokines. The results showed that live rMVA-mep elicited strongly immune responses in dose-dependent manner, and the highest level of immune responses was observed from the groups immunized with 107 TCID50 rMVA-mep among the experimental three concentrations. There were almost no difference of cytokines and neutralizing antibody titers among 107 TCID50 rMVA-mep, recombinant ED3 and inactivated JEV vaccine. It was noteworthy that rMVA-mep vaccination potentiates the Th1 and Th2-type immune responses in dose-dependent manner, and was sufficient to protect the mice survival against lethal JEV challenge. These findings demonstrated that rMVA-mep can produce adequate humoral and cellular immune responses, and protection in mice, which suggested that rMVA-mep might be an attractive candidate vaccine for preventing JEV infection.

  11. Geographic dynamics of viral encephalitis in Thailand.

    PubMed

    Henrich, Timothy J; Hutchaleelaha, Sombat; Jiwariyavej, Vitaya; Barbazan, Philippe; Nitatpattana, Narong; Yoksan, Sutee; Gonzalez, Jean-Paul

    2003-06-01

    Viral encephalitis (VE) continues to be a major disease in Asia, causing serious illness which may result in death or have neurological sequelae. This study involves an ecological analysis of the climatic, geographic and seasonal patterns of clinically reported VE in Thailand from 1993 to 1998 to investigate regional and seasonal differences in disease incidence. Three thousand eight hundred and twenty nine cases of VE were clinically diagnosed nationwide during the study period by the Thai Ministry of Public Health. Spearman rank correlations of temporal, spatial and geographic variables with disease incidence were performed. The monthly incidence of VE correlated significantly with seasonal changes in temperature, relative humidity and rainfall in the north-northeast region of Thailand (P < 0.001), whereas incidence in the south-central region correlated only with relative humidity (P = 0.003). Spatial analysis revealed a positive correlation of disease with elevation (P < 0.001), and negative correlations with rice-field cover (P < 0.001), agricultural land-use (P < 0.001) and temperature (P = 0.004) in the north-northeast region. No significant spatial correlation was identified in the south-central region. The spatial distribution of VE suggests that etiologic variations may be responsible, in part, for the geographic patterns of disease. Active etiologic surveillance is necessary in a variety of geographic settings in order to provide physicians with information necessary for disease prevention and clinical management.

  12. THE PATHOGENESIS OF HERPES VIRUS ENCEPHALITIS

    PubMed Central

    Johnson, Richard T.

    1964-01-01

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

  13. Tick-borne encephalitis in eastern France.

    PubMed

    Hansmann, Yves; Pierre Gut, Jean; Remy, Veronique; Martinot, Martin; Allard Witz, Marie; Christmann, Daniel

    2006-01-01

    Each y a few cases of TBE infection are described in Alsace, France which lies at the occidental limit of the endemic zone of tick-borne encephalitis (TBE). Hence we carried out a retrospective epidemiological and clinical study of TBE infection in Alsace. Data were collected from serological results sent to the Institut de Virologie (Université Louis Pasteur) in Strasbourg. All samples positive for specific IgM against TBE were retained. The physician in charge of each patient was asked to provide clinical, epidemiological and biological data and with his agreement the medical file was referred to us. Since 1968, 64 cases of TBE infection, occurring between April and November, had been described. In 56% of cases, flu-like symptoms preceded neurological symptoms. Most patients had meningitis (54%) or meningoencephalitis (34%). There was no death due to TBE. Two areas were more highly endemic for the disease: the Guebwiller valley in low mountain country and the Neuhof forest, near Strasbourg in the plain of Alsace. In the last 2 y of the study, a third zone seemed to emerge, in the Munster valley. This epidemiological survey revealed the existence in Alsace of 2 endemic zones of TBE with a third zone possibly emerging in the last few y. The survey must be continued to follow the evolution of the disease.

  14. Henipavirus Encephalitis: Recent Developments and Advances.

    PubMed

    Ong, Kien Chai; Wong, Kum Thong

    2015-09-01

    The genus Henipavirus within the family Paramyxoviridae includes the Hendra virus (HeV) and Nipah virus (NiV) which were discovered in the 1990s in Australia and Malaysia, respectively, after emerging to cause severe and often fatal outbreaks in humans and animals. While HeV is confined to Australia, more recent NiV outbreaks have been reported in Bangladesh, India and the Philippines. The clinical manifestations of both henipaviruses in humans appear similar, with a predominance of an acute encephalitic syndrome. Likewise, the pathological features are similar and characterized by disseminated, multi-organ vasculopathy comprising endothelial infection/ulceration, vasculitis, vasculitis-induced thrombosis/occlusion, parenchymal ischemia/microinfarction, and parenchymal cell infection in the central nervous system (CNS), lung, kidney and other major organs. This unique dual pathogenetic mechanism of vasculitis-induced microinfarction and neuronal infection causes severe tissue damage in the CNS. Both viruses can also cause relapsing encephalitis months and years after the acute infection. Many animal models studied to date have largely confirmed the pathology of henipavirus infection, and provided the means to test new therapeutic agents and vaccines. As the bat is the natural host of henipaviruses and has worldwide distribution, spillover events into human populations are expected to occur in the future.

  15. Eastern equine encephalitis: a classical case.

    PubMed

    Baig, Basarat; Mehta, Tapan; Khalid, Nauman; Chhabra, Lovely

    2014-10-01

    We present the case of a 40-year-old man with rapidly deteriorating acute meningoencephalitis, finally diagnosed as eastern equine encephalitis (EEE). The course and timing in this patient are quite characteristic. EEE is an arthropod borneviral illness in which the mosquito serves as the vector. It is amongst the most severe of the arbovirus encephalitides and has a high mortality and morbidity. In nonfatal cases, residual neurological deficits are often severe and permanent. North American lineage of EEE is mainly found in the northeast especially along the coastal areas. EEE is primarily found in horses and other domestic mammals that remain outdoors nocturnally. In humans, symptoms range from nonspecific constitutional features to catastrophic neurological sequelae including death. Hyponatremia and increased cerebrospinal fluid (CSF) white blood cell count are independent predictors of poor outcomes. Diagnosis is suggestive by demonstrating IgM antibody in blood or CSF samples and can be confirmed by other serologic assay including immunohistochemistry and polymerase chain reaction (PCR). Measures recommended by the Center for Disease Control (CDC) for prevention include using repellents, protective clothing, screens, and eradication of mosquito breeding areas. EEE remains without cure and prevention is the best medicine.

  16. [Anti-NMDA-receptor encephalitis. An interdisciplinary clinical picture].

    PubMed

    Prüss, H; Dalmau, J; Arolt, V; Wandinger, K-P

    2010-04-01

    Anti-NMDA-receptor encephalitis is a severe and considerably underdiagnosed form of encephalitis with characteristic clinical features including psychiatric symptoms, decreased levels of consciousness, hypoventilation, epileptic seizures, autonomic dysfunction and dyskinesias. Most patients are primarily seen by psychiatrists, often on the assumption of a drug-induced psychosis. Anti-NMDA-receptor encephalitis had initially been described in young women with ovarian teratoma, but is also common in women without tumour, in men and in children. The diagnosis is based on the characteristic clinical picture, supporting findings of brain MRI, electroencephalogram and cerebrospinal fluid (CSF), and the presence of highly specific autoantibodies directed against the NR1 subunit of NMDA-type glutamate receptors in the serum or CSF. In particular, anti-NMDA-receptor encephalitis must be excluded in patients with 'encephalitis of unknown cause'. In principle, the prognosis is favourable and recovery from symptoms can be expected even after prolonged intensive care treatment and mechanical ventilation. However, improvement correlates with prompt identification of the disorder, early immunotherapy and - in the case of a malignancy - with complete tumour removal. Patient care requires an interdisciplinary approach including neurologists, psychiatrists, paediatricians, oncologists and gynaecologists.

  17. Entry and Replication of Japanese Encephalitis Virus in Cultured Neurogenic Cells

    DTIC Science & Technology

    1990-07-01

    acetylcholine receptor a rabies virus receptor ). Science, 215, 211-221. 214 Longberg-Holm, K. and...At present. little is known about neuronal receptors for various neurotropic viruses . Acetylcholine receptors are suspected to function as receptors ...for rabies virus (Lentz et al., 1982; Burrage et al., 1985). In the search for the neuronal receptors for JE virus , the hybrid cells and

  18. Comparative Study of Mouse Brains Infected with Japanese Encephalitis Virus by Intracerebral or Intraperitoneal Inoculation

    DTIC Science & Technology

    1990-07-01

    certain percentage of mice zumi & Tsubo 1965: Oyanagi et al. 1969: following a more prolonged disease course. Hase et al. i 99o). Furthermore. recent...result of viral replication is not the duration of disease or the route of prominent: therefore, it is thought that func- infection influences the...Zeiss SM i 0) or Philips leucocytic infiltration that involved both the CM 12 electron microscope. leptomeninges and the brain tissue (Fig. iC.D

  19. Isolation of Japanese Encephalitis Virus Strains from Sentinel Pigs in Northern Thailand, 1982

    DTIC Science & Technology

    1985-01-01

    3 lymphadenopathy was noted for several days. A TANO.i LAORAKPONGSE’ second bone marrow puncture performed on 6th September showed Leishmania . Depts...showed no Leishmania . However, as the Station, 395 Hatfield Road, St. Albans, AL4 OXU; patient’s hepatic biochemistry was not yet normal, a 4Kampangphet...Thailand. VI. Summary and conclusions. American confirmed L. donovani infection before May 1983. Journal of Epidemiologv, 100, 69-76. These data

  20. [Two cases of herpes encephalitis with normal cerebrospinal fluid findings].

    PubMed

    Avkan Oğuz, Vildan; Yapar, Nur; Sezak, Nurbanu; Alp Cavuş, Sema; Kuruüzüm, Ziya; Sayiner, Arzu; Ada, Emel; Cakir, Nedim; Yüce, Ayşe

    2006-01-01

    In this report, characteristics of two cases of Herpes simplex virus (HSV) encephalitis with normal cerebrospinal fluid (CSF) findings at the time of admission have been discussed and the current literature has been reviewed. The diagnosis of the cases (one was 23 years old male, and the other was 75 years old female patient) was made on the magnetic resonance imaging (MRI) findings concordant with HSV encephalitis, together with HSV-1 DNA positivity by polymerase chain reaction (PCR). Both of the patients were treated with acyclovir (3 x 750 mg/day) lasting for 15 days and 21 days, respectively. The first male patient recovered with mild neurological defects, whereas the second female patient died because of nosocomial pneumonia and septicemia. In conclusion, even the CSF findings are normal, in cases considered to be HSV encephalitis, MRI should be the first radiological diagnostic step and the diagnosis should be confirmed by the detection of HSV DNA in CSF by PCR.

  1. Primary amoebic meningo-encephalitis due to Naegleria fowleri.

    PubMed

    Jain, Ragini; Tilak, Vijai

    2011-07-01

    Primary amoebic meningo-encephalitis is a fulminant, often rapidly fatal infection affecting individuals with a recent history of swimming in warm fresh water. A fatal case of primary amoebic meningoencephalitis due to Naegleria fowleri in a 35 years old male suffering from human immunodeficiency virus with pulmonary tuberculosis infection is reported. Naegleria fowleri was diagnosed by wet mount examination of cerebrospinal fluid and the diagnosis was confirmed by culture of the cerebrospinal fluid on non-nutrient agar layered with Escherichia coli. The patient was treated with amphotericin B and antituberculous treatment but the outcome was fatal. Primary amoebic meningo-encephalitis should be suspected in every case of pyogenic meningo-encephalitis in which no bacteria or fungus is found on cerebrospinal fluid examination.

  2. West Nile virus encephalitis with myositis and orchitis.

    PubMed

    Smith, Roger D; Konoplev, Sergiej; DeCourten-Myers, Gabrielle; Brown, Thomas

    2004-02-01

    This report documents the hospital course and autopsy findings of a 43-year-old man with a renal allograft who died of West Nile virus (WNV) encephalitis. Central nervous system (CNS) findings were those of severe necrotizing and hemorrhagic encephalitis affecting gray matter regions limited to the diencepahlon, rhombencephalon, spinal cord, and limbic system. The bilateral process exhibited preferential involvement of motor neurons. Brain imaging obtained 6 days before death demonstrated an unusual pattern of involvement corresponding with the autopsy findings, confirming that imaging may be a specific diagnostic guide in WNV encephalitis. Extra-CNS findings include myositis with T-lymphocyte infiltration of nerve fibers, suggesting that the virus may reach the CNS via peripheral nerves. Orchitis with dense T-lymphocyte infiltration and syncytial cell formation thought to be due to WNV were also noted.

  3. Diagnosis of Jamestown Canyon encephalitis by polymerase chain reaction.

    PubMed

    Huang, C; Campbell, W; Grady, L; Kirouac, I; LaForce, F M

    1999-06-01

    In recent years, polymerase chain reaction (PCR) has been under study as a potential technique to improve the accuracy of diagnosis of suspected central nervous system viral infections. We describe a case of severe encephalitis in a previously healthy 20-year-old woman from New York who presented with headache, fever, and photophobia. Her illness was characterized by progressive worsening of her neurological status, leading to confusion, delirium, and status epilepticus. The diagnosis of Jamestown Canyon encephalitis was established by positive reverse transcriptase (RT)-PCR and nucleic acid sequencing of the band from both cerebrospinal fluid and brain tissue. The nucleotide sequence and the deduced amino acid sequence of the Jamestown Canyon virus from this patient were very similar to Jamestown Canyon virus isolates from mosquito pools in New York. This report suggests that RT-PCR assays could be important tools in the diagnostic workup of cases of encephalitis.

  4. Epstein-Barr Virus Encephalitis: A Case Report

    PubMed Central

    HASHEMIAN, Somayh; ASHRAFZADEH, Farah; AKHONDIAN, Javad; BEIRAGHI TOOSI, Mehran

    2015-01-01

    Many neurologic manifestations of Epstein-Barr virus (EBV) infection have been documented, including encephalitis, aseptic meningitis, transverse myelitis, and Guillain-Barre syndrome. These manifestations can occur alone or coincidentally with the clinical picture of infectious mononucleosis. EBV encephalitis is rare and is indicated as a wide range of clinical manifestations. We report a 10-year-old girl presented with fever, gait disturbance, and bizarre behavior for one week. The results of the physical examination were unremarkable. The diagnosis of EBV encephalitis was made by changes in titers of EBV specific antibodies and MRI findings. A cranial MRI demonstrated abnormal high signal intensities in the basal ganglia and the striatal body, especially in the putamen and caudate nucleus. EBV infection should be considered when lesions are localized to the basal ganglia. PMID:25767548

  5. Neuroleptic intolerance in patients with anti-NMDAR encephalitis

    PubMed Central

    Lejuste, Florian; Thomas, Laure; Picard, Géraldine; Desestret, Virginie; Ducray, François; Rogemond, Veronique; Psimaras, Dimitri; Antoine, Jean-Christophe; Delattre, Jean-Yves; Groc, Laurent; Leboyer, Marion

    2016-01-01

    Objective: To precisely describe the initial psychiatric presentation of patients with anti-NMDA receptor (NMDAR) antibodies encephalitis (anti-NMDAR encephalitis) to identify potential clues enhancing its early diagnosis. Methods: We retrospectively studied the French Reference Centre medical records of every adult patient with anti-NMDAR encephalitis to specify the patients' initial psychiatric symptoms leading to hospitalization in a psychiatric department and the reasons underlying the diagnosis of anti-NMDAR encephalitis. Results: The medical records of 111 adult patients were reviewed. Psychiatric features were the initial presentation in 65 patients (59%). Among them, several psychiatric manifestations were observed, including visual and auditory hallucinations (n = 26, 40%), depression (n = 15, 23%), mania (n = 5, 8%), acute schizoaffective episode (n = 15, 23%), and eating disorder or addiction (n = 4; 6%). Forty-five patients (40% of total cohort) were first hospitalized in a psychiatric institution (91% women), with a median duration of stay of 9 days (range 0.25–239 days). Among them, 24 patients (53%) had associated discreet neurologic signs at the first evaluation, while 17 additional patients (38%) developed neurologic signs within a few days. Twenty-one patients (47%) were transferred to a medical unit for a suspicion of antipsychotic intolerance characterized by high temperature, muscle rigidity, mutism or coma, and biological results suggesting rhabdomyolysis. Conclusions: Several psychiatric presentations were observed in patients with anti-NMDAR encephalitis, although none was specific; however, patients, mostly women, also had discreet neurologic signs that should be carefully assessed as well as signs of antipsychotic intolerance that should raise suspicion for anti-NMDAR encephalitis. PMID:27606355

  6. Roseolovirus-associated encephalitis in immunocompetent and immunocompromised individuals.

    PubMed

    Ongrádi, Joseph; Ablashi, Dharam V; Yoshikawa, Tetsushi; Stercz, Balázs; Ogata, Masao

    2017-02-01

    The roseoloviruses, human herpesvirus (HHV)-6A, HHV-6B, and HHV-7, can cause severe encephalitis or encephalopathy. In immunocompetent children, primary HHV-6B infection is occasionally accompanied by diverse clinical forms of encephalitis. Roseolovirus coinfections with heterologous viruses and delayed primary HHV-7 infection in immunocompetent adults result in very severe neurological and generalized symptoms. Recovery from neurological sequelae is slow and sometimes incomplete. In immunocompromised patients with underlying hematological malignancies and transplantation, frequent single or simultaneous reactivation of roseoloviruses elicit severe, lethal organ dysfunctions, including damages in the limbic system, brain stem, and hippocampus. Most cases have been due to HHV-6B with HHV-6A accounting for 2-3%. The most severe manifestation of HHV-6B reactivation is post-transplantation limbic encephalitis. Seizures, cognitive problems, and abnormal EEG are common. Major risk factors for HHV-6B-associated encephalitis include unrelated cord blood cell transplantation and repeated hematopoietic stem cell transplantation. Rare genetic disorders, male gender, certain HLA constellation, and immune tolerance to replicating HHV-6 in persons carrying chromosomally integrated HHV-6 might also predispose an individual to roseolovirus-associated brain damage. At this time, little is known about the risk factors for HHV-7-associated encephalitis. Intrathecal glial cell destruction due to virus replication, overexpression of proinflammatory cytokines, and viral mimicry of chemokines all contribute to brain dysfunction. High virus load in the cerebrospinal fluid, hippocampal astrogliosis, and viral protein expression in HHV-6B-associated cases and multiple microscopic neuronal degeneration in HHV-7-associated cases are typical laboratory findings. Early empirical therapy with ganciclovir or foscarnet might save the life of a patient with roseolovirus-associated encephalitis.

  7. Herpes simplex virus type 1 encephalitis in acquired immunodeficiency syndrome.

    PubMed

    Chrétien, F; Bélec, L; Hilton, D A; Flament-Saillour, M; Guillon, F; Wingertsmann, L; Baudrimont, M; de Truchis, P; Keohane, C; Vital, C; Love, S; Gray, F

    1996-10-01

    Herpes simplex (HSV) infection of the central nervous system is uncommon in AIDS and usually has an atypical topography. This review is centred around the case of a 49-year-old homosexual patient with AIDS who died from diffuse encephalopathy. Neuropathological examination revealed necrotic and haemorrhagic changes involving both temporal lobes, insulae and cingulate gyri. Cowdry type A intranuclear inclusion bodies were abundant but inflammation was minimal. Electron microscopy confirmed characteristic herpes virus particles. Immunocyto-chemistry was positive for HSV type 1 and 2. In situ hybridization and PCR, however, were positive for HSV type 1 but excluded HSV type 2. There was associated cytomegalovirus ventriculitis but clearly separated from HSV encephalitis. There were no histological features of HIV encephalitis and HIV could not be demonstrated by immunocytochemistry or by PCR to demonstrate proviral DNA. Apoptotic neurons were numerous in areas with a severe macrophage reaction. Only two pathological cases with characteristic limbic distribution and necrotic haemorrhagic histologic have been reported previously. The rarity of these reports suggests that in advanced AIDS, the immune reaction causing a typical necrotizing encephalitis cannot be mounted. Distinction between HSV type 1 and 2 infection may be difficult by immunocytochemistry and usually requires in situ hybridization, tissue culture or PCR. In AIDS patients, HSV-1 has been identified as responsible for encephalitis whereas HSV-2 has been more responsible for myelitis. Associated productive HIV infection of the CNS was found in none of the cases. In contrast, cytomegalovirus encephalitis was found in nine of 11 cases of AIDS-associated HSV encephalitis.

  8. Luxury perfusion phenomenon in acute herpes simplex virus encephalitis.

    PubMed

    Tanaka, M; Uesugi, M; Igeta, Y; Kondo, S; Sun, X; Hirai, S

    1995-02-01

    In a patient with acute herpes simplex virus (HSV) encephalitis, positron emission tomography (PET) demonstrated increased cerebral blood flow in the affected temporal lobe accompanied by reduction in the cerebral oxygen extraction fraction and the cerebral metabolic rate of oxygen, i.e., luxury perfusion. Follow-up PET studies showed reduction in cerebral perfusion until it was more closely coupled with oxygen metabolism after the resolution of the acute inflammation. These findings support previous single photon emission computed tomographic data and provide a pathophysiological background for the occurrence of hyperperfusion in HSV encephalitis. This is an interesting example of the luxury perfusion phenomenon occurring in a disease other than cerebral ischemia.

  9. Anterior opercular syndrome induced by Epstein-Barr virus encephalitis.

    PubMed

    Matsushima, Takashi; Nishioka, Kenya; Tanaka, Ryota; Yokoyama, Kazumasa; Hattori, Nobutaka

    2016-01-01

    We report a 19-year-old female presenting with fever, drooling, anarthria, and voluntary facial movement disruption, characteristic of anterior opercular syndrome (AOS). Serological examination revealed Epstein-Barr virus (EBV) infection following acute encephalitis with severe ataxia. A single-photon emission computerized tomography (SPECT) examination indicated hypoperfusion in the left perisylvian region, bilateral thalamus, occipital lobe, and cerebellum. This is the first report of AOS related to EBV encephalitis. SPECT was a useful method for detecting the damaged region of the operculum. In addition, AOS is a clinically distinct entity that may help us understand the mechanisms of language circuits within the operculum.

  10. Herpes simplex encephalitis and subsequent cytomegalovirus encephalitis after chemoradiotherapy for central nervous system lymphoma: a case report and literature review.

    PubMed

    Suzuki, Hiroshi I; Hangaishi, Akira; Hosoya, Noriko; Watanabe, Takuro; Kanda, Yoshinobu; Motokura, Toru; Chiba, Shigeru; Kurokawa, Mineo

    2008-06-01

    Neurological complications during the treatment of hematological malignancies have a wide range of causes. Treatment-related leukoencephalopathy has been recognized as a major complication of combined chemotherapy and radiotherapy for central nervous system (CNS) lymphoma, and can complicate the diagnosis of CNS infection. Herein, we present a patient with diffuse large B-cell lymphoma who developed herpes simplex encephalitis (HSE) and subsequent cytomegalovirus encephalitis after chemoradiotherapy for CNS relapse. Although cerebrospinal fluid examination (CSF) showed no significant pleocytosis, brain magnetic resonance imaging and polymerase chain reaction analysis of the CSF were useful in the diagnosis. With a review of the literature on the association between HSE and radiotherapy for CNS malignancies, our case suggests that an awareness of viral encephalitis is important in the differential diagnosis of acute neurologic disturbance during chemoradiotherapy for CNS lymphoma.

  11. Pregnancy outcome following infections by coxsackie, echo, measles, mumps, hepatitis, polio and encephalitis viruses.

    PubMed

    Ornoy, Asher; Tenenbaum, Alexander

    2006-05-01

    Women may be infected during pregnancy with infectious agents that are often passed unnoticed; however, the causative agent may still traverse the placenta and infect the developing embryo and fetus. Several of these agents (i.e. rubella, cytomegalovirus or Toxoplasma Gondii) may cause severe fetal damage, but most other infections in pregnancy seem to be much less dangerous to the fetus. In this review we discuss the effects of several viral infections during pregnancy where the effects on the developing embryo and fetus are infrequent, but they may sometimes cause severe neonatal disease. The following viruses are discussed: coxsackie and echoviruses, measles and mumps, polioviruses, Japanese and Venezuelan equine encephalitis viruses, West Nile virus and hepatitis viruses A, B, C, D and E. Coxsackie B virus may cause an increase in early spontaneous abortions and rarely, fetal myocarditis; echoviruses do not seem to damage the fetus; measles and mumps may cause increased early and late fetal death and neonatal measles or mumps. The viruses affecting the nervous system may increase early and late spontaneous abortions and, rarely, cause severe damage to the fetal brain. Hepatitis B virus has a high rate of vertical transmission causing fetal and neonatal hepatitis. Hepatitis A, C and E are rarely transmitted trans-placentally; if transmitted, they may cause hepatitis. There is no evidence that immunization in pregnancy against these diseases (with attenuated viruses) may adversely affect pregnancy outcome.

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

    SciTech Connect

    Jaing, C; Gardner, S

    2012-06-05

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

  13. Japanese Temple Geometry

    ERIC Educational Resources Information Center

    Vincent, Jill; Vincent, Claire

    2004-01-01

    Between the 17th and 19th centuries, the Japanese government closed its borders to the outside world in an attempt to become more powerful. Foreign books were banned, people could not travel, and foreigners were not allowed to enter the country. One result of this isolation was the flourishing of sangaku--wooden tablets inscribed with intricately…

  14. Reciprocal Predicates in Japanese.

    ERIC Educational Resources Information Center

    Ishii, Yasuo

    A study of reciprocals in Japanese compares two kinds: (1) a verbal suffix "aw"; and (2) an NP argument "otagai." Although "otagai" appears to be taken care of by syntactic binding theory, it is proposed that there is no evidence for the existence of a syntactic position of the object NP in the case of "aw." The suffix can be characterized as…

  15. Reflexives in Japanese

    ERIC Educational Resources Information Center

    Kishida, Maki

    2011-01-01

    The purpose of this dissertation is to reconsider reflexives in Japanese through the following three steps: (a) separation of genuine reflexive elements from elements that are confounded as reflexives, (b) classification of reflexive anaphors into subtypes based on their semantic difference, and (c) classification of predicates that occur with…

  16. JAPANESE READERS (TITLE SUPPLIED).

    ERIC Educational Resources Information Center

    THREE JAPANESE READERS ARE PRESENTED WHICH CONTAIN VOCABULARY, NOTES, AND DRILL SENTENCES. THE THREE READERS--(1) ARU SARARIIMAN NO ITI-NITI, (2) OTOOSAN WA KAMI-SAMA, AND (3) ARU GAKUSEI NO HANNITI--ARE WRITTEN IN THE ROMAJI ALPHABET. EACH READER HAS A VOCABULARY LISTING WITH ENGLISH EXPLANATIONS AND DRILL SENTENCES. AN ENGLISH WORD DEFINITION…

  17. On Japanese Children's Books.

    ERIC Educational Resources Information Center

    Watanare, Shigeo

    This report, given at a special meeting held in Tehran, presents data and facts concerning yearly publications (books, magazines, and textbooks), translations, and illustrations of Japanese children's literature. The report then discusses at length recent trends in children's literature and library activities for children in the past, present, and…

  18. Reconstruction of Japanese Vowels.

    ERIC Educational Resources Information Center

    Aoki, Haruo

    1972-01-01

    This paper discusses the relationship between linguistic reconstructions and their historical validity using the case of Old Japanese (8th century A.D.) vowels as an example. Reconstructions throughout the paper include only those cases in which the modern reflexes and phonological correspondences between two or more genetically related languages…

  19. Japanese Experiences: "Hentai" Narratives

    ERIC Educational Resources Information Center

    Kama, Amit

    2011-01-01

    For those acquainted with Japanese lesbian, gay, bisexual, and transgender (LGBT) issues, "Queer Voices from Japan" can be good reading. But with only 1 of its 22 chapters informative for researchers, those interested in LGBT youth studies will only indirectly gain insight into a non-Western perspective on youth and sexuality.

  20. Development of human antibody fragments using antibody phage display for the detection and diagnosis of Venezuelan equine encephalitis virus (VEEV)

    PubMed Central

    Kirsch, Martina Inga; Hülseweh, Birgit; Nacke, Christoph; Rülker, Torsten; Schirrmann, Thomas; Marschall, Hans-Jürgen; Hust, Michael; Dübel, Stefan

    2008-01-01

    Background Venezuelan equine encephalitis virus (VEEV) belongs to the Alphavirus group. Several species of this family are also pathogenic to humans and are recognized as potential agents of biological warfare and terrorism. The objective of this work was the generation of recombinant antibodies for the detection of VEEV after a potential bioterrorism assault or an natural outbreak of VEEV. Results In this work, human anti-VEEV single chain Fragments variable (scFv) were isolated for the first time from a human naïve antibody gene library using optimized selection processes. In total eleven different scFvs were identified and their immunological specificity was assessed. The specific detection of the VEEV strains TC83, H12/93 and 230 by the selected antibody fragments was proved. Active as well as formalin inactivated virus particles were recognized by the selected antibody fragments which could be also used for Western blot analysis of VEEV proteins and immunohistochemistry of VEEV infected cells. The anti-VEEV scFv phage clones did not show any cross-reactivity with Alphavirus species of the Western equine encephalitis virus (WEEV) and Eastern equine encephalitis virus (EEEV) antigenic complex, nor did they react with Chikungunya virus (CHIKV), if they were used as detection reagent. Conclusion For the first time, this study describes the selection of antibodies against a human pathogenic virus from a human naïve scFv antibody gene library using complete, active virus particles as antigen. The broad and sensitive applicability of scFv-presenting phage for the immunological detection and diagnosis of Alphavirus species was demonstrated. The selected antibody fragments will improve the fast identification of VEEV in case of a biological warfare or terroristic attack or a natural outbreak. PMID:18764933

  1. Fulminant encephalitis associated with a vaccine strain of rubella virus.

    PubMed

    Gualberto, Felipe Augusto Souza; de Oliveira, Maria Isabel; Alves, Venancio A F; Kanamura, Cristina T; Rosemberg, Sérgio; Sato, Helena Keico; Arantes, Benedito A F; Curti, Suely Pires; Figueiredo, Cristina Adelaide

    2013-12-01

    Involvement of the central nervous system is common in measles, but rare in rubella. However, rubella virus (RV) can cause a variety of central nervous system syndromes, including meningitis, encephalitis, Guillain-Barré syndrome and sub acute sclerosing panencephalitis. We report the occurrence of one fatal case of the encephalitis associated with measles-rubella (MR) vaccine during an immunization campaign in São Paulo, Brazil. A 31 year-old-man, previously in good health, was admitted at emergency room, with confusion, agitation, inability to stand and hold his head up. Ten days prior to admission, he was vaccinated with combined MR vaccine (Serum Institute of India) and three days later he developed 'flu-like' illness with fever, myalgia and headache. Results of clinical and laboratory exams were consistent with a pattern of viral encephalitis. During hospitalization, his condition deteriorated rapidly with tetraplegia and progression to coma. On the 3rd day of hospitalization he died. Histopathology confirmed encephalitis and immunohistochemistry was positive for RV on brain tissue. RV was also detected by qPCR and virus isolation in cerebrospinal fluid, brain and other clinical samples. The sequence obtained from the isolated virus was identical to that of the RA 27/3 vaccine strain.

  2. Scrub Typhus Leading to Acute Encephalitis Syndrome, Assam, India

    PubMed Central

    Bora, Trishna; Laskar, Basanta; Khan, Abdul M.; Dutta, Prafulla

    2017-01-01

    To determine the contribution of Orientia tsutsugamushi, the agent of scrub typhus, as a cause of acute encephalitis syndrome (AES) in Assam, India, we conducted a retrospective study of hospital patients with symptoms of AES during 2013–2015. Our findings suggest that O. tsutsugamushi infection leads to AES and the resulting illness and death. PMID:27875108

  3. Neuropsychiatric Sequelae of Acute Epidemic Encephalitis in Children

    ERIC Educational Resources Information Center

    Ebaugh, Franklin G.

    2007-01-01

    In reviewing the enormous number of articles on all phases of acute epidemic encephalitis one cannot help being impressed by the lack of attention paid to children who have suffered from this disease. This is especially true of the important neuropsychiatric sequelae. During the past few months, seventeen patients have been referred to the…

  4. Current approaches to the treatment of paraneoplastic encephalitis

    PubMed Central

    Grisold, Wolfgang; Giometto, Bruno; Vitaliani, Roberta; Oberndorfer, Stefan

    2011-01-01

    Paraneoplastic neurological syndromes (PNSs) cover a wide range of diseases and involve both the central nervous system (CNS) and peripheral nervous system. Paraneoplastic encephalitis comprises several diseases such as paraneoplastic cerebellar degeneration (PCD), limbic encephalitis (LE), paraneoplastic encephalomyelitis (PEM), brainstem encephalitis, opsomyoclonus syndrome, in addition to other even less frequently occurring entities. LE was the first historically identified CNS PNS, and similarities between other temporal lobe diseases such as herpes encephalitis have been elucidated. In the past few decades several autoantibodies have been described in association with LE. These encompass the classical ‘onconeuronal’ antibodies (abs) such as Hu, Yo, Ri and others, and now additionally abs towards either ion channels or surface antigens. The clinical core findings in LE are various mental changes such as amnesia or confusion, often associated with seizures. Careful characterization of psychiatric manifestations and/or associated neurological signs can help to characterize the syndrome and type of ab. The treatment options in LE depend on the aetiology. In LE caused by onconeuronal abs, the treatment options are poor. In two types of abs associated with LE, abs against ion channels and surface antigens (e.g. NMDA), immunomodulatory treatments seem effective, making these types of LE treatable conditions. However, LE can also occur without being associated with cancer, in which case only immunomodulation is required. Despite effective treatments, some patients’ residual deficits remain, and recurrences have also been described. PMID:21765874

  5. 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

  6. Phylogeographic characterization of tick-borne encephalitis virus from patients, rodents and ticks in Slovenia.

    PubMed

    Fajs, Luka; Durmiši, Emina; Knap, Nataša; Strle, Franc; Avšič-Županc, Tatjana

    2012-01-01

    Tick-borne encephalitis virus (TBEV) is the most important arboviral agent causing infections of the central nervous system in central Europe. Previous studies have shown that TBEV exhibits pronounced genetic variability, which is often correlated to the geographical origin of TBEV. Genetic variability of TBEV has previously been studied predominantly in rodents and ticks, while information about the variability in patients is scarce. In order to understand the molecular relationships of TBEV between natural hosts, vectors and humans, as well as correlation between phylogenetic and geographical clustering, sequences of TBEV E and NS5 protein genes, were obtained by direct sequencing of RT-PCR products from TBE-confirmed patients as well as from rodents and ticks collected from TBE-endemic regions in Slovenia. A total of 27 partial E protein gene sequences representing 15 human, 4 rodent and 8 tick samples and 30 partial NS5 protein gene sequences representing 17 human, 5 rodent and 8 tick samples were obtained. The complete genome sequence of TBEV strain Ljubljana I was simultaneously obtained. Phylogenetic analysis of the E and NS5 protein gene sequences revealed a high degree of TBEV variability in patients, ticks and rodents. Furthermore, an evident correlation between geographical and phylogenetic clustering was shown that was independent of the TBEV host. Moreover, we show the presence of a possible recombination event in the TBEV genome obtained from a patient sample, which was supported with multiple recombination event detection methods. This is the first study that simultaneously analyzed the genetic relationships of directly sequenced TBEV samples from patients, ticks and rodents and provides the largest set of patient-derived TBEV sequences up to date. In addition, we have confirmed the geographical clustering of TBEV sequences in Slovenia and have provided evidence of a possible recombination event in the TBEV genome, obtained from a patient.

  7. Detraditionalisation: Japanese Students in the USA.

    ERIC Educational Resources Information Center

    Ueno, Junko

    2001-01-01

    Focuses on the identity formation of Japanese students temporarily living in the United States. The students were enrolled in Japanese Saturday school and in American public schools. Student interviews reveal a mixture of Japanese and American characteristics. Suggests Japanese students do not reject either culture--Japanese or American--but that…

  8. Vaccinia Virus Recombinants: Expression of VSV Genes and Protective Immunization of Mice and Cattle

    NASA Astrophysics Data System (ADS)

    Mackett, M.; Yilma, T.; Rose, J. K.; Moss, B.

    1985-01-01

    Vesicular stomatitis virus (VSV) causes a contagious disease of horses, cattle, and pigs. When DNA copies of messenger RNA's for the G or N proteins of VSV were linked to a vaccinia virus promoter and inserted into the vaccinia genome, the recombinants retained infectivity and synthesized VSV polypeptides. After intradermal vaccination with live recombinant virus expressing the G protein, mice produced VSV-neutralizing antibodies and were protected against lethal encephalitis upon intravenous challenge with VSV. In cattle, the degree of protection against intradermalingually injected VSV was correlated with the level of neutralizing antibody produced following vaccination.

  9. Improving baculovirus recombination

    PubMed Central

    Zhao, Yuguang; Chapman, David A. G.; Jones, Ian M.

    2003-01-01

    Recombinant baculoviruses have established themselves as a favoured technology for the high-level expression of recombinant proteins. The construction of recombinant viruses, however, is a time consuming step that restricts consideration of the technology for high throughput developments. Here we use a targeted gene knockout technology to inactivate an essential viral gene that lies adjacent to the locus used for recombination. Viral DNA prepared from the knockout fails to initiate an infection unless rescued by recombination with a baculovirus transfer vector. Modified viral DNA allows 100% recombinant virus formation, obviates the need for further virus purification and offers an efficient means of mass parallel recombinant formation. PMID:12527795

  10. CONTRIBUTIONS TO THE PATHOLOGY OF EXPERIMENTAL VIRUS ENCEPHALITIS

    PubMed Central

    Flexner, Simon; Amoss, Harold L.

    1925-01-01

    In this paper is given an account of an inoculable virus disease produced in the rabbit with cerebrospinal fluid taken from a case of vascular and neural syphilis. The study which yielded the results presented was undertaken in the course of an investigation into the etiology of epidemic or lethargic encephalitis. Twenty-seven samples of cerebrospinal fluid, derived from cases of epidemic encephalitis, were tested by us upon rabbits without positive result. The one successful instance in which an inoculable disease was produced arose from the injection of one of three specimens of the cerebrospinal fluid taken from the case of syphilis. Following this success, two subsequent injections of the fluid, taken from the same patient, were made unsuccessfully. Although certain American and European investigators have reported securing a virus from the cerebrospinal fluid of cases of epidemic encephalitis, we have consistently failed in our endeavors to confirm their results. However, we believe that the finding of the J. B. virus may serve to clarify the obscurity and confusion now enveloping the so called virus of encephalitis. It had previously been shown that no biological differences could be detected between the herpes and the encephalitis strains of virus. The former, as is well known, is readily secured by inoculating rabbits with the contents of herpes vesicles, while the latter has, at best, been obtained with great difficulty. The J. B. virus agrees biologically with the herpes and encephalitis strains of virus. It is our opinion that the J. B. virus is merely a herpes virus which has gained access to the cerebrospinal fluid and, at the time of inoculation of the rabbits, was present in a concentration sufficing to induce virus encephalitis. The fact, if fact it is proved to be, that the herpes virus may find its way into the cerebrospinal fluid opens to question all the supposed instances of successful implantation of a virus of epidemic encephalitis upon the

  11. Directory of Japanese researchers available

    NASA Astrophysics Data System (ADS)

    The National Center for Science Information System Japanese Scientific and Engineering Database Access Project, sponsored by the National Science Foundation and Japan's NACSIS, has added four new databases to its free service, bringing the total number of available databases to 13.The new Directory of Japanese Researchers covers researchers affiliated with Japanese universities and academic research centers. Each researcher is listed by name, date of birth, organizational affiliation, education and degrees, memberships and awards, areas of specialization, and representative publications. Non-Japanese researchers are also covered.

  12. Anti-NMDA Receptor Encephalitis in the Polar Bear (Ursus maritimus) Knut.

    PubMed

    Prüss, H; Leubner, J; Wenke, N K; Czirják, G Á; Szentiks, C A; Greenwood, A D

    2015-08-27

    Knut the polar bear of the Berlin Zoological Garden drowned in 2011 following seizures and was diagnosed as having suffered encephalitis of unknown etiology after exhaustive pathogen screening. Using the diagnostic criteria applied to human patients, we demonstrate that Knut's encephalitis is almost identical to anti-NMDA receptor encephalitis which is a severe autoimmune disease representing the most common non-infectious encephalitis in humans. High concentrations of antibodies specific against the NR1 subunit of the NMDA receptor were detected in Knut's cerebrospinal fluid. Histological examination demonstrated very similar patterns of plasma cell infiltration and minimal neuronal loss in affected brain areas. We conclude that Knut suffered anti-NMDA receptor encephalitis making his the first reported non-human case of this treatable disease. The results suggest that anti-NMDA receptor encephalitis may be a disease of broad relevance to mammals that until now has remained undiagnosed.

  13. Anti-NMDA Receptor Encephalitis in the Polar Bear (Ursus maritimus) Knut

    PubMed Central

    Prüss, H.; Leubner, J.; Wenke, N. K.; Czirják, G. Á.; Szentiks, C. A.; Greenwood, A. D.

    2015-01-01

    Knut the polar bear of the Berlin Zoological Garden drowned in 2011 following seizures and was diagnosed as having suffered encephalitis of unknown etiology after exhaustive pathogen screening. Using the diagnostic criteria applied to human patients, we demonstrate that Knut’s encephalitis is almost identical to anti-NMDA receptor encephalitis which is a severe autoimmune disease representing the most common non-infectious encephalitis in humans. High concentrations of antibodies specific against the NR1 subunit of the NMDA receptor were detected in Knut’s cerebrospinal fluid. Histological examination demonstrated very similar patterns of plasma cell infiltration and minimal neuronal loss in affected brain areas. We conclude that Knut suffered anti-NMDA receptor encephalitis making his the first reported non-human case of this treatable disease. The results suggest that anti-NMDA receptor encephalitis may be a disease of broad relevance to mammals that until now has remained undiagnosed. PMID:26313569

  14. Cognitive inferences in fossil apes (Primates, Hominoidea): does encephalization reflect intelligence?

    PubMed

    Alba, David M

    2010-01-01

    Paleobiological inferences on general cognitive abilities (intelligence) in fossil hominoids strongly rely on relative brain size or encephalization, computed by means of allometric residuals, quotients or constants. Th is has been criticized on the basis that it presumably fails to reflect the higher intelligence of great apes, and absolute brain size has been favored instead. Many problems of encephalization metrics stem from the decrease of allometric slopes towards lower taxonomic level, thus making it difficult to determine at what level encephalization metrics have biological meaning. Here, the hypothesis that encephalization can be used as a good neuroanatomical proxy for intelligence is tested at two different taxonomic levels. A significant correlation is found between intelligence and encephalization only at a lower taxonomic level, i.e. on the basis of a low allometric slope, irrespective of whether species data or independent contrasts are employed. This indicates that higher-level slopes, resulting from encephalization grade shifts between subgroups (including hylobatids vs. great apes), do not reflect functional equivalence, whereas lower-level metrics can be employed as a paleobiological proxy for intelligence. Thus, in accordance to intelligence rankings, lower-level metrics indicate that great apes are more encephalized than both monkeys and hylobatids. Regarding fossil taxa, encephalization increased during hominin evolution (particularly in Homo), but during the Miocene a significant shift towards higher encephalization (and inferred enhanced cognitive abilities) must have been also involved in the emergence of the great-ape-and-human clade (Hominidae). This is confirmed by the modern great-ape-like degree of encephalization displayed by the fossil great ape Hispanopithecus, which contrasts with the rather hylobatid-like degree of the stem hominoid Proconsul. The similarly low encephalization of Oreopithecus might result from secondary reduction

  15. Molecular Strategy for the Construction of a Genetically Engineered Vaccine for Venezuelan Equine Encephalitis Virus

    DTIC Science & Technology

    1991-03-29

    AD-A236 920 MOLECULAR STRATEGY FOR THE CONSTRUCTION OF A GENETICALLY ENGINEERED VACCINE FOR VENEZUELAN EQUINE ENCEPHALITIS VIRUS FINAL REPORT ROBERT...89-C-9089 engineered vaccine for Venezuelan Equine Encephalitis Virus 62787A 3M162787A871 AD Robert Edward Johnston WUDA318408 Nancy Lee Davis...multiple mutants were more attenuated than those containing a single attenuating Venezuelan equine encephalitis virus (VEE) full-length clones; In vitro

  16. Gene Knockdown of Venezuelan Equine Encephalitis Virus E2 Glycoprotein Using DNA-Directed RNA Interference

    DTIC Science & Technology

    2006-12-01

    e _s~u~m mary - Introduction: Alphaviruses are a large family of RNA viruses that can cause acute infection resulting in arthritis and encephalitis...One of the important alphaviruses is the Venezuelan equine encephalitis virus. This virus has been linked to a number of outbreaks in both North and... replication of VEE virus in vitro. Bhogal, H.S., McLaws, L.J., and Jager, S.J. 2006. Gene Knockdown of Venezuelan Equine Encephalitis Virus E2

  17. Toxoplasmic encephalitis associated with meningitis in a heart transplant recipient.

    PubMed

    Baliu, C; Sanclemente, G; Cardona, M; Castel, M A; Perez-Villa, F; Moreno, A; Cervera, C

    2014-08-01

    Toxoplasma gondii is an opportunistic pathogen that causes neurologic and extraneurologic manifestations in immunosuppressed patients. Encephalitis and intracranial mass lesions are easily recognized as typical manifestations of toxoplasmosis. However, meningitis caused by T. gondii is a rare condition with very few cases described in the literature. We present the case of a heart transplant recipient who developed toxoplasmic encephalitis associated with meningitis. After an extensive review of the medical literature, we found only 1 case of meningitis in solid organ transplant recipients and <25 cases in immunosuppressed patients, such as patients infected with human immunodeficiency virus or those with Hodgkin's disease. In this report, we consider toxoplasmosis in the differential diagnosis of meningitis in immunocompromised individuals.

  18. Gerstmann's syndrome following an acute herpes simplex encephalitis.

    PubMed

    Ilchevsky, S; Boev, I; Kazakova, T

    1998-01-01

    The authors present a rare clinical case of a woman who developed Gerstmann's syndrome following an acute Herpes simplex viral encephalitis. Clinical observation and laboratory evaluation were performed during the acute phase of the disease. After that the follow-up continued for one-year period. The localization of the pathologic process was determined by computerized tomography, conducted periodically. The characteristics of the clinical picture are interpreted in the context of the contemporary concepts of the topical diagnosis of Gerstmann's syndrome. The possibility of a sudden onset of acute Herpes simplex viral encephalitis without a preceding febrile-intoxication syndrome is worth noting. Conclusions are drawn stressing the need of an early etiologic treatment and the importance of the rehabilitation activities during the convalescence period.

  19. [Autoimmune encephalitis induced by antibodies against GABA-A receptor].

    PubMed

    González R, Pablo; Hudson A, Lorena; Basáez M, Esteban; Miranda C, Marcelo

    2016-11-01

    Among autoimmune encephalitides, a prevalent group are those associated with antibodies against the N-Methyl-D-aspartate receptor, which present with behavior abnormalities, psychosis, seizures and abnormal movements. A new variant, mediated by antibodies against the GABA-A receptor, was recen-tly described. We report a 66-years-old female with this form of encephalitis whose main manifestation was the presence of severe seizures leading to status epilepticus. The patient had a good response to immunomodulatory therapy with intravenous methylprednisolone, azathioprine and anticonvulsants. The laboratory tests initially detected anti-thyroid peroxidase antibodies which lead to the misdiagnosis of Hashimoto Encephalitis, which was ruled out after the detection of antibodies against GABA-A receptor. No malignancy was detected.

  20. Management of granulomatous amebic encephalitis: Laboratory diagnosis and treatment

    PubMed Central

    Parija, Subhash Chandra; Dinoop, KP; Venugopal, Hrudya

    2015-01-01

    Granulomatous amebic encephalitis is a life-threatening central nervous system (CNS) infection caused by the free-living amoebae Acanthamoeba spp., Balamuthia mandrillaris and Sappinia pedata. The disease has a subacute to chronic onset affecting commonly the immunocompromised population with high mortality rate. The diagnosis of this disease entity requires high suspicion with appropriate sample collection and testing by the laboratory experts. Radiological investigations are nonspecific and commonly confused with CNS tuberculosis, neurocysticercosis, disseminated encephalomyelitis, viral encephalitis etc., delaying the accurate diagnosis of these cases. Early diagnosis plays a crucial role in the survival of these cases since appropriate management can be initiated. No single drug is effective; hence multiple antibiotics targeting various proteins or receptors are required for successful treatment. A combination of surgical and medical interventions involving multiple specialty experts is required to prevent death and morbidity in survivors. PMID:25709949

  1. Encephalization quotients and life-history traits in the Sirenia

    USGS Publications Warehouse

    O'Shea, T.J.; Reep, R.L.

    1990-01-01

    Relative brain size in the Sirenia is unusually small. Encephalization quotients are 0.27 for Florida manatees (Trichechus manatus) and 0.38 for dugongs (Dugong dugon). Estimates for Steller's sea cow (Hydrodamalis gigas) range from 0.12 to 0.19. These values are among the lowest known for Recent mammals, and seemingly have changed little since the Eocene. A body plan specialized for the aquatic environment does not account for low encephalization quotients; values are substantially less than predicted based on cetacean or pinniped allometry. Life-history, ecological, and behavioral traits of the Sirenia are typical of relatively large-brained species. Low quality food and a low metabolic rate, however, are characteristic of the Sirenia and other small-brained mammals. Acting through prolonged postnatal growth, selection also likely favored large body size in the Sirenia without a correlated increase in brain size.

  2. Efficacies of treatments for anti-NMDA receptor encephalitis.

    PubMed

    Wang, Hsiuying

    2016-01-01

    Treatments for anti-N-methyl-D-aspartate (NMDA) receptor encephalitis include immunotherapy with steroids, intravenous immunoglobulin, plasma exchange, or plasmapheresis as first-line treatments, immunotherapy with rituximab or cyclophosphamide as second-line treatments, and tumor removal. In this systematic review, we evaluated previous studies and examined the association between certain microRNAs and anti-NMDA receptor encephalitis to investigate the performance of different treatment combinations. The efficacies of different combinations of treatments classified into the following four categories were compared: (I) intravenous immunoglobulin administration, (II) plasmapheresis or plasma exchange, (III) treatment with rituximab or cyclophosphamide and (IV) tumor removal. Statistical analyses showed that treatment combinations including at least two of these categories resulted in higher efficacy rates than treatment with a single form of therapy. These findings suggest that if a patient is not recovering, converting to other therapies is more likely to result in early recovery than continuing on the original therapy.

  3. Molecular mechanisms of neuroinflammation and injury during acute viral encephalitis.

    PubMed

    Shives, Katherine D; Tyler, Kenneth L; Beckham, J David

    2017-03-11

    Viral infections in the central nervous system are a major cause of encephalitis. West Nile virus (WNV) and Herpes simplex virus (HSV) are the most common causes of viral encephalitis in the United States. We review the role of neuroinflammation in the pathogenesis of WNV and HSV infections in the central nervous system (CNS). We discuss the role of the innate and cell-mediated immune responses in peripheral control of viral infection, viral invasion of the CNS, and in inflammatory-mediated neuronal injury. By understanding the role of specific inflammatory responses to viral infections in the CNS, targeted therapeutic approaches can be developed to maximize control of acute viral infection while minimizing neuronal injury in the CNS.

  4. Post Tick-Borne Encephalitis Virus Vaccination Narcolepsy with Cataplexy

    PubMed Central

    Hidalgo, Hildegard; Kallweit, Ulf; Mathis, Johannes; Bassetti, Claudio L.

    2016-01-01

    Study Objectives: Narcolepsy with cataplexy (NC) is a chronic neurological disorder thought to result from an altered immune response based on a genetic predisposition coupled with environmental factors. Pandemrix vaccination has been reported to increase the risk of narcolepsy. We aimed at identifying other vaccines associated with the onset of narcolepsy. Methods: Case series and retrospective database study. Results: We identified four cases of NC following a tick-borne encephalitis (TBE) vaccination with FSME Immun. Additional four cases could be detected in the database of the Paul-Ehrlich-Institut, Federal Institute for Vaccines and Biomedicines in Germany. Conclusions: Our findings implicate TBE vaccination as a potential additional environmental factor for the development of NC and add additional evidence for an immunological mechanism in the pathogenesis of the disease. Citation: Hidalgo H, Kallweit U, Mathis J, Bassetti CL. Post tick-borne encephalitis virus vaccination narcolepsy with cataplexy. SLEEP 2016;39(10):1811–1814. PMID:27397572

  5. Fatal West Nile virus encephalitis in a renal transplant recipient.

    PubMed

    Cushing, Melissa M; Brat, Daniel J; Mosunjac, Mario I; Hennigar, Randolph A; Jernigan, Daniel B; Lanciotti, Robert; Petersen, Lyle R; Goldsmith, Cynthia; Rollin, Pierre E; Shieh, Wun-Ju; Guarner, Jeannette; Zaki, Sherif R

    2004-01-01

    West Nile virus (WNV), a mosquito-transmitted single-stranded RNA flavivirus, causes human disease of variable severity. We report clinical and pathologic findings of fatal encephalitis from the transmission of WNV from an organ donor to a kidney transplant recipient. The patient developed a febrile illness 18 days after transplantation, which progressed to encephalitis. Postmortem examination demonstrated extensive viral encephalopathic changes. Immunohistochemical studies highlighted WNV antigens within neurons, especially in the cerebellum and brainstem. Flavivirus virions were detected ultrastructurally within the cerebellum, and WNV was isolated from the brain and the brainstem. Thus, this case demonstrates the first death in the first solid organ transplant-associated transmission of WNV. Immunosuppression of the transplant recipient might have been responsible for the fulminant viral effects. The pathologic diagnosis helped guide subsequent epidemiologic and laboratory studies.

  6. Diagnostic Pathways as Social and Participatory Practices: The Case of Herpes Simplex Encephalitis

    PubMed Central

    Cooper, Jessie; Kierans, Ciara; Defres, Sylviane; Easton, Ava; Kneen, Rachel; Solomon, Tom

    2016-01-01

    Herpes simplex virus (HSV) encephalitis is a potentially devastating disease, with significant rates of mortality and co-morbidities. Although the prognosis for people with HSV encephalitis can be improved by prompt treatment with aciclovir, there are often delays involved in the diagnosis and treatment of the disease. In response, National Clinical Guidelines have been produced for the UK which make recommendations for improving the management of suspected viral encephalitis. However, little is currently known about the everyday experiences and processes involved in the diagnosis and care of HSV encephalitis. The reported study aimed to provide an account of the diagnosis and treatment of HSV encephalitis from the perspective of people who had been affected by the condition. Thirty narrative interviews were conducted with people who had been diagnosed with HSV encephalitis and their significant others. The narrative accounts reveal problems with gaining access to a diagnosis of encephalitis and shortfalls in care for the condition once in hospital. In response, individuals and their families work hard to obtain medical recognition for the problem and shape the processes of acute care. As a consequence, we argue that the diagnosis and management of HSV encephalitis needs to be considered as a participatory process, which is co-produced by health professionals, patients, and their families. The paper concludes by making recommendations for developing the current management guidelines by formalising the critical role of patients and their significant others in the identification, and treatment of, HSV encephalitis. PMID:26960197

  7. Antecedent anti-NMDA receptor encephalitis in two patients with multiple sclerosis.

    PubMed

    Baheerathan, A; Brownlee, W J; Chard, D T; Shields, K; Gregory, R; Trip, S A

    2017-02-01

    Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune disorder characterised by psychiatric symptoms, movement disorder and seizures often evolving into a severe encephalopathy. An overlap has recently been recognised between anti-NMDAR encephalitis and inflammatory demyelinating disorders, particularly neuromyelitis optical spectrum disorder (NMOSD). In this case report, we describe two patients with an initial presentation consistent with anti-NMDAR encephalitis who have subsequently developed relapsing-remitting multiple sclerosis (MS) and discuss the literature pertaining to potential overlap between NMDAR encephalitis and inflammatory demyelinating disorders.

  8. Unusual Clinical Presentation and Role of Decompressive Craniectomy in Herpes Simplex Encephalitis.

    PubMed

    Singhi, Pratibha; Saini, Arushi Gahlot; Sahu, Jitendra Kumar; Kumar, Nuthan; Vyas, Sameer; Vasishta, Rakesh Kumar; Aggarwal, Ashish

    2015-08-01

    Decompressive craniectomy in pediatric central nervous infections with refractory intracranial hypertension is less commonly practiced. We describe improved outcome of decompressive craniectomy in a 7-year-old boy with severe herpes simplex encephalitis and medically refractory intracranial hypertension, along with a brief review of the literature. Timely recognition of refractory intracranial hypertension and surgical decompression in children with herpes simplex encephalitis can be life-saving. Additionally, strokelike atypical presentations are being increasingly recognized in children with herpes simplex encephalitis and should not take one away from the underlying herpes simplex encephalitis.

  9. Electroconvulsive therapy and/or plasmapheresis in autoimmune encephalitis?

    PubMed Central

    Gough, Jessica L; Coebergh, Jan; Chandra, Brunda; Nilforooshan, Ramin

    2016-01-01

    Autoimmune encephalitis is a poorly understood condition that can present with a combination of neurological and psychiatric symptoms, either of which may predominate. There are many autoantibodies associated with a variety of clinical syndromes - anti-N-Methyl-D-Aspartate receptor (NMDAR) is the commonest. Currently, the most widely used therapy is prompt plasmapheresis and steroid treatment (and tumour resection if indicated), followed by second line immunosuppression if this fails. Given the growing awareness of autoimmune encephalitis as an entity, it is increasingly important that we consider it as a potential diagnosis in order to provide timely, effective treatment. We discuss several previously published case reports and one new case. These reports examined the effects of electroconvulsive therapy (ECT) on patients with autoimmune encephalitis, particularly those in whom psychiatric symptoms are especially debilitating and refractory to standard treatment. We also discuss factors predicting good outcome and possible mechanisms by which ECT may be effective. Numerous cases, such as those presented by Wingfield, Tsutsui, Florance, Sansing, Braakman and Matsumoto, demonstrate effective use of ECT in anti-NMDAR encephalitis patients with severe psychiatric symptoms such as catatonia, psychosis, narcolepsy and stupor who had failed to respond to standard treatments alone. We also present a new case of a 71-year-old female who presented to a psychiatric unit initially with depression, which escalated to catatonia, delusions, nihilism and auditory hallucinations. After anti-NMDAR antibodies were isolated, she was treated by the neurology team with plasmapheresis and steroids, with a partial response. She received multiple sessions of ECT and her psychiatric symptoms completely resolved and she returned to her premorbid state. For this reason, we suggest that ECT should be considered, particularly in those patients who are non-responders to standard therapies. PMID

  10. MRI findings in eastern equine encephalitis: the "parenthesis" sign.

    PubMed

    Nickerson, Joshua P; Kannabiran, Suma; Burbank, Heather N

    2016-01-01

    Two patients with eastern equine encephalitis (EEE) presented to a tertiary referral center. Both subjects' brain magnetic resonance imaging showed T2/FLAIR (fluid-attenuated inversion recovery) hyperintensities including linear areas of hyperintensity in the external and internal capsules with sparing of the lentiform nuclei. Single case reports of imaging findings in EEE exist with nonspecific patterns of abnormality. We propose that this "( ) parentheses sign" on T2 or FLAIR imaging may distinguish EEE from other processes.

  11. Relapsing herpes simplex encephalitis resulting in Kluver-Bucy syndrome.

    PubMed

    Ku, Bon D; Yoon, Sung Sang

    2011-01-01

    Relapsing herpes simplex encephalitis (HSE) rarely occurs after acyclovir treatment. We treated a patient with relapsing HSE of the contralateral temporal lobe, resulting in Klüver-Bucy syndrome, after a full-dose acyclovir treatment. This case suggests that physicians should consider sudden behavioral and emotional changes after HSE treatment as a possible indication of relapsing HSE, as well as possible temporal lobe epilepsy, and the need to administer longer acyclovir treatment for select patients.

  12. Cyst rupture as a pathogenic mechanism of toxoplasmic encephalitis.

    PubMed

    Frenkel, J K; Escajadillo, A

    1987-05-01

    Seemingly intact cysts and sequential stages of disintegrating cysts of Toxoplasma were identified immunohistologically within developing microglial nodules in a Panamanian night monkey (Aotus lemurinus). This monkey had been successfully immunized and challenged 5 months earlier. This supports the hypothesis that glial nodules unassociated with Toxoplasma tachyzoites may represent the tombstone of a Toxoplasma cyst. Disintegration of cysts may give rise to clinical encephalitis in the presence of apparently adequate immunity.

  13. Susceptibility of two turtle species to eastern equine encephalitis virus.

    PubMed

    Smith, A L; Anderson, C R

    1980-10-01

    Two species of turtle collected in southern New England were inoculated subcutaneously with eastern equine encephalitis virus. The spotted turtles (Clemmys guttata) developed viremia and neutralizing antibody after exposure to 3 logs or more of virus. Viremia was not detected in the eastern painted turtles (Chrysemys picta), and neutralizing antibody was detected in only 1 of 15 inoculated C. picta; however, since pre-inoculation serum was not obtained from this animal, the possibility of natural infection cannot be eliminated.

  14. Transcranial direct current stimulation in adolescent and adult Rasmussen's encephalitis.

    PubMed

    San-Juan, Daniel; Calcáneo, Juan de Dios Del Castillo; González-Aragón, Maricarmen Fernández; Bermúdez Maldonado, Luis; Avellán, Alvaro Moreno; Argumosa, Edgar Valentín Gómez; Fregni, Felipe

    2011-01-01

    Rasmussen's encephalitis is a rare, progressive inflammatory disease that typically affects one cerebral hemisphere and causes intractable partial-onset seizures. Currently, the only effective therapy is hemispherectomy; however, this procedure is associated with irreversible neurological deficits. Novel therapeutic approaches to this condition are therefore necessary. One possible option that has not yet been extensively studied is electrical cathodal transcranial direct current stimulation (cTDCS). We describe the cases of two patients with atypical-onset Rasmussen's encephalitis who underwent cTDCS at 1- and 2-mA intensity for 60 minutes in four sessions (on days 0, 7, 30, and 60). No complications were recorded during their therapy. At follow-up evaluations 6 and 12 months later, one patient had a significant reduction in seizure frequency and one was seizure free. Additionally, both patients had improved levels of alertness and language. This is the first time that cTDCS has been applied in serial sessions to treat Rasmussen's encephalitis to avoid or delay surgical treatment.

  15. A New Model for Hendra Virus Encephalitis in the Mouse

    PubMed Central

    Dups, Johanna; Middleton, Deborah; Yamada, Manabu; Monaghan, Paul; Long, Fenella; Robinson, Rachel; Marsh, Glenn A.; Wang, Lin-Fa

    2012-01-01

    Hendra virus (HeV) infection in humans is characterized by an influenza like illness, which may progress to pneumonia or encephalitis and lead to death. The pathogenesis of HeV infection is poorly understood, and the lack of a mouse model has limited the opportunities for pathogenetic research. In this project we reassessed the role of mice as an animal model for HeV infection and found that mice are susceptible to HeV infection after intranasal exposure, with aged mice reliably developing encephalitic disease. We propose an anterograde route of neuroinvasion to the brain, possibly along olfactory nerves. This is supported by evidence for the development of encephalitis in the absence of viremia and the sequential distribution of viral antigen along pathways of olfaction in the brain of intranasally challenged animals. In our studies mice developed transient lower respiratory tract infection without progressing to viremia and systemic vasculitis that is common to other animal models. These studies report a new animal model of HeV encephalitis that will allow more detailed studies of the neuropathogenesis of HeV infection, particularly the mode of viral spread and possible sequestration within the central nervous system; investigation of mechanisms that moderate the development of viremia and systemic disease; and inform the development of improved treatment options for human patients. PMID:22808132

  16. Catatonic Syndrome in Anti-NMDA Receptor Encephalitis.

    PubMed

    Mythri, Starlin Vijay; Mathew, Vivek

    2016-01-01

    Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is a newly recognised autoimmune condition. With its typical clinical pattern, consistent association with the presence of auto antibodies and rapid improvement with immunotherapy, this condition is giving insights into the boundaries between psychiatry and other neurosciences, and is opening avenues for future research. In a young lady who presented with catatonia, we considered anti-NMDA receptor encephalitis, after ruling out other aetiologies. After a positive antibody test we treated her with immunotherapy. She showed gradual improvement in her psychotic and catatonic symptoms. Knowledge regarding the nature and function of NMDA receptors and pathophysiology of this particular encephalitis is important for psychiatric practice. The great opportunity for research in this area due to its association with psychotic disorders is evident but an appeal to temper the enthusiasm by considering the historical lessons learnt from Karl Jaspers' critique of General Paresis of Insane, is in place. Catatonic syndrome has to be conceptualised broadly and should be recognised with a separate nosological position.

  17. [Anti-NMDA Receptor Antibody-Related Encephalitis].

    PubMed

    Nagayama, Shigemi; Tanaka, Keiko

    2016-09-01

    Recently, the search for diagnostic antibody markers has drawn considerable attention in relation to autoimmune encephalitis. Among the antibody markers, the most frequently detected is the anti-N-methyl-D-aspartate receptor (NMDAR)antibody. Patients with this antibody develop characteristic clinical features. This disease tends to affect young women, and starts with psychiatric symptoms followed by seizures, involuntary movements, autonomic failure, and respiratory failure. Nearly half of these female patients have ovarian teratoma. Some of the patients with anti-NMDAR antibody show atypical clinical features. Approximately 4% show only psychiatric symptoms, which might lead to a diagnosis of malignant catatonia. Other reports describe patients experiencing refractory seizures to have the anti-NMDAR antibody. Some of the antibody-positive patients are associated with demyelinating disorders, and some develop anti-NMDAR encephalitis after recovery from herpes simplex encephalitis. It is important to test the anti-NMDAR antibody in these groups since immunotherapy ameliorates their symptoms. The anti-NMDAR antibody binds to the constitutional epitope at the extracellular domain of GluN1 and disrupts its function. Early introduction of immunotherapy together with tumor resection will results in improvement of neurological symptoms.

  18. Catatonic Syndrome in Anti-NMDA Receptor Encephalitis

    PubMed Central

    Mythri, Starlin Vijay; Mathew, Vivek

    2016-01-01

    Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is a newly recognised autoimmune condition. With its typical clinical pattern, consistent association with the presence of auto antibodies and rapid improvement with immunotherapy, this condition is giving insights into the boundaries between psychiatry and other neurosciences, and is opening avenues for future research. In a young lady who presented with catatonia, we considered anti-NMDA receptor encephalitis, after ruling out other aetiologies. After a positive antibody test we treated her with immunotherapy. She showed gradual improvement in her psychotic and catatonic symptoms. Knowledge regarding the nature and function of NMDA receptors and pathophysiology of this particular encephalitis is important for psychiatric practice. The great opportunity for research in this area due to its association with psychotic disorders is evident but an appeal to temper the enthusiasm by considering the historical lessons learnt from Karl Jaspers’ critique of General Paresis of Insane, is in place. Catatonic syndrome has to be conceptualised broadly and should be recognised with a separate nosological position. PMID:27114630

  19. Issei: Japanese Immigrants in Hawaii.

    ERIC Educational Resources Information Center

    Kimura, Yukiko

    Coming to Hawaii before July 1, 1924, when the Japanese Exclusion Act became effective, the experiences of the Issei or first generation are described. Divided into four parts, this book examines the experiences of Japanese immigrants in Hawaii from 1885 through 1970. Part 1, "The Formation and Stabilization of the Issei Community,"…

  20. Developmental Sentence Scoring for Japanese

    ERIC Educational Resources Information Center

    Miyata, Susanne; MacWhinney, Brian; Otomo, Kiyoshi; Sirai, Hidetosi; Oshima-Takane, Yuriko; Hirakawa, Makiko; Shirai, Yasuhiro; Sugiura, Masatoshi; Itoh, Keiko

    2013-01-01

    This article reports on the development and use of the Developmental Sentence Scoring for Japanese (DSSJ), a new morpho-syntactical measure for Japanese constructed after the model of Lee's English Developmental Sentence Scoring model. Using this measure, the authors calculated DSSJ scores for 84 children divided into six age groups between 2;8…

  1. Asian Pacific Perspectives: Japanese Americans.

    ERIC Educational Resources Information Center

    Los Angeles Unified School District, CA.

    These instructional materials on Japanese Americans for elementary students were developed through the K.E.Y.S. project (Knowledge of English Yields Success). Information is included on early immigrants, their historical and cultural background, and current problems of Japanese Americans. Resource guides describe the purpose of the unit, how to…

  2. The modern Japanese color lexicon.

    PubMed

    Kuriki, Ichiro; Lange, Ryan; Muto, Yumiko; Brown, Angela M; Fukuda, Kazuho; Tokunaga, Rumi; Lindsey, Delwin T; Uchikawa, Keiji; Shioiri, Satoshi

    2017-03-01

    Despite numerous prior studies, important questions about the Japanese color lexicon persist, particularly about the number of Japanese basic color terms and their deployment across color space. Here, 57 native Japanese speakers provided monolexemic terms for 320 chromatic and 10 achromatic Munsell color samples. Through k-means cluster analysis we revealed 16 statistically distinct Japanese chromatic categories. These included eight chromatic basic color terms (aka/red, ki/yellow, midori/green, ao/blue, pink, orange, cha/brown, and murasaki/purple) plus eight additional terms: mizu ("water")/light blue, hada ("skin tone")/peach, kon ("indigo")/dark blue, matcha ("green tea")/yellow-green, enji/maroon, oudo ("sand or mud")/mustard, yamabuki ("globeflower")/gold, and cream. Of these additional terms, mizu was used by 98% of informants, and emerged as a strong candidate for a 12th Japanese basic color term. Japanese and American English color-naming systems were broadly similar, except for color categories in one language (mizu, kon, teal, lavender, magenta, lime) that had no equivalent in the other. Our analysis revealed two statistically distinct Japanese motifs (or color-naming systems), which differed mainly in the extension of mizu across our color palette. Comparison of the present data with an earlier study by Uchikawa & Boynton (1987) suggests that some changes in the Japanese color lexicon have occurred over the last 30 years.

  3. Counseling Japanese Men on Fathering

    ERIC Educational Resources Information Center

    Seto, Atsuko; Becker, Kent W.; Akutsu, Motoko

    2006-01-01

    The authors review an article (J. Yamamoto & F. Tagami, 2004) published in the "Japanese Journal of Counseling Science" that described changes in contemporary Japanese family structures and illustrated a therapy process with a father to enhance the father-son relationship. Implications for the counseling profession in working with…

  4. Mutation analysis of the fusion domain region of St. Louis encephalitis virus envelope protein

    SciTech Connect

    Trainor, Nicole B.; Crill, Wayne D. . E-mail: wcrill@cdc.gov; Roberson, Jill A.; Chang, Gwong-Jen J.

    2007-04-10

    The immune response to flavivirus infections produces both species-specific and flavivirus cross-reactive antibodies. The presence of cross-reactive antibodies complicates serodiagnosis of flavivirus infections, especially secondary infections caused by a heterologous virus. A successful public health response to the growing global threat posed by flaviviruses necessitates the development of virus-specific diagnostic antigens. The flavivirus envelope (E) glycoprotein is the principle antigen stimulating protective immunity during infection. Using recombinant St. Louis encephalitis virus-like particles (VLPs), we have identified amino acid residues involved in flavivirus cross-reactive epitope determinants. Most significant among the residues studied are three highly conserved amino acids in the fusion peptide: Gly104, Gly106, and Leu107. Substitutions of these residues dramatically influenced VLP secretion and cross-reactive monoclonal antibody reactivity. These results provide critical insight into the antigenic structure of the flaviviral E protein and toward development of species-specific diagnostic antigens that should improve both flavivirus diagnosis and estimates of disease burden.

  5. Protection against Fatal Sindbis Virus Encephalitis by Beclin, a Novel Bcl-2-Interacting Protein

    PubMed Central

    Liang, Xiao Huan; Kleeman, Linda K.; Jiang, Hui Hui; Gordon, Gerald; Goldman, James E.; Berry, Gail; Herman, Brian; Levine, Beth

    1998-01-01

    bcl-2, the prototypic cellular antiapoptotic gene, decreases Sindbis virus replication and Sindbis virus-induced apoptosis in mouse brains, resulting in protection against lethal encephalitis. To investigate potential mechanisms by which Bcl-2 protects against central nervous system Sindbis virus infection, we performed a yeast two-hybrid screen to identify Bcl-2-interacting gene products in an adult mouse brain library. We identified a novel 60-kDa coiled-coil protein, Beclin, which we confirmed interacts with Bcl-2 in mammalian cells, using fluorescence resonance energy transfer microscopy. To examine the role of Beclin in Sindbis virus pathogenesis, we constructed recombinant Sindbis virus chimeras that express full-length human Beclin (SIN/beclin), Beclin lacking the putative Bcl-2-binding domain (SIN/beclinΔBcl-2BD), or Beclin containing a premature stop codon near the 5′ terminus (SIN/beclinstop). The survival of mice infected with SIN/beclin was significantly higher (71%) than the survival of mice infected with SIN/beclinΔBcl-2BD (9%) or SIN/beclinstop (7%) (P < 0.001). The brains of mice infected with SIN/beclin had fewer Sindbis virus RNA-positive cells, fewer apoptotic cells, and lower viral titers than the brains of mice infected with SIN/beclinΔBcl-2BD or SIN/beclinstop. These findings demonstrate that Beclin is a novel Bcl-2-interacting cellular protein that may play a role in antiviral host defense. PMID:9765397

  6. TLR9-Targeted Biodegradable Nanoparticles as Immunization Vectors Protect against West Nile Encephalitis

    PubMed Central

    Demento, Stacey L.; Bonafé, Nathalie; Cui, Weiguo; Kaech, Susan M.; Caplan, Michael J.; Fikrig, Erol; Ledizet, Michel; Fahmy, Tarek M.

    2013-01-01

    Vaccines that activate humoral and cell-mediated immune responses are urgently needed for many infectious agents, including the flaviviruses dengue and West Nile (WN) virus. Vaccine development would be greatly facilitated by a new approach, in which nanoscale modules (Ag, adjuvant, and carrier) are assembled into units that are optimized for stimulating immune responses to a specific pathogen. Toward that goal, we formulated biodegradable nanoparticles loaded with Ag and surface modified with the pathogen-associated molecular pattern CpG oligodeoxynucleotides. We chose to evaluate our construct using a recombinant envelope protein Ag from the WN virus and tested the efficiency of this system in eliciting humoral and cellular responses and providing protection against the live virus. Animals immunized with this system showed robust humoral responses polarized toward Th1 immune responses compared with predominately Th2-biased responses with the adjuvant aluminum hydroxide. Immunization with CpG oligodeoxynucleotide-modified nanoparticles resulted in a greater number of circulating effector T cells and greater activity of Ag-specific lymphocytes than unmodified nanoparticles or aluminum hydroxide. Ultimately, compared with alum, this system offered superior protection in a mouse model of WN virus encephalitis. PMID:20660705

  7. Silent Circulation of St. Louis Encephalitis Virus Prior to an Encephalitis Outbreak in Cordoba, Argentina (2005)

    PubMed Central

    Díaz, Luis Adrian; Albrieu Llinás, Guillermo; Vázquez, Ana; Tenorio, Antonio; Contigiani, Marta Silvia

    2012-01-01

    St. Louis encephalitis virus is a complex zoonoses. In 2005, 47 laboratory-confirmed and probable clinical cases of SLEV infection were reported in Córdoba, Argentina. Although the causes of 2005 outbreak remain unknown, they might be related not only to virological factors, but also to ecological and environmental conditions. We hypothesized that one of the factors for SLE reemergence in Córdoba, Argentina, was the introduction of a new SLEV genotype (SLEV genotype III), with no previous activity in the area. In order to evaluate this hypothesis we carried out a molecular characterization of SLEV detections from mosquitoes collected between 2001 and 2004 in Córdoba city. A total of 315 mosquito pools (11,002 individuals) including 12 mosquitoes species were analyzed. Overall, 20 pools (8 mosquitoes species) were positive for SLEV. During this study, genotypes II, V and VII were detected. No mosquito pool infected with genotype III was detected before the 2005 outbreak. Genotype V was found every year and in the 8 sampled sites. Genotypes II and VII showed limited temporal and spatial activities. We cannot dismiss the association of genotype II and V as etiological agents during the outbreak. However, the silent circulation of other SLEV strains in Córdoba city before the 2005 outbreak suggests that the introduction of genotype III was an important factor associated to this event. Not mutually exclusive, other factors such as changes in avian hosts and mosquitoes vectors communities, driven by climatic and environmental modifications, should also be taken into consideration in further studies. PMID:22303490

  8. Recombinant protein production technology

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Recombinant protein production is an important technology for antibody production, biochemical activity study, and structural determination during the post-genomic era. Limiting factors in recombinant protein production include low-level protein expression, protein precipitation, and loss of protein...

  9. Sensitivity of the VecTest antigen assay for eastern equine encephalitis and western equine encephalitis viruses.

    PubMed

    Nasci, Roger S; Gottfried, Kristy L; Burkhalter, Kristen L; Ryan, Jeffrey R; Emmerich, Eva; Davé, Kirti

    2003-12-01

    VecTest assays for detecting eastern equine encephalitis virus (EEE) and western equine encephalitis virus (WEE) antigen in mosquito pools were evaluated to determine their sensitivity and specificity by using a range of EEE, WEE, St. Louis encephalitis virus (SLE), and West Nile virus (WN) dilutions as well as individual and pooled mosquitoes containing EEE or WEE. The EEE test produced reliable positive results with samples containing > or = 5.3 log10 plaque-forming units (PFU) of EEE/ml, and the WEE test produced reliable positive results with samples containing > or = 4.7 log10 PFU WEE/ml. Both assays detected the respective viral antigens in single virus-positive mosquitoes and in pools containing a single positive mosquito and 49 negative specimens. The SLE and WN assays also contained on the dipsticks accurately detected their respective viruses. No evidence was found of cross reaction or false positives in any of the tests. The VecTest assays were less sensitive than the EEE- and WEE-specific TaqMan reverse transcriptase polymerase chain reaction and Vero cell plaque assay, but appear to be useful for detecting arboviruses in mosquito-based arbovirus surveillance programs.

  10. Therapeutic Recombinant Monoclonal Antibodies

    ERIC Educational Resources Information Center

    Bakhtiar, Ray

    2012-01-01

    During the last two decades, the rapid growth of biotechnology-derived techniques has led to a myriad of therapeutic recombinant monoclonal antibodies with significant clinical benefits. Recombinant monoclonal antibodies can be obtained from a number of natural sources such as animal cell cultures using recombinant DNA engineering. In contrast to…

  11. NMR study of non-structural proteins--part II: (1)H, (13)C, (15)N backbone and side-chain resonance assignment of macro domain from Venezuelan equine encephalitis virus (VEEV).

    PubMed

    Makrynitsa, Garyfallia I; Ntonti, Dioni; Marousis, Konstantinos D; Tsika, Aikaterini C; Lichière, Julie; Papageorgiou, Nicolas; Coutard, Bruno; Bentrop, Detlef; Spyroulias, Georgios A

    2015-10-01

    Macro domains consist of 130-190 amino acid residues and appear to be highly conserved in all kingdoms of life. Intense research on this field has shown that macro domains bind ADP-ribose and other similar molecules, but their exact function still remains intangible. Macro domains are highly conserved in the Alphavirus genus and the Venezuelan equine encephalitis virus (VEEV) is a member of this genus that causes fatal encephalitis to equines and humans. In this study we report the high yield recombinant expression and preliminary solution NMR study of the macro domain of VEEV. An almost complete sequence-specific assignment of its (1)H, (15)N and (13)C resonances was obtained and its secondary structure predicted by TALOS+. The protein shows a unique mixed α/β-fold.

  12. Genetic recombination of tick-borne flaviviruses among wild-type strains.

    PubMed

    Norberg, Peter; Roth, Anette; Bergström, Tomas

    2013-06-05

    Genetic recombination has been suggested to occur in mosquito-borne flaviviruses. In contrast, tick-borne flaviviruses have been thought to evolve in a clonal manner, although recent studies suggest that recombination occurs also for these viruses. We re-analyzed the data and found that previous conclusions on wild type recombination were probably falsely drawn due to misalignments of nucleotide sequences, ambiguities in GenBank sequences, or different laboratory culture histories suggestive of recombination events in laboratory. To evaluate if reliable predictions of wild type recombination of tick-borne flaviviruses can be made, we analyzed viral strains sequenced exclusively for this study, and other flavivirus sequences retrieved from GenBank. We detected genetic signals supporting recombination between viruses within the three clades of TBEV-Eu, TBEV-Sib and TBEV-Fe, respectively. Our results suggest that the tick-borne encephalitis viruses may undergo recombination under natural conditions, but that geographic barriers restrict most recombination events to involve only closely genetically related viruses.

  13. Evidence for Recombination of Mitochondrial DNA in Triploid Crucian Carp

    PubMed Central

    Guo, Xinhong; Liu, Shaojun; Liu, Yun

    2006-01-01

    In this study, we report the complete mitochondrial DNA (mtDNA) sequences of the allotetraploid and triploid crucian carp and compare the complete mtDNA sequences between the triploid crucian carp and its female parent Japanese crucian carp and between the triploid crucian carp and its male parent allotetraploid. Our results indicate that the complete mtDNA nucleotide identity (98%) between the triploid crucian carp and its male parent allotetraploid was higher than that (93%) between the triploid crucian carp and its female parent Japanese crucian carp. Moreover, the presence of a pattern of identity and difference at synonymous sites of mitochondrial genomes between the triploid crucian carp and its parents provides direct evidence that triploid crucian carp possessed the recombination mtDNA fragment (12,759 bp) derived from the paternal fish. These results suggest that mtDNA recombination was derived from the fusion of the maternal and paternal mtDNAs. Compared with the haploid egg with one set of genome from the Japanese crucian carp, the diploid sperm with two sets of genomes from the allotetraploid could more easily make its mtDNA fuse with the mtDNA of the haploid egg. In addition, the triple hybrid nature of the triploid crucian carp probably allowed its better mtDNA recombination. In summary, our results provide the first evidence of mtDNA combination in polyploid fish. PMID:16322508

  14. The nsp3 Macrodomain Promotes Virulence in Mice with Coronavirus-Induced Encephalitis

    PubMed Central

    Fehr, Anthony R.; Athmer, Jeremiah; Channappanavar, Rudragouda; Phillips, Judith M.; Meyerholz, David K.

    2014-01-01

    ABSTRACT All coronaviruses encode a macrodomain containing ADP-ribose-1″-phosphatase (ADRP) activity within the N terminus of nonstructural protein 3 (nsp3). Previous work showed that mouse hepatitis virus strain A59 (MHV-A59) with a mutated catalytic site (N1348A) replicated similarly to wild-type virus but was unable to cause acute hepatitis in mice. To determine whether this attenuated phenotype is applicable to multiple disease models, we mutated the catalytic residue in the JHM strain of MHV (JHMV), which causes acute and chronic encephalomyelitis, using a newly developed bacterial artificial chromosome (BAC)-based MHV reverse genetics system. Infection of mice with the macrodomain catalytic point mutant virus (N1347A) resulted in reductions in lethality, weight loss, viral titers, proinflammatory cytokine and chemokine expression, and immune cell infiltration in the brain compared to mice infected with wild-type virus. Specifically, macrophages were most affected, with approximately 2.5-fold fewer macrophages at day 5 postinfection in N1347A-infected brains. Tumor necrosis factor (TNF) and interferon (IFN) signaling were not required for effective host control of mutant virus as all N1347A virus-infected mice survived the infection. However, the adaptive immune system was required for protection since N1347A virus was able to cause lethal encephalitis in RAG1−/− (recombination activation gene 1 knockout) mice although disease onset was modestly delayed. Overall, these results indicate that the BAC-based MHV reverse genetics system will be useful for studies of JHMV and expand upon previous studies, showing that the macrodomain is critical for the ability of coronaviruses to evade the immune system and promote viral pathogenesis. IMPORTANCE Coronaviruses are an important cause of human and veterinary diseases worldwide. Viral processes that are conserved across a family are likely to be good targets for the development of antiviral therapeutics and

  15. Rabies direct fluorescent antibody test does not inactivate rabies or eastern equine encephalitis viruses.

    PubMed

    Jarvis, Jodie A; Franke, Mary A; Davis, April D

    2016-08-01

    An examination using the routine rabies direct fluorescent antibody test was performed on rabies or Eastern equine encephalitis positive mammalian brain tissue to assess inactivation of the virus. Neither virus was inactivated with acetone fixation nor the routine test, thus laboratory employees should treat all samples as rabies and when appropriate Eastern equine encephalitis positive throughout the whole procedure.

  16. Catatonia in encephalitis and nonconvulsive seizures: a case report and review of the literature.

    PubMed

    Sahaya, Kinshuk; Lardizabal, David

    2010-03-01

    A 20-year-old woman was admitted for psychosis. On further investigation, she was found to be have viral encephalitis and generalized nonconvulsive seizures. After the seizures were controlled, she remained in a prolonged catatonic state. Repeated intravenous benzodiazepine administration, improved her cognition dramatically. This case emphasizes that catatonia may occur after encephalitis and nonconvulsive seizures.

  17. Recurrent aseptic encephalitis in periodic fever, aphthous stomatitis, pharyngitis and adenopathy (PFAPA) syndrome.

    PubMed

    Frye, Richard E

    2006-05-01

    An 11-year-old boy with episodes of periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) is reported. Two PFAPA episodes were associated with aseptic encephalitis and seizures. Recurrent acute aseptic encephalitis or seizures have never been reported during the febrile episodes of PFAPA. This possible association is discussed within the context of the etiology of PFAPA.

  18. Photoionization and Recombination

    NASA Technical Reports Server (NTRS)

    Nahar, Sultana N.

    2000-01-01

    Theoretically self-consistent calculations for photoionization and (e + ion) recombination are described. The same eigenfunction expansion for the ion is employed in coupled channel calculations for both processes, thus ensuring consistency between cross sections and rates. The theoretical treatment of (e + ion) recombination subsumes both the non-resonant recombination ("radiative recombination"), and the resonant recombination ("di-electronic recombination") processes in a unified scheme. In addition to the total, unified recombination rates, level-specific recombination rates and photoionization cross sections are obtained for a large number of atomic levels. Both relativistic Breit-Pauli, and non-relativistic LS coupling, calculations are carried out in the close coupling approximation using the R-matrix method. Although the calculations are computationally intensive, they yield nearly all photoionization and recombination parameters needed for astrophysical photoionization models with higher precision than hitherto possible, estimated at about 10-20% from comparison with experimentally available data (including experimentally derived DR rates). Results are electronically available for over 40 atoms and ions. Photoionization and recombination of He-, and Li-like C and Fe are described for X-ray modeling. The unified method yields total and complete (e+ion) recombination rate coefficients, that can not otherwise be obtained theoretically or experimentally.

  19. Japanese Experiment Module (JEM)

    NASA Technical Reports Server (NTRS)

    2003-01-01

    The Japanese Experiment Module (JEM) pressure module is removed from its shipping crate and moved across the floor of the Space Station Processing Facility at Kennedy Space Center (KSC) to a work stand. A research laboratory, the pressurized module is the first element of the JEM, named 'Kibo' (Hope) to arrive at KSC. Japan's primary contribution to the International Space Station, the module will enhance unique research capabilities of the orbiting complex by providing an additional environment in which astronauts will conduct experiments. The JEM also includes an exposed facility or platform for space environment experiments, a robotic manipulator system, and two logistics modules. The various JEM components will be assembled in space over the course of three Shuttle missions.

  20. Anthropophobia and Japanese performance.

    PubMed

    Takano, R

    1977-08-01

    Actors are not the only people who act on a regular basis--everyone does some "acting" in his everyday life. The merchant is acting when he pays compliments to his annoying customers. Neurotics often exaggerate their sufferings and assume poses in order to impress their therapists with the seriousness of their illness. When this acting is done so poorly that everyone but the person himself perceives its penny-dreadful nature, the neurosis might be designated a hysteria. Such dramatics can be observed not only in the demeanor of neurotics, but also in their symptoms. The unconscious and concealed acting revealed in the symptoms of neurotics, especially in those of anthropophobiacs, whose main concern is with their appearance in the eyes of others, is what I would like to examine in this paper. I will attempt to eludicate the psychopathology of a large element in Japanese neurosis--that is, of anthropophobia--in relation to unconscious acting.

  1. Molecular epidemiological study of enteroviruses associated with encephalitis in children from India.

    PubMed

    Kumar, Arvind; Shukla, Deepti; Kumar, Rashmi; Idris, Mohammad Z; Misra, Usha K; Dhole, Tapan N

    2012-11-01

    Enteroviruses have been reported in encephalitis cases. However, clinical and epidemiological characteristics of enteroviruses in encephalitis are not fully established. We prospectively investigated 204 children with encephalitis over a period of 2 years (2009 to 2010) for enterovirus. Enterovirus was detected in 45 specimens (22.1%); of these, 40 were typed by seminested reverse transcription-PCR (RT-PCR) and sequencing of the VP1 gene. Molecular typing of enterovirus revealed the predominance of echovirus 21 associated with an epidemic during the rainy seasons of 2010 and the circulation of echovirus 1, coxsackievirus B1, enterovirus 75, enterovirus 76, coxsackievirus B5, and echovirus 19. The nucleotide divergence among echovirus 21 strains was 0 to 2% at the nucleotide level. This study suggests that enterovirus is an important cause of encephalitis in children from India. To our knowledge, this is the first report of echovirus 21 in encephalitis cases worldwide.

  2. Japanese Management: An American Challenge.

    ERIC Educational Resources Information Center

    Rehder, Robert R.

    1979-01-01

    In contrast to the American system of management, Japanese management motivates its employees by challenging them with high goals and by providing inhouse training and development opportunities to meet their self-fulfillment needs. (Author/LD)

  3. Japanese attitudes towards foreign languages.

    PubMed

    Abe, Keiko

    2004-01-01

    The purpose of this study is to clarify Japanese attitudes towards foreign languages based on the kinds and changes of TV and radio programs that aired on the Japanese national broadcasting station (NHK) between 1955 and 2000. Foreign language programs are classified into three groups according to their content: 1) cultivation, 2) education, or 3) communication. For Japanese people, foreign languages are the measures of intelligence and intellect. Studying a foreign language is considered a sign of intelligence whether or not it is used for actual communication. The number of foreign language programs has increased tremendously since 1965 in part because the global economy has brought many countries in such close contact. Since 1990, programs for the purpose of communication have increased because of the necessity to communicate with foreign people. Japanese attitudes towards studying foreign languages have been changing gradually from an intellectual purpose to a communication purpose.

  4. The Japanese "Internment" Cases Revisited.

    ERIC Educational Resources Information Center

    Robinson, Edward T.

    2003-01-01

    Reviews topics discussed in the OAH article, "Incarcerating Japanese Americans" (Roger Daniels). States that the three internment cases were correct. Asks whether internment could re-occur given the climate in U.S. society since September 11, 2001. (CMK)

  5. Brainstem and limbic encephalitis with paraneoplastic neuromyelitis optica.

    PubMed

    Moussawi, Khaled; Lin, David J; Matiello, Marcelo; Chew, Sheena; Morganstern, Daniel; Vaitkevicius, Henrikas

    2016-01-01

    The spectrum of disorders associated with anti-neuromyelitis optica (NMO) antibody is being extended to include infrequent instances associated with cancer. We describe a patient with brainstem and limbic encephalitis from NMO-immunoglobulin G in serum and cerebrospinal fluid in the context of newly diagnosed breast cancer. The neurological features markedly improved with excision of her breast cancer and immune suppressive therapy. This case further broadens the NMO spectrum disorders (NMOSD) by an association between NMOSD and cancer and raises the question of coincidental occurrence and the appropriate circumstances to search for a tumor in certain instances of NMO.

  6. Ethical Implications of the Mild Encephalitis Hypothesis of Schizophrenia

    PubMed Central

    Riedmüller, Rita; Müller, Sabine

    2017-01-01

    Schizophrenia is a serious mental disease with a high mortality rate and severe social consequences. Due to insufficient knowledge about its etiopathogenesis, curative treatments are not available. One of the most promising new research concepts is the mild encephalitis hypothesis of schizophrenia, developed mainly by Karl Bechter and Norbert Müller. According to this hypothesis, a significant subgroup of schizophrenia patients suffer from a mild, but chronic, form of encephalitis with markedly different etiologies ranging from viral infections, traumas to autoimmune diseases. This inflammatory process is thought to occur in the beginning or during the course of the disease. In this article, we investigate the consequences of the mild encephalitis hypothesis of schizophrenia for the scientific community, and evaluate these consequences ethically. The mild encephalitis hypothesis implies that schizophrenia would no longer be considered an incurable psychiatric disorder. Instead, it would be considered a chronic, but treatable, neurological disease. This paradigm shift would doubtlessly have significant consequences: (1) major reforms would be necessary in the theoretical conceptualization of schizophrenia, which would challenge the psychiatric diagnostic systems, Diagnostic and Statistical Manual of Mental Disorders version 5 and ICD-10. (2) Psychotic patients should be treated in interdisciplinary teams, optimally in neuropsychiatric units; additionally, specialists for endocrinology, diabetology, and cardiology should be consulted for the frequently occuring somatic comorbidities. (3) Current diagnostic procedures and (4) therapies would have to be modified significantly. (5) There might be repercussions for the pharmaceutical industry as well: first, because old drugs with expired patent protection could partly replace expensive drugs and, second, because there would be a demand for the development of new anti-inflammatory drugs. (6) Legal evaluation of

  7. Efficacy of eastern equine encephalitis immunization in whooping cranes.

    PubMed

    Olsen, G H; Turell, M J; Pagac, B B

    1997-04-01

    An epizootic of eastern equine encephalitis (EEE) at the Patuxent Wildlife Research Center (PWRC), Laurel, Maryland (USA), in 1989 provided an opportunity to determine if EEE immunization protected whooping cranes (Grus americana). Based on seroconversion of 31% of sympatric hatch-year sandhill cranes, Grus canadensis, and a previous 35% case fatality rate in whooping cranes, 17 (37%) of the 46 susceptible whooping cranes should have been exposed to virus and six should have died. As there were no deaths in these birds, the EEE vaccination program appeared to be efficacious in this whooping crane population.

  8. Herpes Simplex Encephalitis Complicated by Cerebral Hemorrhage during Acyclovir Therapy

    PubMed Central

    Harada, Yukinori; Hara, Yuuta

    2017-01-01

    Herpes simplex encephalitis (HSE) can be complicated by adverse events in the acute phase. We herein present the case of a 71-year-old woman with HSE complicated by cerebral hemorrhage. She presented with acute deterioration of consciousness and fever and was diagnosed with HSE based on the detection of herpes simplex virus-1 in the cerebrospinal fluid by a polymerase chain reaction. The cerebral hemorrhage developed during acyclovir therapy; however, its diagnosis was delayed for 2 days. After the conservative treatment of the cerebral hemorrhage, the patient made a near-complete recovery. Cerebral hemorrhage should be considered as an acute-phase complication of HSE. PMID:28090058

  9. Efficacy of eastern encephalitis immunization in whooping cranes

    USGS Publications Warehouse

    Olsen, G.H.; Turell, M.J.; Pagac, B.B.

    1997-01-01

    An epizootic of eastern equine encephalitis (EEE) at the Patuxent Wildlife Research Center (PWRC), Laurel, Maryland (USA), in 1989 provided an opportunity to determine if EEE immunization protected whooping cranes (Grus americana). Based on seroconversion of 31 % of sympatric hatch-year sandhill cranes, Grus canadensis, and a previous 35% case fatality rate in whooping cranes, 17 (37%) of the 46 susceptible whooping cranes should have been exposed to virus and six should have died. As there were no deaths in these birds, the EEE vaccination program appeared to be efficacious in this whooping crane population.

  10. Extratemporal herpes encephalitis during natalizumab treatment: A case report.

    PubMed

    Haggiag, Shalom; Prosperini, Luca; Galgani, Simonetta; Pozzilli, Carlo; Pinnetti, Carmela

    2016-11-01

    Herpes simplex virus encephalitis (HSE) is a rare but often fatal disease if left untreated. MRI typically shows the characteristic findings of medial temporal lobe and insular involvement, while diagnosis in confirmed by CSF PCR. In immunocompromised state, HSE may have atypical clinical and radiological features. We report a MS patient under natalizumab treatment with HSE, who presented with MRI lesions exclusively in the right parietal lobe. The patient was timely started on acyclovir resulting in marked improvement. A high index of suspicion for HSE should be maintained when a patient presents with fever and extratemporal lesions, even more in immunocompromised subjects.

  11. Herpes Simplex Encephalitis Complicated by Cerebral Hemorrhage during Acyclovir Therapy.

    PubMed

    Harada, Yukinori; Hara, Yuuta

    2017-01-01

    Herpes simplex encephalitis (HSE) can be complicated by adverse events in the acute phase. We herein present the case of a 71-year-old woman with HSE complicated by cerebral hemorrhage. She presented with acute deterioration of consciousness and fever and was diagnosed with HSE based on the detection of herpes simplex virus-1 in the cerebrospinal fluid by a polymerase chain reaction. The cerebral hemorrhage developed during acyclovir therapy; however, its diagnosis was delayed for 2 days. After the conservative treatment of the cerebral hemorrhage, the patient made a near-complete recovery. Cerebral hemorrhage should be considered as an acute-phase complication of HSE.

  12. Comprehensive Mapping of Common Immunodominant Epitopes in the Eastern Equine Encephalitis Virus E2 Protein Recognized by Avian Antibody Responses

    PubMed Central

    Sun, EnCheng; Zhao, Jing; Sun, Liang; Xu, QingYuan; Yang, Tao; Qin, YongLi; Wang, WenShi; Wei, Peng; Sun, Jing; Wu, DongLai

    2013-01-01

    Eastern equine encephalitis virus (EEEV) is a mosquito-borne virus that can cause both human and equine encephalitis with high case fatality rates. EEEV can also be widespread among birds, including pheasants, ostriches, emu, turkeys, whooping cranes and chickens. The E2 protein of EEEV and other Alphaviruses is an important immunogenic protein that elicits antibodies of diagnostic value. While many therapeutic and diagnostic applications of E2 protein-specific antibodies have been reported, the specific epitopes on E2 protein recognized by the antibody responses of different susceptible hosts, including avian species, remain poorly defined. In the present study, the avian E2-reactive polyclonal antibody (PAb) response was mapped to linear peptide epitopes using PAbs elicited in chickens and ducks following immunization with recombinant EEEV E2 protein and a series of 42 partially overlapping peptides covering the entire EEEV E2 protein. We identified 12 and 13 peptides recognized by the chicken and duck PAb response, respectively. Six of these linear peptides were commonly recognized by PAbs elicited in both avian species. Among them five epitopes recognized by both avian, the epitopes located at amino acids 211–226 and 331–352 were conserved among the EEEV antigenic complex, but not other associated alphaviruses, whereas the epitopes at amino acids 11–26, 30–45 and 151–166 were specific to EEEV subtype I. The five common peptide epitopes were not recognized by avian PAbs against Avian Influenza Virus (AIV) and Duck Plague Virus (DPV). The identification and characterization of EEEV E2 antibody epitopes may be aid the development of diagnostic tools and facilitate the design of epitope-based vaccines for EEEV. These results also offer information with which to study the structure of EEEV E2 protein. PMID:23922704

  13. Comprehensive mapping of common immunodominant epitopes in the eastern equine encephalitis virus E2 protein recognized by avian antibody responses.

    PubMed

    Sun, Encheng; Zhao, Jing; Sun, Liang; Xu, Qingyuan; Yang, Tao; Qin, Yongli; Wang, Wenshi; Wei, Peng; Sun, Jing; Wu, Donglai

    2013-01-01

    Eastern equine encephalitis virus (EEEV) is a mosquito-borne virus that can cause both human and equine encephalitis with high case fatality rates. EEEV can also be widespread among birds, including pheasants, ostriches, emu, turkeys, whooping cranes and chickens. The E2 protein of EEEV and other Alphaviruses is an important immunogenic protein that elicits antibodies of diagnostic value. While many therapeutic and diagnostic applications of E2 protein-specific antibodies have been reported, the specific epitopes on E2 protein recognized by the antibody responses of different susceptible hosts, including avian species, remain poorly defined. In the present study, the avian E2-reactive polyclonal antibody (PAb) response was mapped to linear peptide epitopes using PAbs elicited in chickens and ducks following immunization with recombinant EEEV E2 protein and a series of 42 partially overlapping peptides covering the entire EEEV E2 protein. We identified 12 and 13 peptides recognized by the chicken and duck PAb response, respectively. Six of these linear peptides were commonly recognized by PAbs elicited in both avian species. Among them five epitopes recognized by both avian, the epitopes located at amino acids 211-226 and 331-352 were conserved among the EEEV antigenic complex, but not other associated alphaviruses, whereas the epitopes at amino acids 11-26, 30-45 and 151-166 were specific to EEEV subtype I. The five common peptide epitopes were not recognized by avian PAbs against Avian Influenza Virus (AIV) and Duck Plague Virus (DPV). The identification and characterization of EEEV E2 antibody epitopes may be aid the development of diagnostic tools and facilitate the design of epitope-based vaccines for EEEV. These results also offer information with which to study the structure of EEEV E2 protein.

  14. [A Case of Clinically Mild Encephalitis/encephalopathy with a Reversible Splenial Lesion due to Dengue Fever].

    PubMed

    Saito, Nobuo; Kitashouji, Emi; Kojiro, Maiko; Furumoto, Akitugu; Morimoto, Konosuke; Morita, Kouichi; Ariyoshi, Koya

    2015-07-01

    Clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) has been recently proposed as a clinical-radiological syndrome. Several causes of MERS have been reported including infectious diseases. We present herein on a case of MERS induced by dengue fever in a Japanese traveler. A 48-year-old male returning from Thailand and Cambodia was admitted for an unknown fever. Following admission, the dengue virus was diagnosed with a positive RT-PCR result. On day 5 of the illness, regardless of reduced fever, weakness suddenly developed in both upper limbs. A cerebral MRI showed hyperintensities in the splenium of the corpus callosum on T2-weighted and diffusion-weighted images. The symptoms resolved completely within two days of onset. The patient was diagnosed as having MERS due to the MRI features and the mild clinical course. Although only a few cases of MERS caused by dengue fever have been reported, the condition is possibly underdiagnosed. It is hypothesized that dengue fever can induce MERS as dengue fever can cause increased endothelium permeability and hypo-sodium which have been proposed in the pathogenesis of MERS. However, there is currently limited evidence for this. Further research is recommended to demonstrate a causal association between dengue fever and MERS.

  15. Recombination of cluster ions

    NASA Technical Reports Server (NTRS)

    Johnsen, Rainer

    1993-01-01

    Some of our recent work on molecular band emissions from recombination of molecular dimer ions (N4(+) and CO(+) CO) is discussed. Much of the experimental work was done by Y. S. Cao; the results on N4(+) recombination have been published. A brief progress report is given on our ongoing measurements of neutral products of recombination using the flowing-afterglow Langmuir-probe technique in conjunction with laser-induced fluorescence.

  16. Production of recombinant allergens in plants

    PubMed Central

    2010-01-01

    A large percentage of allergenic proteins are of plant origin. Hence, plant-based expression systems are considered ideal for the recombinant production of certain allergens. First attempts to establish production of plant-derived allergens in plants focused on transient expression in Nicotiana benthamiana infected with recombinant viral vectors. Accordingly, allergens from birch and mugwort pollen, as well as from apple have been expressed in plants. Production of house dust mite allergens has been achieved by Agrobacterium-mediated transformation of tobacco plants. Beside the use of plants as production systems, other approaches have focused on the development of edible vaccines expressing allergens or epitopes thereof, which bypasses the need of allergen purification. The potential of this approach has been convincingly demonstrated for transgenic rice seeds expressing seven dominant human T cell epitopes derived from Japanese cedar pollen allergens. Parallel to efforts in developing recombinant-based diagnostic and therapeutic reagents, different gene-silencing approaches have been used to decrease the expression of allergenic proteins in allergen sources. In this way hypoallergenic ryegrass, soybean, rice, apple, and tomato were developed. PMID:21258627

  17. The case for immunomodulatory approaches in treating HSV encephalitis

    PubMed Central

    Ramakrishna, Chandran; Openshaw, Harry; Cantin, Edouard M

    2013-01-01

    HSV encephalitis (HSE) is the most prevalent sporadic viral encephalitis. Although safe and effective antiviral therapies and greatly improved noninvasive diagnostic procedures have significantly improved outcomes, mortality (~20%) and debilitating neurological sequelae in survivors remain unacceptably high. An encouraging new development is that the focus is now shifting away from the virus exclusively, to include consideration of the host immune response to infection in the pathology underlying development of HSE. In this article, the authors discuss results from recent studies in experimental mouse models, as well as clinical reports that demonstrate a role for exaggerated host inflammatory responses in the brain in the development of HSE that is motivating researchers and clinicians to consider new therapeutic approaches for treating HSE. The authors also discuss results from a few studies that have shown that immunomodulatory drugs can be highly protective against HSE, which supports a role for deleterious host inflammatory responses in HSE. The impressive outcomes of some immunomodulatory approaches in mouse models of HSE emphasize the urgent need for clinical trials to rigorously evaluate combination antiviral and immunomodulatory therapy in comparison with standard antiviral therapy for treatment of HSE, and support for such an initiative is gaining momentum. PMID:23956785

  18. Neuropsychological and psychiatric profiles in acute encephalitis in adults.

    PubMed

    Pewter, Stephen M; Williams, W Huw; Haslam, Catherine; Kay, Janice M

    2007-01-01

    Acute encephalitis is an inflammation of brain tissue that can result from activity in the central nervous system (CNS) of a number of viruses. Although the neurological and psychiatric effects of encephalitis in the acute phase of the illness are well-known (Caroff, Mann, Gliatto, Sullivan, & Campbell, 2001), larger scale studies of the pattern of neuropsychological and psychiatric impairment following recovery from the acute inflammatory phase are less apparent. This paper reports the results of neuropsychological testing with a range of standardised cognitive measures in a case series of long-term post-acute participants. Psychiatric abnormality is examined using the SCL-90-R self-report scale of distress (Derogatis, 1983). We also examined the role of emerging insight in the aetiology of depression in this population. Two clusters of cognitive dysfunction were observed, one group of primarily herpes simplex cases showing a severe generalised deficit across a number of cognitive domains and a second cluster showing a variety of more isolated disorders of executive function. Abnormally high levels of distress were reported by participants, with depression, obsessive-compulsive symptoms, interpersonal sensitivity and phobic anxiety most significantly increased. Depression was found to be least severe in those with most accurate insight into their problems. Examining the correlations between cognitive and psychiatric test results demonstrates a relationship between depression and interpersonal anxiety and specific cognitive measures. Obsessive-compulsive behaviour and phobic anxiety, however, appear to exist independently of the assessed cognitive deficits.

  19. IL-22 signaling contributes to West Nile encephalitis pathogenesis.

    PubMed

    Wang, Penghua; Bai, Fengwei; Zenewicz, Lauren A; Dai, Jianfeng; Gate, David; Cheng, Gong; Yang, Long; Qian, Feng; Yuan, Xiaoling; Montgomery, Ruth R; Flavell, Richard A; Town, Terrence; Fikrig, Erol

    2012-01-01

    The Th17 cytokine, IL-22, regulates host immune responses to extracellular pathogens. Whether IL-22 plays a role in viral infection, however, is poorly understood. We report here that Il22(-/-) mice were more resistant to lethal West Nile virus (WNV) encephalitis, but had similar viral loads in the periphery compared to wild type (WT) mice. Viral loads, leukocyte infiltrates, proinflammatory cytokines and apoptotic cells in the central nervous system (CNS) of Il22(-/-) mice were also strikingly reduced. Further examination showed that Cxcr2, a chemokine receptor that plays a non-redundant role in mediating neutrophil migration, was significantly reduced in Il22(-/-) compared to WT leukocytes. Expression of Cxcr2 ligands, cxcl1 and cxcl5, was lower in Il22(-/-) brains than wild type mice. Correspondingly, neutrophil migration from the blood into the brain was attenuated following lethal WNV infection of Il22(-/-) mice. Our results suggest that IL-22 signaling exacerbates lethal WNV encephalitis likely by promoting WNV neuroinvasion.

  20. Neospora caninum as causative agent of bovine encephalitis in Brazil.

    PubMed

    Malaguti, Jane Mary Albinati; Cabral, Aline Diniz; Abdalla, Raisa Pereira; Salgueiro, Yolanda Oliveira; Galleti, Nara Thiers Cacciatori; Okuda, Liria Hiromi; Cunha, Elenice Maria Sequetin; Pituco, Edviges Maristela; Del Fava, Claudia

    2012-01-01

    For supporting the Brazilian bovine encephalitis surveillance program this study examined the differential diagnosis of Neospora caninum in central nervous system (CNS) by histological analysis (HE staining), immunohistochemistry (IHC), and nested-PCR using a set of primers from the Nc5 region of the genomic DNA and ITS1 region of the ribosomal DNA. A sample of 302 cattle presenting neurological syndrome and negative for rabies, aged 0 to 18 years, from herds in 10 Brazilian states was evaluated for N. caninum from January 2007 to April 2010. All specimens tested negative with IHC and nested-PCR using primers from the ITS1 region of ribosomal DNA, while two positive cases (0.66%) were found using primers from the Nc5 region of genomic DNA: a 20 month-old male and a 72 month-old female, both from São Paulo State. Only the male presented severe multifocal necrotizing encephalitis associated with mononuclear cell infiltration, a pathognomonic lesion caused by parasites of the family Sarcocystidae, and only this case was associated with N. caninum thus representing 0.33% positivity. Future studies should explore the association of IHC and nested-PCR with real-time PCR, a quantitative method that could be standardized for improving the detection of N. caninum in bovine CNS specimens.

  1. Disgust and fear recognition in paraneoplastic limbic encephalitis.

    PubMed

    Sprengelmeyer, Reiner; Atkinson, Anthony P; Sprengelmeyer, Anke; Mair-Walther, Johanna; Jacobi, Christian; Wildemann, Brigitte; Dittrich, Winand H; Hacke, Werner

    2010-05-01

    Paraneoplastic limbic encephalitis (PNLE) affects limbic portions of the brain associated with recognition of social signals of emotions. Yet it is not known whether this perceptual ability is impaired in individuals with PNLE. We therefore conducted a single case study to explore possible impairments in recognising facially, vocally and bodily expressed emotions, using standardised emotion recognition tests. Facial expression recognition was tested with two forced-choice emotion-labelling tasks using static faces with either prototypical or morphed blends of basic emotions. Recognition of vocally and bodily expressed emotions was also tested with forced-choice labelling tasks, one based on prosodic cues, the other on whole-body movement cues. We found a deficit in fear and disgust recognition from both face and voice, while recognition of bodily expressed emotions was unaffected. These findings are consistent with data from previous studies demonstrating critical roles for certain brain regions - particularly the amygdala and insular cortex - in processing facially and vocally displayed basic emotions, and furthermore, suggest that recognition of bodily expressed emotions may not depend on neural structures involved in facial and vocal emotion recognition. Impaired facial and vocal emotion recognition may form a further neuropsychological marker of limbic encephalitis, in addition to the already well-described mnestic deficits.

  2. Acute hemorrhagic encephalitis: An unusual presentation of dengue viral infection

    PubMed Central

    Nadarajah, Jeyaseelan; Madhusudhan, Kumble Seetharama; Yadav, Ajay Kumar; Gupta, Arun Kumar; Vikram, Naval Kumar

    2015-01-01

    Dengue is a common viral infection worldwide with presentation varying from clinically silent infection to dengue fever, dengue hemorrhagic fever, and severe fulminant dengue shock syndrome. Neurological manifestation usually results from multisystem dysfunction secondary to vascular leak. Presentation as hemorrhagic encephalitis is very rare. Here we present the case of a 13-year-old female admitted with generalized tonic clonic seizures. Plain computed tomography (CT) scan of head revealed hypodensities in bilateral deep gray matter nuclei and right posterior parietal lobe without any hemorrhage. Cerebrospinal fluid (CSF) and serology were positive for IgM and IgG antibodies to dengue viral antigen. Contrast-enhanced magnetic resonance imaging (MRI) revealed multifocal T2 and fluid attenuated inversion recovery (FLAIR) hyperintensities in bilateral cerebral parenchyma including basal ganglia. No hemorrhage was seen. She was managed with steroids. As her clinical condition deteriorated, after being stable for 2 days, repeat MRI was done which revealed development of hemorrhage within the lesions, and diagnosis of acute hemorrhagic encephalitis of dengue viral etiology was made. PMID:25709166

  3. Acute hemorrhagic encephalitis: An unusual presentation of dengue viral infection.

    PubMed

    Nadarajah, Jeyaseelan; Madhusudhan, Kumble Seetharama; Yadav, Ajay Kumar; Gupta, Arun Kumar; Vikram, Naval Kumar

    2015-01-01

    Dengue is a common viral infection worldwide with presentation varying from clinically silent infection to dengue fever, dengue hemorrhagic fever, and severe fulminant dengue shock syndrome. Neurological manifestation usually results from multisystem dysfunction secondary to vascular leak. Presentation as hemorrhagic encephalitis is very rare. Here we present the case of a 13-year-old female admitted with generalized tonic clonic seizures. Plain computed tomography (CT) scan of head revealed hypodensities in bilateral deep gray matter nuclei and right posterior parietal lobe without any hemorrhage. Cerebrospinal fluid (CSF) and serology were positive for IgM and IgG antibodies to dengue viral antigen. Contrast-enhanced magnetic resonance imaging (MRI) revealed multifocal T2 and fluid attenuated inversion recovery (FLAIR) hyperintensities in bilateral cerebral parenchyma including basal ganglia. No hemorrhage was seen. She was managed with steroids. As her clinical condition deteriorated, after being stable for 2 days, repeat MRI was done which revealed development of hemorrhage within the lesions, and diagnosis of acute hemorrhagic encephalitis of dengue viral etiology was made.

  4. Human-like antibodies neutralizing Western equine encephalitis virus

    PubMed Central

    Hülseweh, Birgit; Rülker, Torsten; Pelat, Thibaut; Langermann, Claudia; Frenzel, Andrè; Schirrmann, Thomas; Dübel, Stefan; Thullier, Philippe; Hust, Michael

    2014-01-01

    This study describes the development of the first neutralizing antibodies against Western equine encephalitis virus (WEEV), a member of the genus Alphavirus. WEEV is transmitted by mosquitoes and can spread to the human central nervous system, causing symptoms ranging from mild febrile reactions to life-threatening encephalitis. WEEV has been classified as a biological warfare agent by the US Centers for Disease Control and Prevention. No anti-WEEV drugs are currently commercially available. Neutralizing antibodies are useful for the pre- and post-exposure treatment of WEEV infections. In this study, two immune antibody gene libraries were constructed from two macaques immunized with inactivated WEEV. Four antibodies were selected from these libraries and recloned as scFv-Fc, with a human Fc part. These antibodies bound WEEV specifically in ELISA with little or no cross-reaction with other alphaviruses. They were further analyzed by immunohistochemistry. All binders were suitable for the intracellular detection of WEEV particles. Neutralizing activity was determined in vitro. Three of the four antibodies were found to be neutralizing; about 1 ng/mL of the best antibody (ToR69–3A2) neutralized 50% of 5x104 TCID50/mL. Due to its human-like nature with a germinality index of 89% (VH) and 91% (VL), the ToR69–3A2 antibody is a promising candidate for future passive vaccine development. PMID:24518197

  5. HIV-2 encephalitis: case report and literature review.

    PubMed

    Wood, Brian R; Klein, Joshua P; Lyons, Jennifer L; Milner, Danny A; Phillips, Richard E; Schutten, Martin; Folkerth, Rebecca D; Ciarlini, Pedro; Henrich, Timothy J; Johnson, Jennifer A

    2012-07-01

    We report the case of a 59-year-old man who moved from Cape Verde to Massachusetts at the age of 29. He had multiple sexual contacts with female partners in Cape Verde and with West African women in Massachusetts, as well as multiple past indeterminate HIV-1 antibody tests. He presented to our facility with 2-3 months of inappropriate behaviors, memory impairment, weight loss, and night sweats, at which time he was found to have an abnormal enhancing lesion of the corpus collosum on brain magnetic resonance imaging (MRI). Laboratory testing revealed a CD4 count of 63 cells/mm(3), positive HIV-2 Western blot, serum HIV-2 RNA polymerase chain reaction (PCR) of 1160 copies per milliliter and cerebrospinal fluid (CSF) HIV-2 RNA PCR of 2730 copies per milliliter. Brain biopsy demonstrated syncytial giant cells centered around small blood vessels and accompanied by microglia, which correlated with prior pathologic descriptions of HIV-2 encephalitis and with well-described findings of HIV-1 encephalitis. Based on genotype resistance assay results, treatment guidelines, and prior studies validating success with lopinavir-ritonavir, he was treated with tenofovir-emtricitabine and lopinavir-ritonavir, which has led to virologic suppression along with steady neurologic and radiologic improvement, although he continues to have deficits.

  6. An autopsy case of amebic meningoencephalitis. The first Japanese case caused by Balamuthia mandrillaris.

    PubMed

    Shirabe, Teruo; Monobe, Yasumasa; Visvesvara, Govinda S

    2002-09-01

    We report here the first case of amebic meningoencephalitis caused by Balamuthia mandrillaris in a 78-year-old Japanese woman with Sjögren's syndrome. Fourteen days before her death, she presented with high fever and lost consciousness and later developed neck stiffness and abducens palsy. Computed tomography scans of the brain demonstrated multiple low-density areas throughout the brain. Neuropathologically, hemorrhagic and necrotic lesions with many amebic trophozoites were scattered in the brain and spinal cord. Granulomatous lesions were only rarely found. The amebas were identified as Balamuthia mandrillaris based on immunofluorescence assay. Clinicopathologically, our case was thought to be an intermediate between primary amebic meningoencephalitis due to Negleria fowleri and granulomatous amebic encephalitis due to Acanthameba species. Essentially, the case was one of an elderly person with suspected immunodeficiency with fulminant necrotic meningoencephalitis and scanty granulomatous lesions of 14 days course.

  7. [Anti-NMDA encephalitis in psychiatry; malignant catatonia, atypical psychosis and ECT].

    PubMed

    Kanbayashi, Takashi; Tsutsui, Ko; Tanaka, Keiko; Omori, Yuki; Takaki, Manabu; Omokawa, Mayu; Mori, Akane; Kusanagi, Hiroaki; Nishino, Seiji; Shimizu, Tetsuo

    2014-01-01

    The symptoms of malignant (lethal) catatonia has been reported similar to initial symptoms of anti-NMDAR encephalitis. Subsequently, this autoimmune limbic encephalitis has been noticed in many psychiatrists. We have experienced several cases with malignant catatonia having anti-NMDAR antibody without clinical signs of encephalitis. Thereafter, we have also found anti-NMDAR antibody positive patients of young females with acute florid psychiatric symptoms without clinical signs of encephalitis. The features of these patients mirror-those of "Atypical psychosis" proposed by Mitsuda in Japan, a notion derived from "Cycloid psychosis" conceptualized by German psychiatrist, Leonhard. Both cycloid and atypical psychosis have coinciding features of acute onset, emotional disturbances, psychomotor disturbances, alternations of consciousness, high prevalence in women and oriented premorbid personality. Both malignant catatonia and atypical psychosis have been known to be effectively treated with modified electro convulsion therapy (m-ECT). Our 5 cases with anti-NMDAR antibody, m-ECT treatments were effective. Infectious encephalitis is contra indication of m-ECT, but this autoimmune encephalitis would be careful indication. Schizophrenia is a common, heterogeneous, and complex disorder with unknown etiology. There is established evidence of NMDAR hypofunction as a central component of the functional disconnectivity; this is one of the most accepted models for schizophrenia. Moreover, autoimmune mechanisms have been proposed to be involved, at least in subgroups of schizophrenia patients. Further research of anti-NMDAR antibody and encephalitis would be important clues for the investigation of schizophrenia, catatonia and atypical psychosis.

  8. Language Attitudes in the Second Generation Japanese Group in Melbourne.

    ERIC Educational Resources Information Center

    Nasu, Tsuneo

    This study investigated language attitudes and Japanese language maintenance among a group of second-generation Japanese in Melbourne (Australia). Subjects were 66 Japanese high school students (second-generation) attending Japanese-language schools and 109 Japanese mothers (first-generation) self-identified as Japanese-identity,…

  9. Anti-N-methyl-d-aspartate receptor encephalitis: review of clinical presentation, diagnosis and treatment

    PubMed Central

    Barry, Helen; Byrne, Susan; Barrett, Elizabeth; Murphy, Kieran C.; Cotter, David R.

    2015-01-01

    Anti-N-methyl-d-aspartate (NMDA) receptor encephalitis is a form of encephalitis occurring primarily in women and associated with antibodies against NR1 or NR2 subunits of the NMDA receptor. As a potentially treatable differential for symptoms and signs seen in neurology and psychiatric clinics, clinicians practising across the lifespan should be aware of this form of encephalitis. Common clinical features include auditory and visual hallucinations, delusions, behavioural change (frequently with agitation), impaired consciousness, motor disturbance (ranging from dyskinesia to catatonia), seizures, and autonomic dysfunction. We present a review of the literature on the disorder, including its clinical presentation, differential diagnosis, epidemiology, treatment and prognosis. PMID:26191419

  10. Anti-N-methyl-d-aspartate receptor encephalitis: review of clinical presentation, diagnosis and treatment.

    PubMed

    Barry, Helen; Byrne, Susan; Barrett, Elizabeth; Murphy, Kieran C; Cotter, David R

    2015-02-01

    Anti-N-methyl-d-aspartate (NMDA) receptor encephalitis is a form of encephalitis occurring primarily in women and associated with antibodies against NR1 or NR2 subunits of the NMDA receptor. As a potentially treatable differential for symptoms and signs seen in neurology and psychiatric clinics, clinicians practising across the lifespan should be aware of this form of encephalitis. Common clinical features include auditory and visual hallucinations, delusions, behavioural change (frequently with agitation), impaired consciousness, motor disturbance (ranging from dyskinesia to catatonia), seizures, and autonomic dysfunction. We present a review of the literature on the disorder, including its clinical presentation, differential diagnosis, epidemiology, treatment and prognosis.

  11. Naegleria fowleri-associated encephalitis in a cow from Costa Rica.

    PubMed

    Morales, Juan A; Chaves, Aida J; Visvesvara, G S; Dubey, J P

    2006-06-30

    Species of Naegleria, Acanthamoeba, and Balamuthia are soil amoebae that can cause encephalitis in animals and humans. Of these, Naegleria fowleri is the cause of often fatal primary meningoencephalitis in humans. N. fowleri-associated encephalitis was diagnosed in a cow that was suspected to have rabies. Only formalin-fixed brain was available for diagnosis. There was severe meningoencephalitis involving all parts of the brain and numerous amoebic trophozoites were present in lesions. The amoebae reacted with N. fowleri-specific polyclonal antibodies in an indirect immunofluorescent antibody test. This is the first report of amoebic encephalitis in any host from Costa Rica.

  12. Unilateral predominance of abnormal movements: A characteristic feature of the pediatric anti-NMDA receptor encephalitis?

    PubMed

    Benjumea-Cuartas, Vanessa; Eisermann, Monika; Simonnet, Hina; Hully, Marie; Nabbout, Rima; Desguerre, Isabelle; Kaminska, Anna

    2017-01-01

    Anti-NMDA receptor encephalitis is a treatable autoimmune disease characterized by cognitive, motor and psychiatric features that primarily affects young adults and children. We present a case of a 7-year-old boy with asymmetrical (mainly right hemibody) and abnormal polymorphic movements without concomitant scalpictal EEG changes but had background slowing predominating over the left hemisphere. This report illustrates previous descriptions of asymmetric presentation of abnormal movements in pediatric anti-NMDA receptor encephalitis and emphasizes the importance of video-EEG interpreted within the overall clinical context, to differentiate epileptic from non-epileptic abnormal movements in patients with autoimmune encephalitis.

  13. Anti-NMDA receptor encephalitis: a neurological disease in psychiatric disguise.

    PubMed

    Sharma, Bhawna; Handa, Rahul; Prakash, Swayam; Nagpal, Kadam; Gupta, Pankaj

    2014-02-01

    Anti-NMDA receptor encephalitis was first described in 2005 when psychiatric features, memory loss and altered consciousness were found in four women with ovarian teratoma. We report a case of anti-NMDA receptor encephalitis in a 16-year-old female who presented with psychiatric features followed by autonomic dysfunction and orofacial dyskinesias that showed drastic improvement to intravenous immunoglobulin. As many patients of anti-NMDAR encephalitis initially present with psychiatric features, it is important for psychiatrists to have high index of suspicion for this disease and thus avoid the delay in diagnosing this treatable condition which may be otherwise fatal.

  14. Anti-NMDA receptor encephalitis: an easily missed diagnosis in older patients.

    PubMed

    Rainey, Katie; Gholkar, Bethan; Cheesman, Mark

    2014-09-01

    Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is an important, treatable cause of encephalitis which remains under-recognised despite a growing body of the literature [1]. It is an immune-mediated syndrome which presents with a variety of neurological symptoms including headache, fever, personality change and seizures. Most case reports to date are of young adults, it is much less frequently reported in older adults. The syndrome has been associated with ovarian teratomas. The prognosis is good with early recognition and treatment, though may relapse. We present a case of NMDA encephalitis in an elderly patient who responded well to immunosuppressive therapy.

  15. Prolonged acyclovir treatment in a child with opercular syndrome related to herpes simplex encephalitis.

    PubMed

    Karli, Arzu; Şensoy, Gülnar; Tekin, Emine; Sofuoğlu, Ayşe I; Bilgici, Meltem C; Özyürek, Hamit

    HSV 1 encephalitis is the most common cause of sporadic and focal viral encephalitis. Opercular syndrome is characterized by swallowing and speech difficulties which are associated with deterioration of voluntary control of face, pharynx, tongue and chewing muscles. It can be developed in patients with Herpes simplex encephalitis (HSE). Here, a twelve-year-old boy who was diagnosed with HSE and Opercular syndrome, is presented. The patient recovered without sequela as a result of 30 days of intravenous and 10 days of oral acyclovir treatment. It might be important as well, to personalize and elongate the treatment in terms of prognosis.

  16. BK Virus Encephalitis in HIV-Infected Patients: Case Report and Review

    PubMed Central

    Antoniolli, Luciana; Borges, Rafael

    2017-01-01

    Encephalitis and meningitis due to BKPyV are unusual and emerging condition. Only a few cases of BKPyV encephalitis have been reported in hematopoietic stem cell transplant recipients, with the majority of cases presenting with concurrent hemorrhagic cystitis and HIV-infected patients. The authors report two HIV-infected patients with the diagnosis of BKPyV encephalitis and discuss the main clinical, diagnostic, and therapeutic aspects of this infection in patients with AIDS. Physicians should be aware to recognize the main clinical features and diagnose BKPyV central nervous infection in the setting of AIDS. PMID:28326104

  17. Novel vaccine against Venezuelan equine encephalitis combines advantages of DNA immunization and a live attenuated vaccine.

    PubMed

    Tretyakova, Irina; Lukashevich, Igor S; Glass, Pamela; Wang, Eryu; Weaver, Scott; Pushko, Peter

    2013-02-04

    DNA vaccines combine remarkable genetic and chemical stability with proven safety and efficacy in animal models, while remaining less immunogenic in humans. In contrast, live-attenuated vaccines have the advantage of inducing rapid, robust, long-term immunity after a single-dose vaccination. Here we describe novel iDNA vaccine technology that is based on an infectious DNA platform and combines advantages of DNA and live attenuated vaccines. We applied this technology for vaccination against infection with Venezuelan equine encephalitis virus (VEEV), an alphavirus from the Togaviridae family. The iDNA vaccine is based on transcription of the full-length genomic RNA of the TC-83 live-attenuated virus from plasmid DNA in vivo. The in vivo-generated viral RNA initiates limited replication of the vaccine virus, which in turn leads to efficient immunization. This technology allows the plasmid DNA to launch a live-attenuated vaccine in vitro or in vivo. Less than 10 ng of pTC83 iDNA encoding the full-length genomic RNA of the TC-83 vaccine strain initiated replication of the vaccine virus in vitro. In order to evaluate this approach in vivo, BALB/c mice were vaccinated with a single dose of pTC83 iDNA. After vaccination, all mice seroconverted with no adverse reactions. Four weeks after immunization, animals were challenged with the lethal epidemic strain of VEEV. All iDNA-vaccinated mice were protected from fatal disease, while all unvaccinated controls succumbed to infection and died. To our knowledge, this is the first example of launching a clinical live-attenuated vaccine from recombinant plasmid DNA in vivo.

  18. [Japanese Board Certified Thoracic Surgeon].

    PubMed

    Chihara, Koji

    2017-01-01

    The Japanese Board of General Thoracic Surgery (JBGTS) consisted by Japanese Association of Chest Surgery (JACS) and The Japanese Association of Thoracic Surgery (JATS) has been certified Japanese Board Certified Thoracic Surgeon (JBCTS) since 2004. At present, JBCTS is obtained by being of Certified Surgeon by Japan Surgical Society( JSS), completion of minimum requirement of surgical experience, scientific papers, presentation at medical assembly, learning of postgraduate educational programs, and examination approximate 11 years after graduation of medical school. Thirteen hundreds JBCTS throughout Japan are engaged in operation for 77,000 cases/year, including 38,000 lung cancer patients/year. The operative volume has been growing lineally these 30 years, and operative mortality in lung cancer patients has been less than 1% these several years. Japanese Medical Specialty Board (JMSB) published a guideline of the new system of medical specialty certification system in Jury 2014, in which fundamental structure is consisted by basic specialties of 19 medical fields and following subspecialties and program based system rather than curriculum based system. According to this guideline, JBGTS has been collaborated with JSS in order to establish sequential programs of the 2 specialties, and proposed an improved certification system to accomplish the mission that it educates trainees to be thoracic surgical professionals who is able to perform safe and standalized procedures.

  19. Color constancy in Japanese animation

    NASA Astrophysics Data System (ADS)

    Ichihara, Yasuyo G.

    2006-01-01

    In this study, we measure the colors used in a Japanese Animations. The result can be seen on CIE-xy color spaces. It clearly shows that the color system is not a natural appearance system but an imagined and artistic appearance system. Color constancy of human vision can tell the difference in skin and hair colors between under moonlight and day light. Human brain generates a match to the memorized color of an object from daylight viewing conditions to the color of the object in different viewing conditions. For example, Japanese people always perceive the color of the Rising Sun in the Japanese flag as red even in a different viewing condition such as under moonlight. Color images captured by a camera cannot present those human perceptions. However, Japanese colorists in Animation succeeded in painting the effects of color constancy not only under moonlight but also added the memory matching colors. They aim to create a greater impact on viewer's perceptions by using the effect of the memory matching colors. In this paper, we propose the Imagined Japanese Animation Color System. This system in art is currently a subject of research in Japan. Its importance is that it could also provide an explanation on how human brain perceives the same color under different viewing conditions.

  20. Recombinant Baculovirus Isolation.

    PubMed

    King, Linda A; Hitchman, Richard; Possee, Robert D

    2016-01-01

    Although there are several different methods available of making recombinant baculovirus expression vectors (reviewed in Chapter 3 ), all require a stage in which insect cells are transfected with either the virus genome alone (Bac-to-Bac(®) or BaculoDirect™, Invitrogen) or virus genome and transfer vector. In the latter case, this allows the natural process of homologous recombination to transfer the foreign gene, under control of the polyhedrin or other baculovirus gene promoter, from the transfer vector to the virus genome to create the recombinant virus. Previously, many methods required a plaque-assay to separate parental and recombinant virus prior to amplification and use of the recombinant virus. Fortunately, this step is no longer required for most systems currently available. This chapter provides an overview of the historical development of increasingly more efficient systems for the isolation of recombinant baculoviruses (Chapter 3 provides a full account of the different systems and transfer vectors available). The practical details cover: transfection of insect cells with either virus DNA or virus DNA and plasmid transfer vector; a reliable plaque-assay method that can be used to separate recombinant virus from parental (nonrecombinant) virus where this is necessary; methods for the small-scale amplification of recombinant virus; and subsequent titration by plaque-assay or real-time polymerase chain reaction (PCR). Methods unique to the Bac-to-Bac(®) system are also covered and include the transformation of bacterial cells and isolation of bacmid DNA ready for transfection of insect cells.

  1. Prevalence of metabolic syndrome compared between native Japanese and Japanese-Americans.

    PubMed

    Yoneda, Masayasu; Yamane, Kiminori; Jitsuiki, Kuniaki; Nakanishi, Shuhei; Kamei, Nozomu; Watanabe, Hiroshi; Kohno, Nobuoki

    2008-03-01

    Metabolic syndrome is a condition characterized by the accumulation of multiple risk factors for atherosclerosis. Japanese-Americans in the U.S. have a more rapid and intense progression of atherosclerosis than native Japanese in Japan due to a westernization of their lifestyle. We investigated the prevalence of metabolic syndrome between 416 native Japanese (194 men and 222 women) in Hiroshima and 574 Japanese-Americans (217 men and 357 women) in Los Angeles, aged 30-89 years. According to the criteria proposed by the Japanese Society of Internal Medicine, the prevalence was 13.9 and 2.7% for native Japanese men and women, and 32.7 and 3.4% for Japanese-American men and women, respectively. According to the IDF or AHA/NHLBI criteria, the prevalence was 20.1 and 6.3%, and 38.7 and 4.5%, or 13.4 and 14.4%, and 30.9 and 27.7%, respectively. Thus, the prevalence of metabolic syndrome in men was significantly higher in Japanese-American than in native Japanese by all the three criteria. However, the prevalence in women was similar between native Japanese and Japanese-American by the Japanese and IDF criteria, whereas it was significantly higher in Japanese-American than in native Japanese by the AHA/NHLBI criteria. This report demonstrates that a westernization of lifestyle can increase the prevalence of metabolic syndrome among Japanese-Americans as compared to native Japanese.

  2. Homogamy and Intermarriage of Japanese and Japanese Americans with Whites Surrounding World War II

    ERIC Educational Resources Information Center

    Ono, Hiromi; Berg, Justin

    2010-01-01

    Although some sociologists have suggested that Japanese Americans quickly assimilated into mainstream America, scholars of Japanese America have highlighted the heightened exclusion that the group experienced. This study tracked historical shifts in the exclusion level of Japanese and Japanese Americans in the United States surrounding World War…

  3. A Japanese Agenda for Management Development.

    ERIC Educational Resources Information Center

    Lim, Howard

    1982-01-01

    Discusses myths about the Japanese management styles; what the West can learn from the Japanese; the concept of nonlinear management; and training modules which teach self-discipline, tolerance, and nonlinear management. (CT)

  4. Japanese respond to campaign.

    PubMed

    1994-08-01

    A unique campaign launched by JOICFP in August 1993 had by the end of June 1994 netted US $41,200 to support activities of the integrated Project (IP) in developing countries. Under the campaign, the public, institutions, organizations, and businesses have been sending in used prepaid cards for sale to collectors in Japan and abroad. Prepaid cards are widely used throughout Japan for phones, subways, railways and highways. Nippon Telegraph and Telephone Corporation (NTT) alone issues 20 million cards annually. The campaign, which has been widely featured in the media, has proved effective for drawing attention to JOICFP and to population and family planning issues. Gaining the understanding of the Japanese public about population issues has grown in importance since the government's announcement of the new Global Issues Initiative (GII). Word about the campaign was carried by radio, television, newspapers, and magazines nationwide. The number of cards sent in escalated with the attention. By the end of June, JOICFP had received around 700,000 cards, of which 550,000 have been exchanged for cash. The funds generated by the card sales have been allocated to support grassroots IP activities and encourage the self-reliance of projects in China, Ghana, Guatemala, Nepal, Tanzania, and Zambia. Responses to the campaign have come from individuals as well as local governments, hospitals, enterprises, and educational institutions. Many of these have initiated their own card-collection system and information-dissemination activities to support JOICFP. Over 5000 different organizations are now collaborating with JOICFP for the campaign, including Tenmaya Department Store in Okayama City.

  5. HIV positive patient with HSV-2 encephalitis: case report.

    PubMed

    Pagliano, Pasquale; Ascione, Tiziana; Carleo, Maria Aurora; Boccia, Giovanni; De Caro, Francesco; Tortora, Fabio

    2016-09-01

    Incidence of brain infections in Human Immunodeficiency Virus (HIV) positive patients is reduced after the availability of current high active antiretroviral therapy (HAART). Herpes Simplex Virus type 2 (HSV-2) is an infrequent cause of encephalitis in HIV patients despite it is frequently involved in sexual transmitted infections. Here, we report a case of HSV-2 encephalitis occurring in a patient without full suppression of HIV replication within the brain. A 38 year-old HIV infected man was admitted to our department because of recurrent generalized seizure and fever during the previous 24 hours. Eight months before our observation the patient was switched from a protease inhibitor based regimen to a rilpivirine-based regimen without any evidence of HIV-RNA replication in the plasma. When the patient was admitted in our hospital, he was febrile and moderately confused, no deficit of cranial nerves was reported, motility was conserved, but he was unable to walk. Laboratory examinations performed at admission demonstrated an increase of cerebrospinal fluid (CSF) protein and cells with lymphocyte prevalence, and normal CSF glucose. HSV-2-DNA and HIV-RNA were present within CSF at admission. Nuclear Magnetic Resonance imaging of the brain revealed lesions of the medial part of both temporal lobes including hippocampus without any sign of bleeding. A 21-day course of acyclovir therapy was administered with consistent improvement of clinical findings and disappearance of HSV-2-DNA within CSF. After the episode, HAART was switched to a regimen with high CSF penetrability containing abacavir, lamivudine, darunavir and ritonavir. Twelve months after HSV-2 encephalitis neurologic evaluation was normal, but symptoms of depression were reported, HIV-RNA remained undetectable both in the plasma and CSF, and CD4+ lymphocytes were above 500/μL. No opportunistic infection was reported. Patients switched to regimen well tolerated such those containing rilpivirine, that have

  6. Three Views from Abroad: A Japanese Perspective.

    ERIC Educational Resources Information Center

    Nakadome, Takeaki

    1993-01-01

    Japanese school management should consider more broad-based, active participation in school board policymaking and should democratize school board-school relationships by adopting the lay-control principle. Both U.S. and Japanese schools should improve the exercise of appropriate administrator leadership. Japanese schools are evaluated on a…

  7. A Cultural Context for Japanese Education.

    ERIC Educational Resources Information Center

    Wojtan, Linda S.

    1985-01-01

    Certain Japanese educational practices serving as worthwhile examples to the United States' educational system are highlighted in this overview of Japanese education. However, it is stressed that because the United States and the Japanese educational systems are dependent upon their social context and exist in a symbiotic relationship within that…

  8. Persistence of Ethnicity: The Japanese of Colorado.

    ERIC Educational Resources Information Center

    Endo, Russell

    This paper presents an overview of the history of Japanese in Colorado. Japanese immigrants first came to Colorado between 1900 and 1910 as railroad laborers. Some became coal miners in southern Colorado; most others became farm laborers. Although the Japanese population during this period was small, communities developed in several locales. The…

  9. Schooling in Micronesia during Japanese Mandate Rule.

    ERIC Educational Resources Information Center

    Shuster, Donald R.

    1979-01-01

    This review of Japanese educational policy in Micronesia from 1920-36 describes the separate school systems established for natives and for Japanese immigrants. Native schools offered a shorter, less rigorous program whose main intent was socialization to Japanese language and culture. (SJL)

  10. The Work Values of Japanese Women.

    ERIC Educational Resources Information Center

    Engel, John W.

    Empirical studies of Japanese work ethics have tended to focus on male workers while neglecting women. In addition, work values in both Japan and the United States appear to be changing. More information is needed on the work values of American and Japanese female workers. A study was conducted to explore the work ethics of Japanese women and to…

  11. The Life Cycle of the Japanese Family.

    ERIC Educational Resources Information Center

    Kumagai, Fumie

    1984-01-01

    Analyzes the existing Japanese population data, focusing on changes in the timing of events in a family life cycle of Japanese women. Analysis revealed that the overall pattern of the family career of Japanese women today closely resembles that of their American and Canadian counterparts. (LLL)

  12. Generations and Identity: The Japanese American.

    ERIC Educational Resources Information Center

    Kitano, Harry H. L.

    The story of people of Japanese descent in the United States is told in its historic context. The Japanese came to America with cultural values that differed greatly from the mainstream U.S. society. They were also set apart by appearance. Conflict between Japan and the United States exacerbated the problems between the Japanese Americans and the…

  13. The Nonacademic Curriculum of the Japanese Preschool.

    ERIC Educational Resources Information Center

    Peach, Mark

    1994-01-01

    Japanese nursery school and kindergarten activities are designed to facilitate the socialization of Japanese children. The culture of the home and the culture of the school (and by extension the rest of Japanese society) are so different from each other that it is believed the open and unselfconscious help of the education system is necessary to…

  14. Shattering Myths: Japanese American Educational Issues.

    ERIC Educational Resources Information Center

    Yoshiwara, Florence M.

    An historical review of the immigration and resettlement patterns, and a demographic profile of Japanese Americans reveals a myth of the "successful minority." Since the founding of the Japanese American Citizens League in 1928, Japanese Americans have defeated alien land laws, discriminatory immigration quotas, anti-miscengenation laws,…

  15. A NEW CLASSIFICATION FOR THE JAPANESE VERB.

    ERIC Educational Resources Information Center

    TAKAHASHI, GEORGE

    JAPANESE VERBS AND THE PARTICLES WHICH OFTEN ACCOMPANY THEM PRESENT DIFFICULTIES TO LEARNERS OF THAT LANGUAGE. THE TRADITIONAL GRAMMATICAL TERMS, "TRANSITIVE" AND "INTRANSITIVE" (VERBS), REFLECT CONCEPTS WHICH ARE VALID IN ENGLISH BUT NOT IN JAPANESE. THE AUTHOR, IN ATTEMPTING TO CLASSIFY ALL JAPANESE VERBS ACCORDING TO THEIR…

  16. Developing Instructional Materials for Business Japanese.

    ERIC Educational Resources Information Center

    Koike, Shohei

    Business Japanese should be the study of Japanese language and culture for business communication and should include values and beliefs and institutional constraints on which the Japanese act as well as business etiquette and terminology. Topics to be covered in instruction will vary depending on the role (seller, buyer, or colleague) played by…

  17. JABEE in Japanese Engineering Education

    NASA Astrophysics Data System (ADS)

    Takeda, Kunihiko; Ishikawa, Tomoyuki

    JABEE in Japanese engineering education is discussed by focusing on the status and treatment of engineers in Japanese society and their achievements. The entrance fee and tuition of the engineering departments of higher education facilities are higher than those of the law, economy and literature departments. On the other hand, an engineer's lifelong wage is smaller than that of those who have graduated from the latter fields. Although engineering students must study for a longer period of time, the scholarship system to support these students in Japan falls far behind that in the U.S.A. The achievements of Japanese engineering were summarized from the viewpoint of economic indications such as 1) production of steel, 2) energy consumption per person as a function of GDP, 3) income 4) real estate abroad and miscellaneous factors such as the life spans and criminal rates of many countries. These analyses made it clear that Japanese engineers have the highest ability even compared to advanced countries and this is because of the higher engineering education in Japan ; but their status is unreasonably low in Japanese society. The four points by which the present status of Japanese engineers can be improved were discussed in relation to the introduction and the achievement of the JABEE system. The true aim of education reform by JABEE is that the engineering education in Japan should shift “from government to non-government”, “from organization to individual” and “from control to interdependency.” The expected points of improvement are discussed.

  18. Marine Biodiversity in Japanese Waters

    PubMed Central

    Fujikura, Katsunori; Lindsay, Dhugal; Kitazato, Hiroshi; Nishida, Shuhei; Shirayama, Yoshihisa

    2010-01-01

    To understand marine biodiversity in Japanese waters, we have compiled information on the marine biota in Japanese waters, including the number of described species (species richness), the history of marine biology research in Japan, the state of knowledge, the number of endemic species, the number of identified but undescribed species, the number of known introduced species, and the number of taxonomic experts and identification guides, with consideration of the general ocean environmental background, such as the physical and geological settings. A total of 33,629 species have been reported to occur in Japanese waters. The state of knowledge was extremely variable, with taxa containing many inconspicuous, smaller species tending to be less well known. The total number of identified but undescribed species was at least 121,913. The total number of described species combined with the number of identified but undescribed species reached 155,542. This is the best estimate of the total number of species in Japanese waters and indicates that more than 70% of Japan's marine biodiversity remains un-described. The number of species reported as introduced into Japanese waters was 39. This is the first attempt to estimate species richness for all marine species in Japanese waters. Although its marine biota can be considered relatively well known, at least within the Asian-Pacific region, considering the vast number of different marine environments such as coral reefs, ocean trenches, ice-bound waters, methane seeps, and hydrothermal vents, much work remains to be done. We expect global change to have a tremendous impact on marine biodiversity and ecosystems. Japan is in a particularly suitable geographic situation and has a lot of facilities for conducting marine science research. Japan has an important responsibility to contribute to our understanding of life in the oceans. PMID:20689840

  19. Postpartum Anti-N-methyl-D-aspartate Receptor Encephalitis: A Case Report and Literature Review

    PubMed Central

    Doden, Tadashi; Sekijima, Yoshiki; Ikeda, Junji; Ozawa, Kazuki; Ohashi, Nobuhiko; Kodaira, Minori; Hineno, Akiyo; Tachibana, Naoko; Ikeda, Shu-ichi

    2017-01-01

    We describe a 24-year-old woman with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis that developed 3 weeks after normal delivery. She was treated with methylprednisolone, intravenous immunoglobulin, and plasmapheresis, in addition to teratoma excision. However, her recovery was slow, and dysmnesia and mental juvenility persisted even two years after onset. To date, five patients with postpartum anti-NMDAR encephalitis have been reported. All of those patients showed psychotic symptoms and were suspected of having postpartum psychosis in the early period of the encephalitis. Changes in hormonal factors, modification of immune tolerance, or retrograde infection of the ovary may be contributing factors for postpartum anti-NMDAR encephalitis. PMID:28154283

  20. Anti-N-Methyl-D-Aspartate Receptor Encephalitis in HIV Infection

    PubMed Central

    Patarata, Eunice; Bernardino, Vera; Martins, Ana; Pereira, Rui; Loureiro, Conceição; Moraes-Fontes, Maria Francisca

    2016-01-01

    Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a rare condition characterized by emotional and behavioral disturbances, dyskinesias, and extrapyramidal signs. It occurs in young women of reproductive age and is classically described as a paraneoplastic phenomenon. We present a 36-year-old, HIV-positive female who was admitted to the hospital in an acute confusional state, with a stiff posture, periods of motor agitation, and myoclonic jerks of the hands. Her mental state progressively deteriorated. Without evidence of infection, the presence of anti-NMDAR antibodies both in serum and cerebrospinal fluid clinched the diagnosis of autoimmune encephalitis. No evidence of neoplastic disease was found, and the beneficial response to immunosuppressive therapy was exceptional. This is the first report of anti-NMDAR encephalitis in an HIV-infected individual, reminding us that autoimmune encephalitis should be included in the differential diagnosis of a young patient presenting in an acute confusional state. PMID:28101036