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Viruses Jun 2021Japanese encephalitis virus (JEV) is a zoonotic pathogen mainly found in East and Southeast Asia and transmitted by mosquitoes. The objective of this review is to... (Meta-Analysis)
Meta-Analysis Review
Japanese encephalitis virus (JEV) is a zoonotic pathogen mainly found in East and Southeast Asia and transmitted by mosquitoes. The objective of this review is to summarize the knowledge on the diversity of JEV mosquito vector species. Therefore, we systematically analyzed reports of JEV found in field-caught mosquitoes as well as experimental vector competence studies. Based on the investigated publications, we classified 14 species as confirmed vectors for JEV due to their documented experimental vector competence and evidence of JEV found in wild mosquitoes. Additionally, we identified 11 mosquito species, belonging to five genera, with an experimentally confirmed vector competence for JEV but lacking evidence on their JEV transmission capacity from field-caught mosquitoes. Our study highlights the diversity of confirmed and potential JEV vector species. We also emphasize the variety in the study design of vector competence investigations. To account for the diversity of the vector species and regional circumstances, JEV vector competence should be studied in the local context, using local mosquitoes with local virus strains under local climate conditions to achieve reliable data. In addition, harmonization of the design of vector competence experiments would lead to better comparable data, informing vector and disease control measures.
Topics: Animals; Disease Vectors; Encephalitis Virus, Japanese; Encephalitis, Japanese; Geography, Medical; Global Health; Humans; Mosquito Vectors; Population Surveillance
PubMed: 34208737
DOI: 10.3390/v13061154 -
Viruses Feb 2023Japanese encephalitis virus (JEV) is an arboviral, encephalitogenic, zoonotic flavivirus characterized by its complex epidemiology whose transmission cycle involves...
Japanese encephalitis virus (JEV) is an arboviral, encephalitogenic, zoonotic flavivirus characterized by its complex epidemiology whose transmission cycle involves reservoir and amplifying hosts, competent vector species and optimal environmental conditions. Although typically endemic in Asia and parts of the Pacific Islands, unprecedented outbreaks in both humans and domestic pigs in southeastern Australia emphasize the virus' expanding geographical range. To estimate areas at highest risk of JEV transmission in Australia, ecological niche models of vectors and waterbirds, a sample of piggery coordinates and feral pig population density models were combined using mathematical and geospatial mapping techniques. These results highlight that both coastal and inland regions across the continent are estimated to have varying risks of enzootic and/or epidemic JEV transmission. We recommend increased surveillance of waterbirds, feral pigs and mosquito populations in areas where domestic pigs and human populations are present.
Topics: Humans; Animals; Encephalitis, Japanese; Mosquito Vectors; Encephalitis Virus, Japanese; Epidemics; Encephalitis Viruses, Japanese; Australia
PubMed: 36851664
DOI: 10.3390/v15020450 -
Microbiology Spectrum Jun 2022Quick and accurate detection of neutralizing antibodies (nAbs) against yellow fever is essential in serodiagnosis during outbreaks for surveillance and to evaluate...
Quick and accurate detection of neutralizing antibodies (nAbs) against yellow fever is essential in serodiagnosis during outbreaks for surveillance and to evaluate vaccine efficacy in population-wide studies. All of this requires serological assays that can process a large number of samples in a highly standardized format. Albeit being laborious, time-consuming, and limited in throughput, the classical plaque reduction neutralization test (PRNT) is still considered the gold standard for the detection and quantification of nAbs due to its sensitivity and specificity. Here, we report the development of an alternative fluorescence-based serological assay (SNT) with an equally high sensitivity and specificity that is fit for high-throughput testing with the potential for automation. Finally, our novel SNT was cross-validated in several reference laboratories and against international WHO standards, showing its potential to be implemented in clinical use. SNT assays with similar performance are available for the Japanese encephalitis, Zika, and dengue viruses amenable to differential diagnostics. Fast and accurate detection of neutralizing antibodies (nAbs) against yellow fever virus (YFV) is key in yellow fever serodiagnosis, outbreak surveillance, and monitoring of vaccine efficacy. Although classical PRNT remains the gold standard for measuring YFV nAbs, this methodology suffers from inherent limitations such as low throughput and overall high labor intensity. We present a novel fluorescence-based serum neutralization test (SNT) with equally high sensitivity and specificity that is fit for processing a large number of samples in a highly standardized manner and has the potential to be implemented for clinical use. In addition, we present SNT assays with similar performance for Japanese encephalitis, Zika, and dengue viruses, opening new avenues for differential diagnostics.
Topics: Antibodies, Neutralizing; Antibodies, Viral; Encephalitis, Japanese; Humans; Neutralization Tests; Yellow Fever; Yellow fever virus; Zika Virus; Zika Virus Infection
PubMed: 35670599
DOI: 10.1128/spectrum.02548-21 -
Frontiers in Microbiology 2023Japanese encephalitis (JE) is a zoonotic ailment from the Japanese encephalitis virus (JEV). JEV belongs to the flavivirus genus and is categorized into a solitary... (Review)
Review
Japanese encephalitis (JE) is a zoonotic ailment from the Japanese encephalitis virus (JEV). JEV belongs to the flavivirus genus and is categorized into a solitary serotype consisting of five genetically diverse genotypes (I, II, III, IV, and V). The JEV genotype III (GIII) was the prevailing strain responsible for multiple outbreaks in countries endemic to JEV until 1990. In recent years, significant improvements have occurred in the epidemiology of JE, encompassing the geographical expansion of the epidemic zone and the displacement of prevailing genotypes. The dominant genotype of the JEV has undergone a progressive shift from GIII to GI due to variations in its adaptability within avian populations. From 2021 to 2022, Australia encountered an epidemic of viral encephalitis resulting from infection with the GIV JEV pathogen. The current human viral encephalitis caused by GIV JEV is the initial outbreak since its initial discovery in Indonesia during the late 1970s. Furthermore, following a time frame of 50 years, the detection and isolation of GV JEV have been reported in mosquitoes across China and South Korea. Evidence suggests that the prevalence of GIV and GV JEV epidemic regions may be on the rise, posing a significant threat to public safety and the sustainable growth of animal husbandry. The global approach to preventing and managing JE predominantly revolves around utilizing the GIII strain vaccine for vaccination purposes. Nevertheless, research has demonstrated that the antibodies generated by the GIII strain vaccine exhibit limited capacity to neutralize the GI and GV strains. Consequently, these antibodies cannot protect against JEV challenge caused by animal GI and GV strains. The limited cross-protective and neutralizing effects observed between various genotypes may be attributed to the low homology of the E protein with other genotypes. In addition, due to the GIV JEV outbreak in Australia, further experiments are needed to evaluate the protective efficiency of the current GIII based JE vaccine against GIV JEV. The alteration of the prevailing genotype of JEV and the subsequent enlargement of the geographical extent of the epidemic have presented novel obstacles in JE prevention and control. This paper examines the emerging features of the JE epidemic in recent years and the associated problems concerning prevention and control.
PubMed: 38045034
DOI: 10.3389/fmicb.2023.1302101 -
Archives of Virology Sep 2022Japanese encephalitis virus (JEV), a single-stranded, enveloped RNA virus, is a health concern across Asian countries, associated with severe neurological disorders,... (Review)
Review
Japanese encephalitis virus (JEV), a single-stranded, enveloped RNA virus, is a health concern across Asian countries, associated with severe neurological disorders, especially in children. Primarily, pigs, bats, and birds are the natural hosts for JEV, but humans are infected incidentally. JEV requires a few host proteins for its entry and replication inside the mammalian host cell. The endoplasmic reticulum (ER) plays a significant role in JEV genome replication and assembly. During this process, the ER undergoes stress due to its remodelling and accumulation of viral particles and unfolded proteins, leading to an unfolded protein response (UPR). Here, we review the overall strategy used by JEV to infect the host cell and various cytopathic effects caused by JEV infection. We also highlight the role of JEV structural proteins (SPs) and non-structural proteins (NSPs) at various stages of the JEV life cycle that are involved in up- and downregulation of different host proteins and are potentially relevant for developing efficient therapeutic drugs.
Topics: Animals; Cell Line; Child; Encephalitis Virus, Japanese; Encephalitis, Japanese; Humans; Mammals; Swine; Unfolded Protein Response; Virus Replication
PubMed: 35654913
DOI: 10.1007/s00705-022-05481-z -
Acta Neurologica Belgica Apr 2022
Topics: Antibodies, Viral; COVID-19; COVID-19 Vaccines; Encephalitis; Encephalitis, Japanese; Humans
PubMed: 35182374
DOI: 10.1007/s13760-022-01898-0 -
Pathology Oct 2022The unprecedented emergence of Japanese encephalitis (JE) in mainland Australia represents an outbreak of high clinical and public health significance. JE is a zoonosis... (Review)
Review
The unprecedented emergence of Japanese encephalitis (JE) in mainland Australia represents an outbreak of high clinical and public health significance. JE is a zoonosis spread by mosquitoes and is one of the most important causes of endemic viral encephalitis in South-East Asia and the Indian subcontinent. While occasional cases of human Japanese encephalitis virus (JEV) infection have occurred in far north Australia, its detection in pigs and the substantial number of locally acquired human cases across multiple jurisdictions in early 2022 prompted the declaration of this outbreak as a Communicable Disease Incident of National Significance. Laboratory testing for JEV is complex, and most cases are diagnosed by serology, for which interpretation is difficult. This review provides a comprehensive outline of currently available methods for JEV diagnosis including serology, nucleic acid amplification testing, virus isolation, sequencing and metagenomics. The relative advantages and disadvantages of the diagnostic tests are presented, as well as their value in clinical and public health contexts. This review also explores the role of mosquito, veterinary and human surveillance as part of the laboratory response to JEV. As JEV may become endemic in Australia, a collaborative and coordinated One Health approach involving animal, human and environmental health is required for optimal disease response and control.
Topics: Animals; Culicidae; Encephalitis Virus, Japanese; Encephalitis, Japanese; Humans; Nucleic Acids; Swine; Zoonoses
PubMed: 35995617
DOI: 10.1016/j.pathol.2022.07.001 -
H3K27me3 of Rnf19a promotes neuroinflammatory response during Japanese encephalitis virus infection.Journal of Neuroinflammation Jul 2023Histone methylation is an important epigenetic modification that affects various biological processes, including the inflammatory response. In this study, we found that...
Histone methylation is an important epigenetic modification that affects various biological processes, including the inflammatory response. In this study, we found that infection with Japanese encephalitis virus (JEV) leads to an increase in H3K27me3 in BV2 microglial cell line, primary mouse microglia and mouse brain. Inhibition of H3K27me3 modification through EZH2 knockdown and treatment with EZH2 inhibitor significantly reduces the production of pro-inflammatory cytokines during JEV infection, which suggests that H3K27me3 modification plays a crucial role in the neuroinflammatory response caused by JEV infection. The chromatin immunoprecipitation-sequencing (ChIP-sequencing) assay revealed an increase in H3K27me3 modification of E3 ubiquitin ligases Rnf19a following JEV infection, which leads to downregulation of Rnf19a expression. Furthermore, the results showed that Rnf19a negatively regulates the neuroinflammatory response induced by JEV. This is achieved through the degradation of RIG-I by mediating its ubiquitination. In conclusion, our findings reveal a novel mechanism by which JEV triggers extensive neuroinflammation from an epigenetic perspective.
Topics: Animals; Mice; Encephalitis Virus, Japanese; Histones; Encephalitis, Japanese; Inflammation; Encephalitis Viruses, Japanese; Ubiquitin-Protein Ligases
PubMed: 37480121
DOI: 10.1186/s12974-023-02852-4 -
Viruses Feb 2023Japanese encephalitis virus (JEV), which uses a mosquito primary vector and swine as a reservoir host, poses a significant risk to human and animal health. JEV can be...
Japanese encephalitis virus (JEV), which uses a mosquito primary vector and swine as a reservoir host, poses a significant risk to human and animal health. JEV can be detected in cattle, goats and dogs. A molecular epidemiological survey of JEV was conducted in 3105 mammals from five species, swine, fox, racoon dog, yak and goat, and 17,300 mosquitoes from 11 Chinese provinces. JEV was detected in pigs from Heilongjiang (12/328, 3.66%), Jilin (17/642, 2.65%), Shandong (14/832, 1.68%), Guangxi (8/278, 2.88%) and Inner Mongolia (9/952, 0.94%); in goats (1/51, 1.96%) from Tibet; and mosquitoes (6/131, 4.58%) from Yunnan. A total of 13 JEV envelope (E) gene sequences were amplified in pigs from Heilongjiang (5/13), Jilin (2/13) and Guangxi (6/13). Swine had the highest JEV infection rate of any animal species, and the highest infection rates were found in Heilongjiang. Phylogenetic analysis indicated that the predominant strain in Northern China was genotype I. Mutations were found at residues 76, 95, 123, 138, 244, 474 and 475 of E protein but all sequences had predicted glycosylation sites at 'N154. Three strains lacked the threonine 76 phosphorylation site from non-specific (unsp) and protein kinase G (PKG) site predictions; one lacked the threonine 186 phosphorylation site from protein kinase II (CKII) prediction; and one lacked the tyrosine 90 phosphorylation site from epidermal growth factor receptor (EGFR) prediction. The aim of the current study was to contribute to JEV prevention and control through the characterization of its molecular epidemiology and prediction of functional changes due to E-protein mutations.
Topics: Cattle; Animals; Humans; Swine; Dogs; Encephalitis Virus, Japanese; Phylogeny; China; Genotype; Encephalitis Viruses, Japanese; Encephalitis, Japanese; Culicidae; Threonine; Mammals
PubMed: 36992334
DOI: 10.3390/v15030625 -
Cell Reports Sep 2023Japanese encephalitis (JE) is a vector-borne viral disease that causes acute encephalitis in children. Although vaccines have been developed against the JE virus (JEV),...
Japanese encephalitis (JE) is a vector-borne viral disease that causes acute encephalitis in children. Although vaccines have been developed against the JE virus (JEV), no effective antiviral therapy exists. Our study shows that inhibition of poly(ADP-ribose) polymerase 1 (PARP1), an NAD-dependent (poly-ADP) ribosyl transferase, protects against JEV infection. Interestingly, PARP1 is critical for JEV pathogenesis in Neuro-2a cells and mice. Small molecular inhibitors of PARP1, olaparib, and 3-aminobenzamide (3-AB) significantly reduce clinical signs and viral load in the serum and brains of mice and improve survival. PARP1 inhibition confers protection against JEV infection by inhibiting autophagy. Mechanistically, upon JEV infection, PARP1 PARylates AKT and negatively affects its phosphorylation. In addition, PARP1 transcriptionally upregulates PTEN, the PIP3 phosphatase, negatively regulating AKT. PARP1-mediated AKT inactivation promotes autophagy and JEV pathogenesis by increasing the FoxO activity. Thus, our findings demonstrate PARP1 as a potential mediator of JEV pathogenesis that can be effectively targeted for treating JE.
Topics: Child; Humans; Encephalitis, Japanese; Encephalitis Virus, Japanese; Proto-Oncogene Proteins c-akt; Brain; Poly (ADP-Ribose) Polymerase-1
PubMed: 37676769
DOI: 10.1016/j.celrep.2023.113103