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Japanese Encephalitis Virus: The Emergence of Genotype IV in Australia and Its Potential Endemicity.Viruses Nov 2022A fatal case of Japanese encephalitis (JE) occurred in northern Australia in early 2021. Sequence studies showed that the virus belonged to genotype IV (GIV), a genotype... (Review)
Review
A fatal case of Japanese encephalitis (JE) occurred in northern Australia in early 2021. Sequence studies showed that the virus belonged to genotype IV (GIV), a genotype previously believed to be restricted to the Indonesian archipelago. This was the first locally acquired case of Japanese encephalitis virus (JEV) GIV to occur outside Indonesia, and the second confirmed fatal human case caused by a GIV virus. A closely related GIV JEV strain subsequently caused a widespread outbreak in eastern Australia in 2022 that was first detected by fetal death and abnormalities in commercial piggeries. Forty-two human cases also occurred with seven fatalities. This has been the first major outbreak of JEV in mainland Australia, and geographically the largest virgin soil outbreak recorded for JEV. This outbreak provides an opportunity to discuss and document the factors involved in the virus' spread and its ecology in a novel ecological milieu in which other flaviviruses, including members of the JE serological complex, also occur. The probable vertebrate hosts and mosquito vectors are discussed with respect to virus spread and its possible endemicity in Australia, and the need to develop a One Health approach to develop improved surveillance methods to rapidly detect future outbreak activity across a large geographical area containing a sparse human population. Understanding the spread of JEV in a novel ecological environment is relevant to the possible threat that JEV may pose in the future to other receptive geographic areas, such as the west coast of the United States, southern Europe or Africa.
Topics: Animals; Humans; Encephalitis Virus, Japanese; Encephalitis, Japanese; Genotype; Mosquito Vectors; Vertebrates; Culex
PubMed: 36366578
DOI: 10.3390/v14112480 -
Pharmacological Reports : PR Apr 2022Japanese encephalitis (JE) caused by the Japanese encephalitis virus (JEV) is one of Asia's most common viral encephalitis. JEV is a flavivirus, common in rural and... (Review)
Review
Japanese encephalitis (JE) caused by the Japanese encephalitis virus (JEV) is one of Asia's most common viral encephalitis. JEV is a flavivirus, common in rural and sub-urban regions of Asian countries. Although only 1% of JEV-infected individuals develop JE, there is a 20-30% chance of death among these individuals and possible neurological sequelae post-infection. No licensed anti-JE drugs are currently available, despite extensive efforts to develop them. Literature search was performed using databases such as PubMed Central, Google Scholar, Wiley Online Library, etc. using keywords such as Japanese encephalitis virus, antiviral drugs, antiviral drug screening, antiviral drug targets, etc. From around 230 papers/abstracts and research reviews retrieved and reviewed for this study, approximately 180 most relevant and important ones have been cited. Different approaches in drug testing and various antiviral drug targets explored so far have been thoroughly searched from the literature and compiled, besides addressing the future perspectives of the antiviral drug development strategies. Although the development of effective anti-JE drugs is an urgent issue, only supportive care is currently available. Recent advancements in understanding the biology of infection and new drug targets have been promising improvements. Despite hindrances such as the unavailability of a proper drug delivery system or a treatment regimen irrespective of the stage of infection, several promising anti-JE candidate molecules are in different phases of clinical trials. Nonetheless, efficient therapy against JEV is expected to be achieved with drug combinations and a highly targeted drug delivery system soon.
Topics: Antiviral Agents; Drug Evaluation, Preclinical; Encephalitis Virus, Japanese; Encephalitis, Japanese; Humans
PubMed: 35182390
DOI: 10.1007/s43440-022-00355-2 -
Viruses Oct 2022In the last three decades, several flaviviruses of concern that belong to different antigenic groups have expanded geographically. This has resulted in the presence of... (Review)
Review
In the last three decades, several flaviviruses of concern that belong to different antigenic groups have expanded geographically. This has resulted in the presence of often more than one virus from a single antigenic group in some areas, while in Europe, Africa and Australia, additionally, multiple viruses belonging to the Japanese encephalitis (JE) serogroup co-circulate. Morphological heterogeneity of flaviviruses dictates antibody recognition and affects virus neutralization, which influences infection control. The latter is further impacted by sequential infections involving diverse flaviviruses co-circulating within a region and their cross-reactivity. The ensuing complex molecular virus-host interplay leads to either cross-protection or disease enhancement; however, the molecular determinants and mechanisms driving these outcomes are unclear. In this review, we provide an overview of the epidemiology of four JE serocomplex viruses, parameters affecting flaviviral heterogeneity and antibody recognition, host immune responses and the current knowledge of the cross-reactivity involving JE serocomplex flaviviruses that leads to differential clinical outcomes, which may inform future preventative and therapeutic interventions.
Topics: Humans; Encephalitis Viruses, Japanese; Encephalitis, Japanese; Flavivirus; Cross Reactions; Europe; Encephalitis Virus, Japanese; Antibodies, Viral; West Nile virus
PubMed: 36298768
DOI: 10.3390/v14102213 -
Viruses Jul 2023Japanese encephalitis virus (JEV), a mosquito-borne zoonotic virus, is one of the most important causes of human viral encephalitis. JEV relies on various attachment or...
Japanese encephalitis virus (JEV), a mosquito-borne zoonotic virus, is one of the most important causes of human viral encephalitis. JEV relies on various attachment or entry co-factors to enter host cells. Among these co-factors, hTIM-1 has been identified as an attachment factor to promote JEV infection through interacting with phosphatidylserine (PS) on the viral envelope. However, the reasons why JEV prefers to use hTIM-1 over other PS binding receptors are unknown. Here, we demonstrated that hTIM-1 can directly interact with JEV E protein. The interaction between hTIM-1 and JEV relies on specific binding sites, respectively, ND114115 in the hTIM-1 IgV domain and K38 of the E protein. Furthermore, during the early stage of infection, hTIM-1 and JEV are co-internalized into cells and transported into early and late endosomes. Additionally, we found that the hTIM-1 soluble ectodomain protein effectively inhibits JEV infection in vitro. Moreover, hTIM-1-specific antibodies have been shown to downregulate JEV infectivity in cells. Taken together, these findings suggested that hTIM-1 protein directly interacts with JEV E protein and mediates JEV infection, in addition to the PS-TIM-1 interaction.
Topics: Animals; Humans; Encephalitis Virus, Japanese; Encephalitis, Japanese; Viral Envelope Proteins
PubMed: 37515282
DOI: 10.3390/v15071589 -
Journal of Microbiology and... Aug 2022Japanese encephalitis (JE) is a vaccine-preventable mosquito-borne disease caused by infection with the Japanese encephalitis virus (JEV). JEV has five genotypes,... (Review)
Review
Japanese encephalitis (JE) is a vaccine-preventable mosquito-borne disease caused by infection with the Japanese encephalitis virus (JEV). JEV has five genotypes, including genotype V (GV), which is considered ancestral to the other genotypes. The first GV strain, GV Muar, was isolated from a Malayan patient in 1952 and GV did not reappear for 57 years until GV XZ0934 was isolated from a mosquito sample in China. Since 2010, 21 GV strains have been identified in Republic of Korea (ROK). Both GV Muar and GV XZ0934 are more pathogenic than other GI/GIII strains and are serologically distinct. However, because the ROK's GV strains have not been experimentally tested, their characteristics are not known. Characterization of the ROK's isolates is needed to enable development of effective GV strain-based vaccines to protect against GV infections.
Topics: Animals; China; Culicidae; Encephalitis Virus, Japanese; Encephalitis, Japanese; Genotype; Humans
PubMed: 35879275
DOI: 10.4014/jmb.2207.07002 -
Vaccines Nov 2023Japanese encephalitis (JE) remains the cause of vaccine-preventable encephalitis in individuals living in endemic areas and international travelers. Although rare, the... (Review)
Review
Japanese encephalitis (JE) remains the cause of vaccine-preventable encephalitis in individuals living in endemic areas and international travelers. Although rare, the disease's high fatality rate emphasizes the need for effective immunization. This review aims to provide updated data on the JE burden between 2017 and 2023, vaccine acceptance, and vaccine strategies for travelers. We prospectively identified studies, using MEDLINE and PubMed, published through 2023. JE incidence has decreased in local populations and remains low among travelers from non-endemic countries. The local JE risk cannot be utilized to determine traveler risk. Adult travelers naïve to JEV infection or immunization may be at potentially higher risk. The JE vaccine acceptance rates among international travelers visiting JE endemic areas range from 0.2% to 28.5%. The cost of the vaccine and low risk perception could be barriers to JE vaccination. For travelers, an accelerated two-dose regimen of inactivated Vero cell JE vaccine (JE-VC) or a single dosage of live attenuated JE vaccine (JE-LV) may be an option. In conclusion, the JE burden among residents and travelers is lower, but the risk is not negligible. Practitioners should prioritize sharing knowledge, increasing awareness, and promoting vaccinations and preventive measures to reduce tourists' risk of JE along their journey.
PubMed: 38006016
DOI: 10.3390/vaccines11111683 -
Journal of Vector Borne Diseases 2022Japanese encephalitis (JE) is a very serious public health problem in India and the conducive environment permit its emergence in non-endemic areas in the country. There... (Review)
Review
Japanese encephalitis (JE) is a very serious public health problem in India and the conducive environment permit its emergence in non-endemic areas in the country. There are constant changes taking place in the pattern of current agricultural practices and vector breeding habitats which had far-reaching consequences on the epidemiology of JE and the severity of epidemic outbreaks today. Due to the continuous ecological changes taking place, vectors changed in their breeding dynamics, feeding, and resting behavior and started invading previously non-endemic areas. JE has recently spread to new territories due to land-use changes, including forest fragmentation and concentrated livestock production. Changes in the livestock population decreased the cattle pig ratio which enhanced the Japanese encephalitis virus (JEV) infection. This review brings forth the present widespread changes encountered that grossly impact the risk of infection in many places for the emergence of Japanese encephalitis and to address the implications for its control.
Topics: Animals; Swine; Cattle; Encephalitis, Japanese; Seasons; Encephalitis Virus, Japanese; India; Disease Outbreaks
PubMed: 36751762
DOI: 10.4103/0972-9062.345180 -
Functional & Integrative Genomics May 2023Vector-borne diseases are serious public health concern. Mosquito is one of the major vectors responsible for the transmission of a number of diseases like malaria,... (Review)
Review
Vector-borne diseases are serious public health concern. Mosquito is one of the major vectors responsible for the transmission of a number of diseases like malaria, Zika, chikungunya, dengue, West Nile fever, Japanese encephalitis, St. Louis encephalitis, and yellow fever. Various strategies have been used for mosquito control, but the breeding potential of mosquitoes is such tremendous that most of the strategies failed to control the mosquito population. In 2020, outbreaks of dengue, yellow fever, and Japanese encephalitis have occurred worldwide. Continuous insecticide use resulted in strong resistance and disturbed the ecosystem. RNA interference is one of the strategies opted for mosquito control. There are a number of mosquito genes whose inhibition affected mosquito survival and reproduction. Such kind of genes could be used as bioinsecticides for vector control without disturbing the natural ecosystem. Several studies have targeted mosquito genes at different developmental stages by the RNAi mechanism and result in vector control. In the present review, we included RNAi studies conducted for vector control by targeting mosquito genes at different developmental stages using different delivery methods. The review could help the researcher to find out novel genes of mosquitoes for vector control.
Topics: Animals; Humans; Yellow Fever; RNA Interference; Ecosystem; Mosquito Control; Zika Virus Infection; Dengue; Zika Virus; Aedes; Culex
PubMed: 37227504
DOI: 10.1007/s10142-023-01072-6 -
International Journal of Molecular... Oct 2022Flaviviruses (the genus of the family) include many arthropod-borne viruses, often causing life-threatening diseases in humans, such as hemorrhaging and encephalitis.... (Review)
Review
Flaviviruses (the genus of the family) include many arthropod-borne viruses, often causing life-threatening diseases in humans, such as hemorrhaging and encephalitis. Although the flaviviruses have a significant clinical impact, it has become apparent that flavivirus replication is restricted by cellular factors induced by the interferon (IFN) response, which are called IFN-stimulated genes (ISGs). SHFL (shiftless antiviral inhibitor of ribosomal frameshifting) is a novel ISG that inhibits dengue virus (DENV), West Nile virus (WNV), Zika virus (ZIKV), and Japanese encephalitis virus (JEV) infections. Interestingly, SHFL functions as a broad-spectrum antiviral factor exhibiting suppressive activity against various types of RNA and DNA viruses. In this review, we summarize the current understanding of the molecular mechanisms by which SHFL inhibits flavivirus infection and discuss the molecular basis of the inhibitory mechanism using a predicted tertiary structure of SHFL generated by the program AlphaFold2.
Topics: Humans; Flavivirus; Interferons; Zika Virus; Zika Virus Infection; Antiviral Agents; Encephalitis Virus, Japanese; Encephalitis, Japanese; RNA; Virus Replication
PubMed: 36293480
DOI: 10.3390/ijms232012619 -
PLoS Neglected Tropical Diseases May 2022Japanese Encephalitis (JE) is known for its high case fatality ratio (CFR) and long-term neurological sequelae. Over the years, efforts in JE treatment and control might...
BACKGROUND
Japanese Encephalitis (JE) is known for its high case fatality ratio (CFR) and long-term neurological sequelae. Over the years, efforts in JE treatment and control might change the JE fatality risk. However, previous estimates were from 10 years ago, using data from cases in the 10 years before this. Estimating JE disease severity is challenging because data come from countries with different JE surveillance systems, diagnostic methods, and study designs. Without precise and timely JE disease severity estimates, there is continued uncertainty about the JE disease burden and the effect of JE vaccination.
METHODOLOGY
We performed a systematic review to collate age-stratified JE fatality and morbidity data. We used a stepwise model selection with BIC as the selection criteria to identify JE CFR drivers. We used stacked regression, to predict country-specific JE CFR from 1961 to 2030. JE morbidity estimates were grouped from similar study designs to estimate the proportion of JE survivors with long-term neurological sequelae.
PRINCIPAL FINDINGS
We included 82 and 50 peer-reviewed journal articles published as of March 06 2021 for JE fatality and morbidity with 22 articles in both analyses. Results suggested overall JE CFR estimates of 26% (95% CI 22, 30) in 1961-1979, 20% (95% CI 17, 24) in 1980-1999, 14% (95% CI 11, 17) in 2000-2018, and 14% (95% CI 11, 17) in 2019-2030. Holding other variables constant, we found that JE fatality risk decreased over time (OR: 0.965; 95% CI: 0.947-0.983). Younger JE cases had a slightly higher JE fatality risk (OR: 1.012; 95% CI: 1.003-1.021). The odds of JE fatality in countries with JE vaccination is 0.802 (90% CI: 0.653-0.994; 95% CI: 0.62-1.033) times lower than the odds in countries without JE vaccination. Ten percentage increase in the percentage of rural population to the total population was associated with 15.35% (95% CI: 7.71, 22.57) decrease in JE fatality odds. Ten percentage increase in population growth rate is associated with 3.71% (90% CI: 0.23, 7.18; 95% CI: -0.4, 8.15) increase in JE fatality odds. Adjusting for the effect of year, rural population percent, age of JE cases, and population growth rate, we estimated that there was a higher odds of JE fatality in India compared to China. (OR: 5.46, 95% CI: 3.61-8.31). Using the prediction model we found that, in 2000-2018, Brunei, Pakistan, and Timor-Leste were predicted to have the highest JE CFR of 20%. Bangladesh, Guam, Pakistan, Philippines, and Vietnam had projected JE CFR over 20% for after 2018, whereas the projected JE CFRs were below 10% in China, Indonesia, Cambodia, Myanmar, Malaysia, and Thailand. For disability, we estimated that 36% (min-max 0-85) JE patients recovered fully at hospital discharge. One year after hospital discharge, 46% (min-max 0%-97%) JE survivors were estimated to live normally but 49% (min-max 3% - 86%)till had neurological sequelae.
CONCLUSION
JE CFR estimates were lower than 20% after 2000. Our study provides an updated estimation of CFR and proportion of JE cases with long-term neurological sequelae that could help to refine cost-benefit assessment for JE control and elimination programs.
Topics: China; Encephalitis, Japanese; Humans; Japanese Encephalitis Vaccines; Morbidity; Philippines; Thailand
PubMed: 35613183
DOI: 10.1371/journal.pntd.0010361