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Frontiers in Cellular and Infection... 2022The genus Flavivirus of the family includes important viruses, such as Dengue, Zika, West Nile, Japanese encephalitis, Murray Valley encephalitis, tick-borne... (Review)
Review
The genus Flavivirus of the family includes important viruses, such as Dengue, Zika, West Nile, Japanese encephalitis, Murray Valley encephalitis, tick-borne encephalitis, Yellow fever, Saint Louis encephalitis, and Usutu viruses. They are transmitted by mosquitoes or ticks, and they can infect humans, causing fever, encephalitis, or haemorrhagic fever. The treatment resources for these diseases and the number of vaccines available are limited. It has been discovered that eukaryotic cells synthesize small RNA molecules that can bind specifically to sequences present in messenger RNAs to inhibit the translation process, thus regulating gene expression. These small RNAs have been named microRNAs, and they have an important impact on viral infections. In this review, we compiled the available information on miRNAs that can interact with the 3' untranslated region (3'UTR) of the flavivirus genome, a conserved region that is important for viral replication and translation.
Topics: Animals; Humans; 3' Untranslated Regions; MicroRNAs; Computational Biology; Flavivirus; Encephalitis, Japanese; Zika Virus; Zika Virus Infection
PubMed: 36310869
DOI: 10.3389/fcimb.2022.976843 -
IJID Regions Sep 2022The aim of this study was to investigate the presence of Japanese encephalitis virus (JEV) in a rice-farming community in the Philippines and to determine its...
OBJECTIVES
The aim of this study was to investigate the presence of Japanese encephalitis virus (JEV) in a rice-farming community in the Philippines and to determine its implications regarding the epidemiology of viral encephalitides in the Asia-Pacific Region.
METHODS
Mosquitoes were collected monthly from animal-baited traps close to flooded rice fields in two barangays (villages) in the Municipality of San Jose, Tarlac Province in Luzon, from May 2009 to July 2010. Virus was detected by nested reverse transcription PCR. Phylogenetic analysis of the amplified virus envelope gene was done using the maximum-likelihood method.
RESULTS
A total of 28 700 known vector mosquitoes were collected, namely , and . JEV genotype III was detected in , belonging to the same genotype but form a different clade from those reported in the 1980s and in 2020 in this country.
CONCLUSIONS
Japanese encephalitis is associated with rice cultivation and the presence of infected mosquitoes in Tarlac, Philippines. It remains to be seen whether the observed genetic shift of genotype III to genotype I in Asia will in time have an impact on the epidemiology of Japanese encephalitis in the Philippines. For long-term disease control, regular surveillance and Japanese encephalitis immunization in children and travelers in high risk areas are recommended.
PubMed: 36093364
DOI: 10.1016/j.ijregi.2022.05.005 -
Archives of Virology Mar 2022Japanese encephalitis (JE) is a zoonotic epidemic disease caused by Japanese encephalitis virus (JEV), and currently, no medicines are available to treat this disease....
Japanese encephalitis (JE) is a zoonotic epidemic disease caused by Japanese encephalitis virus (JEV), and currently, no medicines are available to treat this disease. Autophagy modulators play an important role in the treatment of tumors, heart disease, and some viral diseases. The aim of this study was to investigate the effects of autophagy modulators on JEV infection and the host response in mice. The experimental mice were grouped as follows: DMEM (control), JEV, JEV+rapamycin (JEV+Rapa), JEV+wortmannin (JEV+Wort), JEV+chloroquine (JEV+CQ), Rapa, Wort, and CQ. The control group was treated with DMEM. The mice in other groups were infected with 10 PFU of JEV, and Rapa, Wort, and CQ were administered 2 h prior to JEV challenge and then administered daily for 10 consecutive days. All mice were monitored for neurological signs and survival. The damage of subcellular structures in the mouse brain was evaluated by transmission electron microscopy. The distribution of virus in the mouse brain was determined by RNAScope staining and immunohistochemical staining. The neuroinflammatory responses in the brain were examined via quantitative real-time PCR, and the signal pathways involved in neuroinflammation were identified by Western blot. The mice in the JEV+Wort and JEV+CQ groups showed milder neurological symptoms, less damage to the mitochondria in the brain tissue, and a higher survival rate than those in the JEV+Rapa and JEV groups. Compared with the JEV+Rapa and JEV groups, the distribution of JEV in the brain of mice in the JEV+Wort and JEV+CQ groups was lower, and the inflammatory response was weaker. No significant difference was observed in the expression of the PI3K/AKT/NF-κB pathway in mouse brain among the different groups. Our study suggests that the autophagy inhibitors Wort and CQ reduce JEV infection and weaken the inflammatory response, which does not depend on the PI3K/AKT/NF-κB pathway in mouse brain.
Topics: Animals; Autophagy; Encephalitis Virus, Japanese; Encephalitis, Japanese; Inflammation; Mice; Phosphatidylinositol 3-Kinases
PubMed: 35119507
DOI: 10.1007/s00705-021-05283-9 -
Pathogens (Basel, Switzerland) May 2022Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, is the leading cause of pediatric encephalitis in Southeast Asia. The enzootic transmission of JEV... (Review)
Review
Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, is the leading cause of pediatric encephalitis in Southeast Asia. The enzootic transmission of JEV involves two types of amplifying hosts, swine and avian species. The involvement of pigs in the transmission cycle makes JEV a unique pathogen because human Japanese encephalitis cases are frequently linked to the epizootic spillover from pigs, which can not only develop viremia to sustain transmission but also signs of neurotropic and reproductive disease. The existing knowledge of the epidemiology of JEV largely suggests that viremic pigs are a source of infectious viruses for competent mosquito species, especially in the endemic regions. However, several recently published studies that applied molecular detection techniques to the characterization of JEV pathogenesis in pigs described the shedding of JEV through multiple routes and persistent infection, both of which have not been reported in the past. These findings warrant a re-examination of the role that pigs are playing in the transmission and maintenance of JEV. In this review, we summarize discoveries on the shedding of JEV during the course of infection and analyze the available published evidence to discuss the possible role of the vector-free JEV transmission route among pigs in viral maintenance.
PubMed: 35631096
DOI: 10.3390/pathogens11050575 -
Viruses May 2023Japanese encephalitis virus (JEV) is a member of the Flaviviridae family and one of Asia's most common causes of encephalitis. JEV is a zoonotic virus that is...
Japanese encephalitis virus (JEV) is a member of the Flaviviridae family and one of Asia's most common causes of encephalitis. JEV is a zoonotic virus that is transmitted to humans through the bite of infected mosquitoes of the species. While humans are dead-end hosts for the virus, domestic animals such as pigs and birds are amplification hosts. Although JEV naturally infected monkeys have been reported in Asia, the role of non-human primates (NHPs) in the JEV transmission cycle has not been intensively investigated. In this study, we demonstrated neutralizing antibodies against JEV in NHPs () and humans living in proximity in two provinces located in western and eastern Thailand by using Plaque Reduction Neutralization Test (PRNT). We found a 14.7% and 5.6% seropositive rate in monkeys and 43.7% and 45.2% seropositive rate in humans living in west and east Thailand, respectively. This study observed a higher seropositivity rate in the older age group in humans. The presence of JEV neutralizing antibodies in NHPs that live in proximity to humans shows the occurrence of natural JEV infection, suggesting the endemic transmission of this virus in NHPs. According to the One Health concept, regular serological studies should be conducted especially at the animal-human interface.
Topics: Humans; Animals; Swine; Aged; Encephalitis Virus, Japanese; Thailand; Haplorhini; Encephalitis, Japanese; Antibodies, Neutralizing; Antibodies, Viral
PubMed: 37243211
DOI: 10.3390/v15051125 -
Seizure Jul 2022We aimed to study seizure characteristics during the acute phase of Japanese encephalitis (JE) in children, determine the risk factors of postencephalitic epilepsy...
BACKGROUND
We aimed to study seizure characteristics during the acute phase of Japanese encephalitis (JE) in children, determine the risk factors of postencephalitic epilepsy (PEE), establish a risk prediction model for the disease, and construct a nomogram to visualize the model.
METHODS
We retrospectively analyzed the clinical data and follow-up results of 328 children with JE who were hospitalized between January 2011 and December 2020. Risk factors were screened using univariable analysis, a predictive model was built using binary logistic analysis, lasso regression was used for variable screening, and a nomogram was developed.
RESULTS
Of the 328 children with JE enrolled in the study, 216 (65.9%, 216/328) had seizures in the acute phase. The incidence of PEE was 14.7% (39/264), The cumulative percentages of PEE after discharge was 10.6% (28/264)at 6 months, which increased to 13.6%(36/264)at 3 years. 38.5% of patients with PEE had generalized onset seizures, and 17.9% had focal motor seizures. Univariable analysis revealed that 22 clinical indicators were related to the PPE; Multivariable analysis identified seizure number >5 (OR (95%CI) = 3.013 (1.046-8.676), P = 0.041), status epilepticus (OR (95%CI) = 3.918 (1.212-12.669), P = 0.023), and Coma (OR (95%CI) = 22.495 (8.686-58.285), P<0.001) as independent risk factors for PEE. The risk prediction model: ln(p/1p)= -3.533 + 1.103 × (seizures number > 5) +1.366 × (status epilepticus) + 3.113 × (Coma) was developed, and a nomogram was constructed. The area under the ROC curve (AUC), calibration plot, and Hosmer-Lemeshow test showed that the model had good discrimination and calibration. Ordinary bootstrapping was used for internal validation, and the predictive results of the original and test sets were consistent.
CONCLUSIONS
Seizure is a common manifestation during acute encephalitis and sequelae in children with JE. The nomogram constructed in this study could be used for early prediction, and could facilitate early intervention.
Topics: Child; Coma; Encephalitis, Japanese; Epilepsy; Humans; Retrospective Studies; Risk Factors; Seizures; Status Epilepticus
PubMed: 35636157
DOI: 10.1016/j.seizure.2022.05.017 -
Infection Ecology & Epidemiology 2019Vietnam is a tropical country where mosquito-borne diseases are common. This review explores the transmission of mosquito-borne flaviviruses in urban areas of... (Review)
Review
Vietnam is a tropical country where mosquito-borne diseases are common. This review explores the transmission of mosquito-borne flaviviruses in urban areas of Vietnam. It concludes that urban transmission has mainly been studied for Dengue virus, and so far, much less for Japanese encephalitis virus. Dengue is the most common flavivirus in Vietnam. Due to fast urbanization and favorable climatic conditions, the viral transmission concentrates mainly to large cities with high population density including Ha Noi, Nha Trang and Ho Chi Minh. Human cases of Japanese encephalitis have been controlled by an expanded immunization program. However, this virus is still circulating throughout the country, also in cities due to the pig rearing practices in urban and peri-urban areas. Zika virus is an additional major concern because it has long circulated in the Northern area and is now increasingly diagnosed in urban areas of the Central, Central Highlands and Southern regions using the same mosquito vectors as Dengue virus. There was alarge outbreak of Zika disease from 2016 to early 2017, with most infections observed in Ho Chi Minh city, the largest town in Vietnam. Other flaviviruses circulate in Vietnam but have not been investigated in terms of urban transmission.
PubMed: 31528273
DOI: 10.1080/20008686.2019.1660129 -
Viruses Jan 2023Genotype IV Japanese encephalitis (JE) virus (GIV JEV) is the least common and most neglected genotype in JEV. We evaluated the growth and pathogenic potential of the...
Genotype IV Japanese encephalitis (JE) virus (GIV JEV) is the least common and most neglected genotype in JEV. We evaluated the growth and pathogenic potential of the GIV strain 19CxBa-83-Cv, which was isolated from a mosquito pool in Bali, Indonesia, in 2019, and serological analyses were also conducted. The growth ability of 19CxBa-83-Cv in Vero cells was intermediate between that of the genotype I (GI) strain Mie/41/2002 and the genotype V (GV) strain Muar, whereas 19CxBa-83-Cv and Mie/41/2002 grew faster than Muar in mouse neuroblastoma cells. The neuroinvasiveness of 19CxBa-83-Cv in mice was higher than that of Mie/41/2002 but lower than that of Muar; however, there were no significant differences in neurovirulence in mice among the three strains. The neutralizing titers of sera from 19CxBa-83-Cv- and Mie/41/2002-inoculated mice against 19CxBa-83-Cv and Mie/41/2002 were similar, whereas the titers against Muar were lower than those of the other two viruses. The neutralizing titers of JE vaccine-inoculated mouse pool serum against 19CxBa-83-Cv and Muar were significantly lower than those against Mie/41/2002. The neutralizing titers against the three viruses were similar in three out of the five serum samples from GI-infected JE patients, although the titers against Mie/41/2002 were higher than those against 19CxBa-83-Cv and Muar in the remaining two sera samples. In summary, we identified the basic characteristics of 19CxBa-83-Cv, but further studies are needed to better understand GIV JEV.
Topics: Chlorocebus aethiops; Animals; Mice; Encephalitis Virus, Japanese; Encephalitis, Japanese; Antibodies, Neutralizing; Vero Cells; Antibodies, Viral; Encephalitis Viruses, Japanese; Genotype
PubMed: 36680278
DOI: 10.3390/v15010239 -
Journal of Virology Jul 2023Powassan virus (POWV) is an emerging tick-borne flavivirus that causes neuroinvasive diseases, including encephalitis, meningitis, and paralysis. Similar to other...
Powassan virus (POWV) is an emerging tick-borne flavivirus that causes neuroinvasive diseases, including encephalitis, meningitis, and paralysis. Similar to other neuroinvasive flaviviruses, such as West Nile virus (WNV) and Japanese encephalitis virus (JEV), POWV disease presentation is heterogeneous, and the factors influencing disease outcome are not fully understood. We used Collaborative Cross (CC) mice to assess the impact of host genetic factors on POWV pathogenesis. We infected a panel of -null CC lines with POWV and observed a range of susceptibility, indicating that host factors other than the well-characterized flavivirus restriction factor modulate POWV pathogenesis in CC mice. Among the -null CC lines, we identified multiple highly susceptible lines (0% survival), including CC071 and CC015, and two resistant lines, CC045 and CC057 (>75% survival). The susceptibility phenotypes generally were concordant among neuroinvasive flaviviruses, although we did identify one line, CC006, that was specifically resistant to JEV, suggesting that both pan-flavivirus and virus-specific mechanisms contribute to susceptibility phenotypes in CC mice. We found that POWV replication was restricted in bone marrow-derived macrophages from CC045 and CC057 mice, suggesting that resistance could result from cell-intrinsic restriction of viral replication. Although serum viral loads at 2 days postinfection were equivalent between resistant and susceptible CC lines, clearance of POWV from the serum was significantly enhanced in CC045 mice. Furthermore, CC045 mice had significantly lower viral loads in the brain at 7 days postinfection than did CC071 mice, suggesting that reduced central nervous system (CNS) infection contributes to the resistant phenotype of CC045 mice. Neuroinvasive flaviviruses, such as WNV, JEV, and POWV, are transmitted to humans by mosquitoes or ticks and can cause neurologic diseases, such as encephalitis, meningitis, and paralysis, and they can result in death or long-term sequelae. Although potentially severe, neuroinvasive disease is a rare outcome of flavivirus infection. The factors that determine whether someone develops severe disease after a flavivirus infection are not fully understood, but host genetic differences in polymorphic antiviral response genes likely contribute to the outcome of infection. We evaluated a panel of genetically diverse mice and identified lines with distinct outcomes following infection with POWV. We found that resistance to POWV pathogenesis corresponded to reduced viral replication in macrophages, more rapid clearance of virus in peripheral tissues, and reduced viral infection in the brain. These susceptible and resistant mouse lines will provide a system for investigating the pathogenic mechanisms of POWV and identifying polymorphic host genes that contribute to resistance.
Topics: Humans; Mice; Animals; Flavivirus; Collaborative Cross Mice; Flavivirus Infections; West Nile virus; Encephalitis Viruses, Tick-Borne; Encephalitis Virus, Japanese; Encephalitis; Disease Susceptibility; Paralysis; 2',5'-Oligoadenylate Synthetase
PubMed: 37310228
DOI: 10.1128/jvi.00715-23 -
Journal of Acute Medicine Sep 2022Japanese encephalitis (JE) is critical epidemic encephalitis caused by the JE virus (JEV) in Southeast Asia. The World Health Organization defined "acute encephalitis...
Japanese encephalitis (JE) is critical epidemic encephalitis caused by the JE virus (JEV) in Southeast Asia. The World Health Organization defined "acute encephalitis syndrome" (AES) as an acute onset of fever with a change of mental status and/or new-onset seizure, mainly for the surveillance of JE. The key clues for the diagnosis include the patient age group of unvaccinated era or waning vaccine-induced immunity and the history of possible mosquito bites in epidemic areas. We report a 47-year old man who is in an unvaccinated era with potential waning immunity. The patient presented with fever and altered mental status for 2 days. He was speechless and could not follow commands. The patient had gone camping in the countryside a week before the visit. At the emergency department, neck stiffness was noted. There was a leukocytosis with a left shift by blood cell count. The brain computed tomography was essentially normal. The cerebrospinal fluid (CSF) sample via lumbar puncture showed leukocytosis, a high protein level, and a low sugar level in comparison to serum tests. Further antibody test of CSF confirmed the diagnosis. Magnetic resonance imaging (MRI) of the brain revealed a high signal in the right thalamus and a mildly swollen left caudate nucleus 4 days after admission. He was extubated and finally discharged with partial dependency on activities of daily living. This case reminds us of the JE in AES. Emergency physicians should be aware of the suspicious case of unvaccinated age or waning immunity and possible mosquito bites in epidemic areas. The role of MRI on JE was also discussed in this article.
PubMed: 36313605
DOI: 10.6705/j.jacme.202209_12(3).0005