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Communications Biology Jan 2024Exposure to multiple mosquito-borne flaviviruses within a lifetime is not uncommon; however, how sequential exposures to different flaviviruses shape the cross-reactive...
Exposure to multiple mosquito-borne flaviviruses within a lifetime is not uncommon; however, how sequential exposures to different flaviviruses shape the cross-reactive humoral response against an antigen from a different serocomplex has yet to be explored. Here, we report that dengue-infected individuals initially primed with the Japanese encephalitis virus (JEV) showed broad, highly neutralizing potencies against Zika virus (ZIKV). We also identified a rare class of ZIKV-cross-reactive human monoclonal antibodies with increased somatic hypermutation and broad neutralization against multiple flaviviruses. One huMAb, K8b, binds quaternary epitopes with heavy and light chains separately interacting with overlapping envelope protein dimer units spanning domains I, II, and III through cryo-electron microscopy and structure-based mutagenesis. JEV virus-like particle immunization in mice further confirmed that such cross-reactive antibodies, mainly IgG3 isotype, can be induced and proliferate through heterologous dengue virus (DENV) serotype 2 virus-like particle stimulation. Our findings highlight the role of prior immunity in JEV and DENV in shaping the breadth of humoral response and provide insights for future vaccination strategies in flavivirus-endemic countries.
Topics: Humans; Animals; Mice; Encephalitis Virus, Japanese; Zika Virus; Zika Virus Infection; Cryoelectron Microscopy; Antibodies, Monoclonal; Dengue
PubMed: 38267569
DOI: 10.1038/s42003-023-05661-w -
Viruses Dec 2023Japanese encephalitis virus is a mosquito-borne member of the family. JEV is the leading cause of viral encephalitis in Asia and is characterized by encephalitis, high...
Japanese encephalitis virus is a mosquito-borne member of the family. JEV is the leading cause of viral encephalitis in Asia and is characterized by encephalitis, high lethality, and neurological sequelae in survivors. The virus also causes severe disease in swine, which are an amplifying host in the transmission cycle, and in horses. US agricultural authorities have recently recognized the threat to the swine industry and initiated preparedness activities. Other mosquito-borne viruses exotic to the Western Hemisphere have been introduced and established in recent years, including West Nile, Zika, and chikungunya viruses, and JEV has recently invaded continental Australia for the first time. These events amply illustrate the potential threat of JEV to US health security. Susceptible indigenous mosquito vectors, birds, feral and domestic pigs, and possibly bats, constitute the receptive ecological ingredients for the spread of JEV in the US. Fortunately, unlike the other virus invaders mentioned above, an inactivated whole virus JE vaccine (IXIARO) has been approved by the US Food and Drug Administration for human use in advance of a public health emergency, but there is no veterinary vaccine. This paper describes the risks and potential consequences of the introduction of JEV into the US, the need to integrate planning for such an event in public health policy, and the requirement for additional countermeasures, including antiviral drugs and an improved single dose vaccine that elicits durable immunity in both humans and livestock.
Topics: Humans; United States; Animals; Horses; Swine; Encephalitis, Japanese; Encephalitis Virus, Japanese; Encephalitis, Viral; Agriculture; Chiroptera; Culicidae; Vaccines; Zika Virus; Zika Virus Infection
PubMed: 38257754
DOI: 10.3390/v16010054 -
Pathogens (Basel, Switzerland) Dec 2023Pigs are important animals for meat production but can carry several zoonotic diseases, including the Japanese encephalitis virus, Nipah virus, and influenza viruses....
Pigs are important animals for meat production but can carry several zoonotic diseases, including the Japanese encephalitis virus, Nipah virus, and influenza viruses. Several and respiratory viruses require cleavage of envelope proteins to acquire viral infectivity and consequently, need a host protease or the addition of exogenous trypsin for efficient propagation. Host TMPRSS2 is a key protease responsible for viral cleavage. Stable expression of human TMPRSS2 in African green monkey-derived Vero cells can enhance the porcine epidemic diarrhea virus. However, considering the narrow host tropism of viruses, a porcine cell line expressing pig TMPRSS2 could be optimal for replicating pig-derived viruses. Herein, we generated and evaluated a pig-derived PK-15 cell line stably expressing pig TMPRSS2. This cell line markedly (>1000-fold) and specifically enhanced the growth of influenza viruses. Furthermore, we demonstrated the usefulness of a PK-15 cell line lacking the gene with a stable expression of pig TMPRSS2 for efficient virus isolation from clinical samples in the presence of type I interferons. Therefore, PK-15 cells expressing pig TMPRSS2 could be a valuable and promising tool for virus isolation, vaccine production, and virological studies of TMPRSS2-dependent viruses.
PubMed: 38251326
DOI: 10.3390/pathogens13010018 -
Frontiers in Microbiology 2023Japanese encephalitis is one of the most important insect-borne infectious disease with public health concern. The virus can break the blood-brain barrier and cause...
Japanese encephalitis is one of the most important insect-borne infectious disease with public health concern. The virus can break the blood-brain barrier and cause death or long-term sequela in infected humans or animals. Viral encephalitis is an important clinical feature of JEV infection. In recent studies, CircRNAs and related ceRNAs data illustrated the regulative role in many aspects of biological process and disease duration. It is believed that CircRNA regulates JEV infection in a ceRNA-dependent mechanism. In this study, brain tissues of experimental mice were sequenced and analysised. 61 differentially expressed circRNAs, 172 differentially expressed miRNAs and 706 differentially expressed mRNAs were identified by RNA-Sequencing and statistical analysis. CX3CR1 was determined as a key host factor impact JEV infection by microRNA interference measurement. CX3CR1 interaction network indicated circStrbp/miR709/CX3CR1 as a functional regulation axis. Further sequencing in BV2 cell shown CX3CR1 is a special target of miR-709 only during JEV infection. In summary, our study presented a new ceRNA pathway that impact JEV infection and , which could be a therapeutic target to fight against JEV.
PubMed: 38249464
DOI: 10.3389/fmicb.2023.1165378 -
Virology Journal Jan 2024N6-methyladenosine (m6A) is present in diverse viral RNA and plays important regulatory roles in virus replication and host antiviral innate immunity. However, the role...
N6-methyladenosine (m6A) is present in diverse viral RNA and plays important regulatory roles in virus replication and host antiviral innate immunity. However, the role of m6A in regulating JEV replication has not been investigated. Here, we show that the JEV genome contains m6A modification upon infection of mouse neuroblast cells (neuro2a). JEV infection results in a decrease in the expression of m6A writer METTL3 in mouse brain tissue. METTL3 knockdown by siRNA leads to a substantial decrease in JEV replication and the production of progeny viruses at 48 hpi. Mechanically, JEV triggered a considerable increase in the innate immune response of METTL3 knockdown neuro2a cells compared to the control cells. Our study has revealed the distinctive m6A signatures of both the virus and host in neuro2a cells infected with JEV, illustrating the positive role of m6A modification in JEV infection. Our study further enhances understanding of the role of m6A modification in Flaviviridae viruses.
Topics: Animals; Mice; Encephalitis Virus, Japanese; Methyltransferases; RNA, Small Interfering; Immunity, Innate; Virus Replication; Encephalitis, Japanese
PubMed: 38243270
DOI: 10.1186/s12985-023-02275-w -
BMC Infectious Diseases Jan 2024Predictive models for vector-borne diseases (VBDs) are instrumental to understanding the potential geographic spread of VBDs and therefore serve as useful tools for...
Predictive models for vector-borne diseases (VBDs) are instrumental to understanding the potential geographic spread of VBDs and therefore serve as useful tools for public health decision-making. However, predicting the emergence of VBDs at the micro-, local, and regional levels presents challenges, as the importance of risk factors can vary spatially and temporally depending on climatic factors and vector and host abundance and preferences. We propose an expert-systems-based approach that uses an analytical hierarchy process (AHP) deployed within a geographic information system (GIS), to predict areas susceptible to the risk of Japanese encephalitis virus (JEV) emergence. This modelling approach produces risk maps, identifying micro-level risk areas with the potential for disease emergence. The results revealed that climatic conditions, especially the minimum temperature and precipitation required for JEV transmission, contributed to high-risk conditions developed during January and March of 2022 in Victora. Compared to historical climate records, the risk of JEV emergence was increased in most parts of the state due to climate. Importantly, the model accurately predicted 7 out of the 8 local government areas that reported JEV-positive cases during the outbreak of 2022 in Victorian piggeries. This underscores the model's potential as a reliable tool for supporting local risk assessments in the face of evolving climate change.
Topics: Humans; Victoria; Encephalitis Virus, Japanese; Climate Change; Disease Outbreaks; Systems Analysis
PubMed: 38191322
DOI: 10.1186/s12879-023-08741-8 -
Cureus Dec 2023Dengue and Japanese encephalitis (JE) are diseases that often conquer the top headlines in the leading newspapers during epidemics. Although recovery is the rule in most...
Dengue and Japanese encephalitis (JE) are diseases that often conquer the top headlines in the leading newspapers during epidemics. Although recovery is the rule in most dengue cases, some unfortunately land up with multiple organ dysfunction syndromes, get critical, and even succumb to death. The main risk here is bleeding due to thrombocytopenia and platelet dysfunction. On the other hand, JE often presents with acute encephalitis syndrome (AES). We report a confirmed case of dengue (NS1 reactive, IgM dengue positive) by enzyme-linked immunosorbent assay (ELISA) who developed sudden onset altered sensorium. Non-contrast computed tomography (NCCT) head was done, which showed an infarct in the right gangliocapsular region with normal-sized ventricles. The patient had deteriorated in the past four days, which warranted a repeat NCCT head, revealing dilated ventricles and hemorrhagic transformation in the old infarct with surrounding edema. CSF viral markers were suggestive of IgM anti-JE virus positive. An MRI brain was planned but could not be done due to the deteriorating condition of the patient. Unfortunately, the patient landed up with multiple organ dysfunction syndrome and succumbed to death.
PubMed: 38186422
DOI: 10.7759/cureus.50146 -
Journal of Clinical Neurology (Seoul,... Jan 2024Acute infectious encephalitis is a widely studied clinical syndrome. Although identified almost 100 years ago, its immediate and delayed consequences are still neglected... (Review)
Review
Acute infectious encephalitis is a widely studied clinical syndrome. Although identified almost 100 years ago, its immediate and delayed consequences are still neglected despite their high frequency and possible severity. We reviewed the available data on sequelae and persisting symptoms following infectious encephalitis with the aim of characterizing the clinical picture of these patients at months to years after hospitalization. We searched PubMed for case series involving sequelae after infectious encephalitis. We carried out a narrative review of the literature on encephalitis caused by members of the family (herpes simplex virus, varicella zoster virus, and human herpesvirus-6), members of the family (West Nile virus, tick-borne encephalitis virus, and Japanese encephalitis virus), alphaviruses, and Nipah virus. We retrieved 41 studies that yielded original data involving 3,072 adult patients evaluated after infectious encephalitis. At least one of the five domains of cognitive outcome, psychiatric disorders, neurological deficits, global functioning, and quality of life was investigated in the reviewed studies. Various tests were used in the 41 studies and the investigation took place at different times after hospital discharge. The results showed that most patients are discharged with impairments, with frequent deficits in cognitive function such as memory loss or attention disorders. Sequelae tend to improve within several years following flavivirus or Nipah virus infection, but long-term data are scarce for other pathogens. Further research is needed to better understand the extent of sequelae after infectious encephalitis, and to propose a standardized assessment method and assess the rehabilitation efficacy in these patients.
PubMed: 38179629
DOI: 10.3988/jcn.2023.0240 -
Frontiers in Cellular and Infection... 2023Japanese encephalitis (JE) is a naturally occurring localized disease caused by the Japanese encephalitis virus, which is spread by the Culex tritaeniorhynchus. China...
Japanese encephalitis (JE) is a naturally occurring localized disease caused by the Japanese encephalitis virus, which is spread by the Culex tritaeniorhynchus. China has a high rate of JE. Shanxi, located in North China, has a high prevalence of adult JE. Adult JE has more severe complications, mortality, and a higher disease burden, making it a public health issue. This retrospective study examined the dynamic epidemic changes, high-risk areas of JE, and clinical characteristics and prognostic factors of adult JE in Shanxi Province. The findings revealed that July to September was the primary epidemic season of JE and that JE cases were mainly in individuals over the age of 40. The incidence of JE from 2005 to 2022 demonstrated a positive spatial correlation with significant clustering characteristics, with high-incidence clusters in the south and southeast. Multivariate logistic regression analysis revealed that higher cerebrospinal fluid pressure, higher white blood cell counts, higher neutrophil percentage, deep coma, and lower albumin were independent factors for poor prognosis of adult JE. The developed risk prediction model holds great promise in early prognosis assessment of patients, providing a basis for clinical decision-making and early clinical intervention.
Topics: Adult; Humans; Encephalitis, Japanese; Prognosis; Retrospective Studies; China
PubMed: 38179427
DOI: 10.3389/fcimb.2023.1291816 -
Frontiers in Neurology 2023Japanese encephalitis (JE) is a severe infectious disease affecting the central nervous system (CNS). However, limited risk factors have been identified for predicting...
Japanese encephalitis (JE) is a severe infectious disease affecting the central nervous system (CNS). However, limited risk factors have been identified for predicting poor prognosis (PP) in adults with severe JE. In this study, we analyzed clinical data from thirty-eight severe adult JE patients and compared them to thirty-three patients without organic CNS disease. Machine learning techniques employing branch-and-bound algorithms were used to identify clinical risk factors. Based on clinical outcomes, patients were categorized into two groups: the PP group (mRs ≥ 3) and the good prognosis (GP) group (mRs ≤ 2) at three months post-discharge. We found that the neutrophil-to-lymphocyte ratio (NLR) and the percentage of neutrophilic count (N%) were significantly higher in the PP group compared to the GP group. Conversely, the percentage of lymphocyte count (L%) was significantly lower in the PP group. Additionally, elevated levels of aspartate aminotransferase (AST) and blood glucose were observed in the PP group compared to the GP group. The clinical parameters most strongly correlated with prognosis, as indicated by Pearson correlation coefficient (PCC), were NLR (PCC 0.45) and blood glucose (PCC 0.45). In summary, our findings indicate that increased serum NLR, N%, decreased L%, abnormal glucose metabolism, and liver function impairment are risk factors associated with poor prognosis in severe adult JE patients.
PubMed: 38178886
DOI: 10.3389/fneur.2023.1242317