-
Journal of Neuroinflammation Mar 2024Japanese encephalitis virus (JEV) is a neurotropic pathogen that causes lethal encephalitis. The high susceptibility and massive proliferation of JEV in neurons lead to...
Japanese encephalitis virus (JEV) is a neurotropic pathogen that causes lethal encephalitis. The high susceptibility and massive proliferation of JEV in neurons lead to extensive neuronal damage and inflammation within the central nervous system. Despite extensive research on JEV pathogenesis, the effect of JEV on the cellular composition and viral tropism towards distinct neuronal subtypes in the brain is still not well comprehended. To address these issues, we performed single-cell RNA sequencing (scRNA-seq) on cells isolated from the JEV-highly infected regions of mouse brain. We obtained 88,000 single cells and identified 34 clusters representing 10 major cell types. The scRNA-seq results revealed an increasing amount of activated microglia cells and infiltrating immune cells, including monocytes & macrophages, T cells, and natural killer cells, which were associated with the severity of symptoms. Additionally, we observed enhanced communication between individual cells and significant ligand-receptor pairs related to tight junctions, chemokines and antigen-presenting molecules upon JEV infection, suggesting an upregulation of endothelial permeability, inflammation and antiviral response. Moreover, we identified that Baiap2-positive neurons were highly susceptible to JEV. Our findings provide valuable clues for understanding the mechanism of JEV induced neuro-damage and inflammation as well as developing therapies for Japanese encephalitis.
Topics: Mice; Animals; Encephalitis Virus, Japanese; Viral Tropism; Central Nervous System; Encephalitis Viruses, Japanese; Encephalitis, Japanese; Inflammation; Sequence Analysis, RNA
PubMed: 38532383
DOI: 10.1186/s12974-024-03071-1 -
Journal of Virology Apr 2024Dengue vaccine candidates have been shown to improve vaccine safety and efficacy by altering the residues or accessibility of the fusion loop on the virus envelope...
UNLABELLED
Dengue vaccine candidates have been shown to improve vaccine safety and efficacy by altering the residues or accessibility of the fusion loop on the virus envelope protein domain II (DII) in an animal study. The current study aimed to comprehensively investigate the impact of DII mutations on the antigenicity, immunogenicity, and protective efficacy of Japanese encephalitis virus (JEV) virus-like particles (VLPs) in mice. We found the DII G106K/L107D (KD) and W101G/G106K/L107D (GKD) mutations altered the binding activity of JEV VLP to cross-reactive monoclonal antibodies but had no effect on their ability to elicit total IgG antibodies in mice. However, JEV VLPs with KD or GKD mutations induced significantly less neutralizing antibodies against JEV. Only 46% and 31% of the KD and GKD VLPs-immunized mice survived compared to 100% of the wild-type (WT) VLP-immunized mice after a lethal JEV challenge. In passive protection experiments, naïve mice that received sera from WT VLP-immunized mice exhibited a significantly higher survival rate of 46.7% compared to those receiving sera from KD VLP- and GKD VLP-immunized mice (6.7% and 0%, respectively). This study demonstrated that JEV DII is crucial for eliciting potently neutralizing antibodies and protective immunity against JEV.
IMPORTANCE
Introduction of mutations into the fusion loop is one potential strategy for generating safe dengue and Zika vaccines by reducing the risk of severe dengue following subsequent infections, and for constructing live-attenuated vaccine candidates against newly emerging Japanese encephalitis virus (JEV) or Japanese encephalitis (JE) serocomplex virus. The monoclonal antibody studies indicated the fusion loop of JE serocomplex viruses primarily comprised non-neutralizing epitopes. However, the present study demonstrates that the JEV fusion loop plays a critical role in eliciting protective immunity in mice. Modifications to the fusion loop of JE serocomplex viruses might negatively affect vaccine efficacy compared to dengue and zika serocomplex viruses. Further studies are required to assess the impact of mutant fusion loop encoded by commonly used JEV vaccine strains on vaccine efficacy or safety after subsequent dengue virus infection.
Topics: Animals; Mice; Amino Acids; Antibodies, Neutralizing; Antibodies, Viral; Dengue; Encephalitis Virus, Japanese; Encephalitis, Japanese; Epitopes; Japanese Encephalitis Vaccines; Viral Envelope Proteins; Zika Virus; Zika Virus Infection
PubMed: 38530012
DOI: 10.1128/jvi.01773-23 -
Cureus Mar 2024Introduction The administration of routine vaccinations to patients following hematopoietic stem cell transplantation (HSCT) is highly recommended. However, studies...
Introduction The administration of routine vaccinations to patients following hematopoietic stem cell transplantation (HSCT) is highly recommended. However, studies examining reasons for not completing vaccination in post-HSCT patients are lacking. Method We reviewed the medical records of patients who sought vaccination following HSCT from January 2012 to December 2018 at the Center for Infectious Diseases, Nara Medical University. Results Information regarding patients' backgrounds, administered vaccines, and reasons for not administering recommended vaccines was collected for the study. Thirty-five patients (22 men and 13 women) with a median time from HSCT to the first visit of 25 months were enrolled. Vaccine coverage was highest for diphtheria, tetanus, and acellular pertussis (DTaP) at 89% (31 patients), followed by 23-valent pneumococcal, measles/rubella/mumps, and Japanese encephalitis at 71% (25 patients), 71% (25 patients), and 63% (22 persons), respectively. However, vaccine coverage for hepatitis B, 13-valent pneumococcal, and Hib was low at 26% (three patients), 11% (four patients), and 40% (14 patients), respectively. The reason for not completing the recommended vaccination series was not provided for most cases; however, the economic barrier was cited for all vaccines. Discussion This study identified several cases in Japan where individuals stopped completing post-HSCT vaccinations due to financial constraints. Larger-scale studies may be necessary in Japan in the future for further investigation.
PubMed: 38528999
DOI: 10.7759/cureus.56842 -
Frontiers in Veterinary Science 2024Japanese encephalitis virus (JEV), a member of the Flaviviridae family and a flavivirus, is known to induce acute encephalitis. Vimentin protein has been identified as a...
Japanese encephalitis virus (JEV), a member of the Flaviviridae family and a flavivirus, is known to induce acute encephalitis. Vimentin protein has been identified as a potential receptor for JEV, engaging in interactions with the viral membrane protein. The Fc fragment, an integral constituent of immunoglobulins, plays a crucial role in antigen recognition by dendritic cells (DCs) or phagocytes, leading to subsequent antigen presentation, cytotoxicity, or phagocytosis. In this study, we fused the receptor of JEV vimentin with the Fc fragment of IgG and expressed the resulting vimentin-Fc fusion protein in . Pull-down experiments demonstrated the binding ability of the vimentin-Fc fusion protein to JEV virion . Additionally, we conducted inhibition assays at the cellular level, revealing the ability of vimentin-Fc protein suppressing JEV replication, it may be a promising passive immunotherapy agent for JEV. These findings pave the way for potential therapeutic strategies against JEV.
PubMed: 38500602
DOI: 10.3389/fvets.2024.1368725 -
JMIR Public Health and Surveillance Mar 2024Live attenuated vaccines may be used to prevent nontargeted diseases such as lower respiratory tract infections (LRTIs) due to their nonspecific effects (NSEs).
Investigating Nonspecific Effects of the Live-Attenuated Japanese Encephalitis Vaccine on Lower Respiratory Tract Infections in Children Aged 25-35 Months: Retrospective Cohort Study.
BACKGROUND
Live attenuated vaccines may be used to prevent nontargeted diseases such as lower respiratory tract infections (LRTIs) due to their nonspecific effects (NSEs).
OBJECTIVE
We aimed to analyze the NSEs of the Japanese encephalitis vaccine on pediatric LRTIs in children aged 25 months to 35 months.
METHODS
A retrospective cohort study was conducted by using a population-based electronic health record database in Zhejiang, China. Enrolled participants were children born from January 1, 2017, to December 31, 2017, and who were inoculated with the live-attenuated Japanese encephalitis vaccine (JE-L) or inactivated Japanese encephalitis vaccine (JE-I) as the most recent vaccine at 24 months of age. The study was carried out between January 1, 2019, and December 31, 2019. All inpatient and outpatient hospital visits for LRTIs among children aged 25 months to 35 months were recorded. The Andersen-Gill model was used to assess the NSEs of JE-L against LRTIs in children and compared with those of JE-I as the most recent vaccine.
RESULTS
A total of 810 children born in 2017 were enrolled, of whom 585 received JE-L (JE-L cohort) and 225 received JE-I (JE-I cohort) as their last vaccine. The JE-L cohort showed a reduced risk of LRTIs (adjusted hazard ratio [aHR] 0.537, 95% CI 0.416-0.693), including pneumonia (aHR 0.501, 95% CI 0.393-0.638) and acute bronchitis (aHR 0.525, 95% CI 0.396-0.698) at 25 months to 35 months of age. The NSEs provided by JE-L were especially pronounced in female children (aHR 0.305, 95% CI 0.198-0.469) and children without chronic diseases (aHR 0.553, 95% CI 0.420-0.729), without siblings (aHR 0.361, 95% CI 0.255-0.511), with more than 30 inpatient and outpatient hospital visits prior to 24 months of age (aHR 0.163, 95% CI 0.091-0.290), or with 5 to 10 inpatient and outpatient hospital visits due to infectious diseases prior to 24 months old (aHR 0.058, 95% CI 0.017-0.202).
CONCLUSIONS
Compared with JE-I, receiving JE-L as the most recent vaccine was associated with lower risk of inpatient and outpatient hospital visits for LRTIs among children aged 25 months to 35 months. The nature of NSEs induced by JE-L should be considered for policymakers and physicians when recommending JE vaccines to those at high risk of infection from the Japanese encephalitis virus.
Topics: Humans; Female; Child; Child, Preschool; Japanese Encephalitis Vaccines; Retrospective Studies; Vaccines; Respiratory Tract Infections; China
PubMed: 38498052
DOI: 10.2196/53040 -
International Journal of Molecular... Feb 2024Severe obesity in young children prompts for a differential diagnosis that includes syndromic conditions. Rapid-Onset Obesity with Hypothalamic Dysfunction,...
High-Titer Anti-ZSCAN1 Antibodies in a Toddler Clinically Diagnosed with Apparent Rapid-Onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation Syndrome.
Severe obesity in young children prompts for a differential diagnosis that includes syndromic conditions. Rapid-Onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD) syndrome is a potentially fatal disorder characterized by rapid-onset obesity associated with hypoventilation, neural crest tumors, and endocrine and behavioral abnormalities. The etiology of ROHHAD syndrome remains to be established, but recent research has been focusing on autoimmunity. We report on a 2-year-old girl with rapid-onset obesity during the first year of life who progressed to hypoventilation and encephalitis in less than four months since the start of accelerated weight gain. The patient had a high titer of anti-ZSCAN1 antibodies (348; reference range < 40), and the increased values did not decline after acute phase treatment. Other encephalitis-related antibodies, such as the anti-NDMA antibody, were not detected. The rapid progression from obesity onset to central hypoventilation with encephalitis warns about the severe consequences of early-onset ROHHAD syndrome. These data indicate that serial measurements of anti-ZSCAN1 antibodies might be useful for the diagnosis and estimation of disease severity. Further research is needed to determine whether it can predict the clinical course of ROHHAD syndrome and whether there is any difference in antibody production between patients with and without tumors.
Topics: Female; Humans; Child, Preschool; Hypoventilation; Autonomic Nervous System Diseases; Hypothalamic Diseases; Pediatric Obesity; Adrenal Gland Neoplasms; Syndrome; Encephalitis
PubMed: 38474067
DOI: 10.3390/ijms25052820 -
Microbiology Spectrum Apr 2024Mosquitoes carry a large number of known and unknown viruses, some of which could cause serious diseases in humans or animals. Metagenomic sequencing for mosquito...
UNLABELLED
Mosquitoes carry a large number of known and unknown viruses, some of which could cause serious diseases in humans or animals. Metagenomic sequencing for mosquito viromes is crucial for understanding the evolutionary history of viruses and preventing emerging mosquito-borne diseases. We collected 1,598 mosquitoes belonging to four species from five counties in Shandong Province, China in 2021. They were grouped by species and sampling locations and subjected to metagenomic next-generation sequencing for the analysis of the viromes. A total of 233,317,352 sequencing reads were classified into 30 viral families and an unclassified group. Comparative analysis showed that mosquitoes in Shandong Province generally possessed host-specific virome. We detected mosquito-borne viruses including Japanese encephalitis virus, Getah virus, and Kadipiro virus in and samples. Phylogenetic analysis showed that these pathogenic viruses may have existed in mosquitoes in Shandong Province for a long time. Meanwhile, we identified 22 novel viruses belonging to seven families and the genus . Our study comprehensively described the viromes of several common mosquito species in Shandong Province, China, and demonstrated the major role of host species in shaping mosquito viromes. Furthermore, the metagenomic data provided valuable epidemiological information on multiple mosquito-borne viruses, highlighting the potential risk of infection transmission.
IMPORTANCE
Mosquitoes are known as the source of various pathogens for humans and animals. , , and have been found to transmit the Getah virus, which has recently caused increasing infections in China. and are the main vectors of Japanese encephalitis virus and have caused epidemics of Japanese encephalitis in China in past decades. These mosquitoes are widely present in Shandong Province, China, leading to a great threat to public health and the breeding industry. This study provided a comprehensive insight into the viromes of several common mosquito species in Shandong Province, China. The metagenomic sequencing data revealed the risks of multiple pathogenic mosquito-borne viruses, including Japanese encephalitis virus, Getah virus, and Kadipiro virus, which are of great importance for preventing emerging viral epidemics.
Topics: Humans; Animals; Phylogeny; Mosquito Vectors; Viruses; Encephalitis Virus, Japanese; Anopheles; Culex
PubMed: 38466099
DOI: 10.1128/spectrum.03932-23 -
Annals of Medicine and Surgery (2012) Mar 2024Japanese encephalitis virus (JEV), an RNA virus transmitted by Culex mosquitoes, primarily cycles between aquatic birds and mosquitoes with pigs as amplifying hosts,... (Review)
Review
Japanese encephalitis virus (JEV), an RNA virus transmitted by Culex mosquitoes, primarily cycles between aquatic birds and mosquitoes with pigs as amplifying hosts, posing a significant global encephalitis threat. The emergence and spread of the JEV in new epidemiological regions, such as recent cases in Australia and nonendemic areas like Pune, India, raise significant concerns. With an estimated 68 000 clinical cases and 13 600 to 20 400 deaths annually, JEV poses a substantial global health threat. The virus primarily affects children, with a case-fatality ratio of 20-30% and long-term neurological sequelae in survivors. The changing epidemiology, influenced by factors like bird migration, climate change, and increased urbanization, contributes to the geographic expansion of JEV. The recent outbreaks underscore the potential for the virus to establish itself in nonendemic regions, posing a threat to populations previously considered at low-risk. With limited treatment options and high rates of neurological complications, continued surveillance, traveler vaccination, and research into treatments are crucial to mitigate the impact of JEV on human health. The evolving scenario necessitates proactive measures to prevent and control the spread of the virus in both endemic and newly affected areas.
PubMed: 38463109
DOI: 10.1097/MS9.0000000000001739 -
Neurology India Jan 2024
Review
Topics: Humans; Encephalitis, Japanese; Encephalitis; Infections; Chronic Disease; Recurrence
PubMed: 38443035
DOI: 10.4103/neurol-india.Neurol-India-D-23-00465 -
Annali Di Igiene : Medicina Preventiva... 2024Japanese encephalitis, caused by the JE virus transmitted by mosquitoes, is the most common type of epidemic encephalitis in Asia. It is endemic in most of South and... (Review)
Review
Japanese encephalitis, caused by the JE virus transmitted by mosquitoes, is the most common type of epidemic encephalitis in Asia. It is endemic in most of South and Southeast Asia, but the number of cases can vary greatly between areas. While many infections do not lead to disease, the symptomatic cases can be very severe and life-threatening. It mainly affects children, whereas adults are generally immune to the disease due to either being infected in childhood or receiving vaccination. However, individuals who are not immune, such as travelers from non-endemic countries, are susceptible to the disease when exposed to the virus for the first time, regardless of age. Without antiviral treatment options, vaccination is the only strategy to establish effective protection against Japanese encephalitis.
Topics: Adult; Child; Animals; Humans; Encephalitis, Japanese; Asia; Vaccination; Culicidae
PubMed: 38436079
DOI: 10.7416/ai.2024.2616