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Reviews in Medical Virology Sep 2023Monoamine oxidase (MAO) is a membrane-bound mitochondrial enzyme that maintains the steady state of neurotransmitters and other biogenic amines in biological systems... (Review)
Review
Monoamine oxidase (MAO) is a membrane-bound mitochondrial enzyme that maintains the steady state of neurotransmitters and other biogenic amines in biological systems through catalytic oxidation and deamination. MAO dysfunction is closely related to human neurological and psychiatric diseases and cancers. However, little is known about the relationship between MAO and viral infections in humans. This review summarises current research on how viral infections participate in the occurrence and development of human diseases through MAO. The viruses discussed in this review include hepatitis C virus, dengue virus, severe acute respiratory syndrome coronavirus 2, human immunodeficiency virus, Japanese encephalitis virus, Epstein-Barr virus, and human papillomavirus. This review also describes the effects of MAO inhibitors such as phenelzine, clorgyline, selegiline, M-30, and isatin on viral infectious diseases. This information will not only help us to better understand the role of MAO in the pathogenesis of viruses but will also provide new insights into the treatment and diagnosis of these viral diseases.
Topics: Humans; Monoamine Oxidase; Epstein-Barr Virus Infections; COVID-19; Herpesvirus 4, Human; Monoamine Oxidase Inhibitors
PubMed: 37294534
DOI: 10.1002/rmv.2465 -
Antiviral Research Aug 2023Manipulation of the flavivirus genome to accommodate and express a heterologous gene of interest has become an attractive approach for gene delivery and the development...
Manipulation of the flavivirus genome to accommodate and express a heterologous gene of interest has become an attractive approach for gene delivery and the development of viral-vectored vaccines. However, due to the inherent genetic instability of the flavivirus genomes, the construction of recombinant viruses carrying a foreign gene could be problematic and heavily resistant. In this study, the possibility of the Japanese encephalitis virus (JEV) as a stable flavivirus vector for the expression of a foreign gene was assessed using reverse genetics. The full-length cDNA genome of genotype I (GI) JEV inherently possessed excellent stability and manipulability in a bacterial host, while mutations and deletions accumulated in the cDNA genomes of genotype Ⅲ (GⅢ) JEV strains. Using the GI JEV as backbones, we generate a panel of recombinant viruses expressing various foreign genes. All recombinant viruses exhibited excellent genetic stability and efficiently express foreign genes for at least ten serial passages in vitro. In application, a convenient, rapid and reliable image-based assay for neutralizing antibody testing and antiviral drug discovery was established with a mCherry-reporter recombinant virus (rBJ-mCherry). Meanwhile, the recombinant viruses expressing the antigens of the African swine fever virus (ASFV) or Classical swine fever virus (CSFV) could effectively induce antibody responses to the JEV vector and foreign antigens in a mouse vaccination model. Therefore, GI JEV strains could serve as viral vectors accommodating the expression of large foreign genes.
Topics: Mice; Swine; Animals; Encephalitis Virus, Japanese; DNA, Complementary; African Swine Fever Virus; Encephalitis Viruses, Japanese; Viral Vaccines; Gene Expression; Genotype; Encephalitis, Japanese
PubMed: 37301446
DOI: 10.1016/j.antiviral.2023.105652 -
Journal of Virology Dec 2023Central nervous system infection by flaviviruses such as Japanese encephalitis virus, Dengue virus, and West Nile virus results in neuroinflammation and neuronal damage....
Central nervous system infection by flaviviruses such as Japanese encephalitis virus, Dengue virus, and West Nile virus results in neuroinflammation and neuronal damage. However, little is known about the role of long non-coding RNAs (lncRNAs) in flavivirus-induced neuroinflammation and neuronal cell death. Here, we characterized the role of a flavivirus-induced lncRNA named during the infection of neuronal cells. Depletion of during virus infection reduces viral replication and cell death. An increase in GRP78 expression by is responsible for promoting virus replication. Flavivirus infection induces the expression of a cellular protein RBM10, which interacts with . RBM10 and JINR1 promote the proinflammatory transcription factor NF-κB activity, which is detrimental to cell survival.
Topics: Humans; Cell Death; Encephalitis Virus, Japanese; Neuroinflammatory Diseases; NF-kappa B; RNA, Long Noncoding; RNA-Binding Proteins; Neurons; Virus Replication
PubMed: 37991381
DOI: 10.1128/jvi.01183-23 -
Current Medicinal Chemistry Feb 2024Anti-N-methyl-d-aspartate (Anti-NMDA) receptor encephalitis is a rare autoimmune disease, which is caused by antibodies attacking NMDA receptors in the brain. Previous...
BACKGROUND
Anti-N-methyl-d-aspartate (Anti-NMDA) receptor encephalitis is a rare autoimmune disease, which is caused by antibodies attacking NMDA receptors in the brain. Previous studies revealed that this disorder might be induced by vaccination. Vaccination is the most useful strategy to prevent human or animal infectious diseases.
MATERIALS AND METHODS
Although vaccines can produce immunity against diseases, at low risk, they may trigger serious adverse events. Anti-NMDA receptor encephalitis has been studied to be related to the H1N1 (influenza A virus subtype H1N1), tetanus/diphtheria/ pertussis and polio vaccine, Japanese encephalitis, yellow fever, and coronavirus disease 2019 (COVID-19) vaccination. Several cases have been reported that anti-NMDA receptor encephalitis could also be triggered by the human papillomavirus (HPV) vaccine. However, there is a lack of studies to investigate the underlying mechanism.
RESULT
In this paper, the association between anti-NMDA receptor encephalitis and HPV vaccination is discussed in terms of their microRNA (miRNA) biomarkers. Phylogenetic tree and distance similarity analyses are used to explore the relationship between their miRNA biomarkers. The results show a higher degree of similarity between miRNA biomarkers associated with HPV and anti-NMDA receptor encephalitis or related vaccines when compared to the overall miRNAs. It indicates that while the risk of HPV triggering anti-NMDA receptor encephalitis is low, a connection between anti-NMDA receptor encephalitis and HPV vaccination cannot be ruled out.
CONCLUSION
This finding suggests that in cases where individuals receiving HPV vaccination experience psychiatric or neurological symptoms, it should be considered to diagnose anti-NMDA receptor encephalitis, given the exclusion of other possible complications.
PubMed: 38549528
DOI: 10.2174/0109298673264615231124072130 -
The Medical Journal of Australia Jun 2024
Topics: Humans; Australia; Encephalitis, Japanese; Encephalitis Virus, Japanese
PubMed: 38879821
DOI: 10.5694/mja2.52348 -
Cytokine Oct 2023Japanese Encephalitis Virus (JEV) is a neurotropic virus which has the propensity to infect neuronal and glial cells of the brain. Astrocyte-microglia crosstalk leading...
BACKGROUND
Japanese Encephalitis Virus (JEV) is a neurotropic virus which has the propensity to infect neuronal and glial cells of the brain. Astrocyte-microglia crosstalk leading to the secretion of various factors plays a major role in controlling encephalitis in brain. This study focused on understanding the role of astrocytic mediators that further shaped the microglial response towards JEV infection.
METHODS
After establishing JEV infection in C8D1A (mouse astrocyte cell line) and primary astrocyte enriched cultures (PAEC), astrocyte supernatant was used for preparation of conditioned media. Astrocyte supernatant was treated with UV to inactivate JEV and the supernatant was added to N9 culture media in ratio 1:1 for preparation of conditioned media. N9 microglial cells post treatment with astrocyte conditioned media and JEV infection were checked for expression of various inflammatory genes by qRT-PCR, levels of secreted cytokines in N9 cell supernatant were checked by cytometric bead array. N9 cell lysates were checked for expression of proteins - pNF-κβ, IBA-1, NS3 and RIG-I by western blotting. Viral titers were measured in N9 supernatant by plaque assays. Immunocytochemistry experiments were done to quantify the number of infected microglial cells after astrocyte conditioned medium treatment. Expression of different antioxidant enzymes was checked in N9 cells by western blotting, levels of reactive oxygen species (ROS) was detected by fluorimetry using DCFDA dye.
RESULTS
N9 microglial cells post treatment with JEV-infected astrocyte conditioned media and JEV infection were activated, showed an upsurge in expression of inflammatory genes and cytokines both at the transcript and protein levels. These N9 cells showed a decrease in quantity of viral titers and associated viral proteins in comparison to control cells (not treated with conditioned media but infected with JEV). Also, N9 cells upon conditioned media treatment and JEV infection were more prone to undergo oxidative stress as observed by the decreased expression of antioxidant enzymes SOD-1, TRX-1 and increased secretion of reactive oxygen species (ROS).
CONCLUSION
Astrocytic mediators like TNF-α, MCP-1 and IL-6 influence microglial response towards JEV infection by promoting inflammation and oxidative stress in them. As a result of increased microglial inflammation and secretion of ROS, viral replication is lessened in conditioned media treated and JEV infected microglial cells as compared to control cells with no conditioned media treatment but only JEV infection.
Topics: Mice; Animals; Encephalitis Virus, Japanese; Microglia; Reactive Oxygen Species; Astrocytes; Antioxidants; Encephalitis, Japanese; Inflammation; Cytokines; Oxidative Stress
PubMed: 37567102
DOI: 10.1016/j.cyto.2023.156328 -
Journal of Neurochemistry Sep 2023The Flaviviridae family comprises positive-sense single-strand RNA viruses mainly transmitted by arthropods. Many of these pathogens are especially deleterious to the... (Review)
Review
The Flaviviridae family comprises positive-sense single-strand RNA viruses mainly transmitted by arthropods. Many of these pathogens are especially deleterious to the nervous system, and a myriad of neurological symptoms have been associated with infections by Zika virus (ZIKV), West Nile virus (WNV), and Japanese encephalitis virus (JEV) in humans. Studies suggest that viral replication in neural cells and the massive release of pro-inflammatory mediators lead to morphological alterations of synaptic spine structure and changes in the balance of excitatory/inhibitory neurotransmitters and receptors. Glutamate is the predominant excitatory neurotransmitter in the brain, and studies propose that either enhanced release or impaired uptake of this amino acid contributes to brain damage in several conditions. Here, we review existing evidence suggesting that glutamatergic dysfunction-induced by flaviviruses is a central mechanism for neurological damage and clinical outcomes of infection. We also discuss current data suggesting that pharmacological approaches that counteract glutamatergic dysfunction show benefits in animal models of such viral diseases.
Topics: Animals; Humans; Flavivirus; Neurochemistry; Zika Virus Infection; Zika Virus; Glutamic Acid
PubMed: 37603368
DOI: 10.1111/jnc.15935 -
Vector Borne and Zoonotic Diseases... Dec 2023Japanese encephalitis virus (JEV) is a mosquito-borne zoonotic flavivirus and the leading cause of pediatric encephalitis in the Asian Pacific region. The transmission...
Japanese encephalitis virus (JEV) is a mosquito-borne zoonotic flavivirus and the leading cause of pediatric encephalitis in the Asian Pacific region. The transmission cycle primarily involves spp. mosquitoes and Ardeid birds, with domestic pigs () being the source of infectious viruses for the spillover of JEV from the natural endemic transmission cycle into the human population. Although many studies have concluded that domestic pigs play an important role in the transmission cycle of JEV, and infection of humans, the role of feral pigs in the transmission of JEV remains unclear. Since domestic and feral pigs are the same species, and because feral pig populations in the United States are increasing and expanding geographically, the current study aimed to test the hypothesis that if JEV were introduced into the United States, feral pigs might play a role in the transmission cycle. Sinclair miniature pigs, that exhibit the feral phenotype, were intradermally inoculated with JEV genotype Ib. These pigs were derived from crossing miniature domestic pig with four strains of feral pigs and were used since obtaining feral swine was not possible. The Sinclair miniature pigs became viremic and displayed pathological outcomes similar to those observed in domestic swine. Based on these findings, we conclude that in the event of JEV being introduced into the United States, feral pig populations could contribute to establishment and maintenance of a transmission cycle of JEV and could lead to the virus becoming endemic in the United States.
Topics: Animals; Swine; Humans; Child; Encephalitis Virus, Japanese; Encephalitis, Japanese; Swine, Miniature; Birds; Culex; Culicidae; Phenotype
PubMed: 37672628
DOI: 10.1089/vbz.2023.0030 -
Microbial Pathogenesis Sep 2023it was to explore the mechanism of Japanese encephalitis virus (JEV) and micro ribonucleic acid (miRNA) under high-throughput sequencing. 20 experimental mice, with good...
it was to explore the mechanism of Japanese encephalitis virus (JEV) and micro ribonucleic acid (miRNA) under high-throughput sequencing. 20 experimental mice, with good growth status and no disease infection, were selected. The cells used in the experiment included mouse microglial cell line (BV2), mouse neuroblastoma cell line (NA), and mouse brain endothelial cell line (bEnd.3). JEV titration was performed with JEV-infected cells, ribonucleic acid (RNA) in the cells was extracted, and finally the miRNA high-throughput sequencing data was analyzed. Agarose gel electrophoresis showed that the 28S and 18S electrophoresis bands were bright. Among the miRNAs detected in mouse brain tissues, 2986 were down-regulated and 1251 were up-regulated. Among miRNAs detected in NA cells, 4238 the decreasing expression and 2356 were expressed increasingly. In reducing miRNA expression, 1 multiplicity of infection (MOI) of P3 strain infection was more significant than 0.1 MOI. 10 miRNAs with significantly decreasing expression were miR-466d-3p, miR-381-3p, miR-540-3p, miR-466a-3p, miR-467a-3p, miR-574-5p, miR-199a-5p, miR-467a-5p, miR-674-5p, and miR-376b-3p. These were all obviously down-regulated in JEV-infected BV2, NA, and bEnd.3 neurons. High-throughput sequencing of JEV-infected mouse brain tissues and mouse neuronal cells found that JEV infection led to down-regulation of overall miRNA expression in host cells.
Topics: Animals; Mice; Encephalitis Virus, Japanese; MicroRNAs; Encephalitis, Japanese; Cell Line; High-Throughput Nucleotide Sequencing
PubMed: 37482114
DOI: 10.1016/j.micpath.2023.106267 -
Frontiers in Cellular and Infection... 2024Japanese encephalitis (JE) is a notifiable infectious disease in China. Information on every case of JE is reported to the superior health administration department....
BACKGROUND
Japanese encephalitis (JE) is a notifiable infectious disease in China. Information on every case of JE is reported to the superior health administration department. However, reported cases include both laboratory-confirmed and clinically diagnosed cases. This study aimed to differentiate between clinical and laboratory-confirmed cases of Japanese encephalitis virus (JEV) infection, and improve the accuracy of reported JE cases by analyzing the acute-phase serum and cerebrospinal fluid of all reported JE cases in the Sichuan province from 2012 to 2022.
METHODS
All acute-phase serum and/or cerebrospinal fluid samples of the reported JE cases were screened for IgM(ImmunoglobulinM)to JEV using the enzyme-linked immunosorbent assay (ELISA), and the detection of the viral genes of JEV and 9 other pathogens including enterovirus (EV), using reverse transcription PCR was attempted. Epidemiological analyses of JE and non-JE cases based on sex, age, onset time, and geographical distribution were also performed.
RESULTS
From 2012 to 2022, 1558 JE cases were reported in the Sichuan province. The results of serological (JEV-specific IgM) and genetic testing for JEV showed that 81% (1262/1558) of the reported cases were confirmed as JEV infection cases (laboratory-confirmed cases). Among the 296 cases of non-JEV infection, 6 viruses were detected in the cerebrospinal fluid in 62 cases, including EV and the Epstein-Barr virus (EBV), constituting 21% (62/296) of all non-JE cases. Among the 62 non-JEV infection cases with confirmed pathogens, infections with EV and EBV included 17 cases each, herpes simplex virus (HSV-1/2) included 14 cases, varicella- zoster virus included 6 cases, mumps virus included 2 cases, and human herpes viruses-6 included 1 case. Additionally, there were five cases involving mixed infections (two cases of EV/EBV, one case of HSV-1/HSV-2, one case of EBV/HSV-1, and one case of EV/herpes viruses-6). The remaining 234 cases were classified as unknown viral encephalitis cases. Our analysis indicated that those aged 0-15 y were the majority of the patients among the 1558 reported JE cases. However, the incidence of laboratory-confirmed JE cases in the >40 y age group has increased in recent years. The temporal distribution of laboratory-confirmed cases of JE revealed that the majority of cases occurred from May to September each year, with the highest incidence in August.
CONCLUSION
The results of this study indicate that there is a certain discrepancy between clinically diagnosed and laboratory-confirmed cases of JE. Each reported case should be based on laboratory detection results, which is of great importance in improving the accuracy of case diagnosis and reducing misreporting. Our results are not only important for addressing JE endemic to the Sichuan province, but also provide a valuable reference for the laboratory detection of various notifiable infectious diseases in China and other regions outside China.
Topics: Adult; Female; Humans; Male; Antibodies, Viral; Encephalitis Virus, Japanese; Encephalitis, Japanese; Enterovirus; Enterovirus Infections; Epstein-Barr Virus Infections; Herpesvirus 1, Human; Herpesvirus 2, Human; Herpesvirus 4, Human; Immunoglobulin M; Infant, Newborn; Infant; Child, Preschool; Child; Adolescent
PubMed: 38343888
DOI: 10.3389/fcimb.2024.1302314