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Viruses Oct 2023Flaviviruses are a family of enveloped viruses with a positive-sense RNA genome, transmitted by arthropod vectors. These viruses are known for their broad cellular... (Review)
Review
Flaviviruses are a family of enveloped viruses with a positive-sense RNA genome, transmitted by arthropod vectors. These viruses are known for their broad cellular tropism leading to infection of multiple body systems, which can include the central nervous system. Neurologic effects of flavivirus infection can arise during both acute and post-acute infectious periods; however, the molecular and cellular mechanisms underlying post-acute sequelae are not fully understood. Here, we review recent studies that have examined molecular and cellular mechanisms that may contribute to neurologic sequelae following infection with the West Nile virus, Japanese encephalitis virus, Zika virus, dengue virus, and St. Louis encephalitis virus. Neuronal death, either from direct infection or due to the resultant inflammatory response, is a common mechanism by which flavivirus infection can lead to neurologic impairment. Other types of cellular damage, such as oxidative stress and DNA damage, appear to be more specific to certain viruses. This article aims to highlight mechanisms of cellular damage that are common across several flavivirus members and mechanisms that are more unique to specific members. Our goal is to inspire further research to improve understanding of this area in the hope of identifying treatment options for flavivirus-associated neurologic changes.
Topics: Animals; Humans; Culicidae; Mosquito Vectors; Flavivirus Infections; Flavivirus; West Nile virus; Zika Virus; Zika Virus Infection
PubMed: 38005878
DOI: 10.3390/v15112200 -
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 -
The spatial-temporal pattern of Japanese encephalitis and its influencing factors in Guangxi, China.Infection, Genetics and Evolution :... Jul 2023Japanese encephalitis (JE) is a major global public health threat. Using Japanese encephalitis incidence data from 2004 to 2010 in Guangxi Province, China, this study...
Japanese encephalitis (JE) is a major global public health threat. Using Japanese encephalitis incidence data from 2004 to 2010 in Guangxi Province, China, this study comprehensively explored the driving forces and the interactive effects between environmental and social factors of Japanese encephalitis using the Geo-detector method. The results indicated that the incidence of Japanese encephalitis showed a fluctuating downward trend from 2004 to 2010. The onset of JE was seasonal, mainly concentrated in June-July, and highly aggregated in northwestern Guangxi. Among the factors associated with Japanese encephalitis, days with temperatures >30 °C, accumulated temperatures >25 °C, slope, the normalized difference vegetation index, the gross domestic product of tertiary industries, the gross domestic product of primary industries and the number of pigs slaughtered showed higher contributions to Japanese encephalitis incidence. An enhanced interactive effect was found between environmental and social factors, and the interaction between days with humidity levels >80% and the gross domestic product of tertiary industries had the greatest combined effect on JE. These findings enhanced the understanding of the combined effect of social and environmental factors on the incidence of Japanese encephalitis and could help improve Japanese encephalitis transmission control and prevention strategies.
Topics: Animals; Swine; Encephalitis, Japanese; China; Incidence; Temperature; Gross Domestic Product
PubMed: 37037290
DOI: 10.1016/j.meegid.2023.105433 -
Emerging Infectious Diseases Dec 2023Japanese encephalitis (JE) is associated with an immense social and economic burden. Published cost-of-illness data come primarily from decades-old studies. To determine...
Japanese encephalitis (JE) is associated with an immense social and economic burden. Published cost-of-illness data come primarily from decades-old studies. To determine the cost of care for patients with acute JE and initial and long-term sequelae from the societal perspective, we recruited patients with laboratory-confirmed JE from the past 10 years of JE surveillance in Bangladesh and categorized them as acute care, initial sequalae, and long-term sequelae patients. Among 157 patients, we categorized 55 as acute, 65 as initial sequelae (53 as both categories), and 90 as long-term sequelae. The average (median) societal cost of an acute JE episode was US $929 ($909), of initial sequelae US $75 ($33), and of long-term sequelae US $47 ($14). Most families perceived the effect of JE on their well-being to be extreme and had sustained debt for JE expenses. Our data about the high cost of JE can be used by decision makers in Bangladesh.
Topics: Humans; Encephalitis, Japanese; Bangladesh; Critical Care; Japanese Encephalitis Vaccines; Encephalitis Virus, Japanese
PubMed: 37987586
DOI: 10.3201/eid2912.230594 -
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 -
The Neurohospitalist Jul 2023
PubMed: 37441216
DOI: 10.1177/19418744231164810 -
H3K27me3 of Rnf19a promotes neuroinflammatory response during Japanese encephalitis virus infection.Journal of Neuroinflammation Jul 2023Histone methylation is an important epigenetic modification that affects various biological processes, including the inflammatory response. In this study, we found that...
Histone methylation is an important epigenetic modification that affects various biological processes, including the inflammatory response. In this study, we found that infection with Japanese encephalitis virus (JEV) leads to an increase in H3K27me3 in BV2 microglial cell line, primary mouse microglia and mouse brain. Inhibition of H3K27me3 modification through EZH2 knockdown and treatment with EZH2 inhibitor significantly reduces the production of pro-inflammatory cytokines during JEV infection, which suggests that H3K27me3 modification plays a crucial role in the neuroinflammatory response caused by JEV infection. The chromatin immunoprecipitation-sequencing (ChIP-sequencing) assay revealed an increase in H3K27me3 modification of E3 ubiquitin ligases Rnf19a following JEV infection, which leads to downregulation of Rnf19a expression. Furthermore, the results showed that Rnf19a negatively regulates the neuroinflammatory response induced by JEV. This is achieved through the degradation of RIG-I by mediating its ubiquitination. In conclusion, our findings reveal a novel mechanism by which JEV triggers extensive neuroinflammation from an epigenetic perspective.
Topics: Animals; Mice; Encephalitis Virus, Japanese; Histones; Encephalitis, Japanese; Inflammation; Encephalitis Viruses, Japanese; Ubiquitin-Protein Ligases
PubMed: 37480121
DOI: 10.1186/s12974-023-02852-4 -
BMC Neuroscience Nov 2023Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus that has no specific treatment except for supportive medical care. JEV is a neurotropic virus that...
BACKGROUND
Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus that has no specific treatment except for supportive medical care. JEV is a neurotropic virus that affects the nervous system and triggers inflammation in the brain.
METHODS
Melatonin is used as a sleep-inducing agent in neurophysiology and may serve as a protective agent against neurological and neurodegenerative diseases. Herein, we investigated the effects of melatonin and the critical roles of the serine/threonine protein phosphatase calcineurin during JEV infection in SK-N-SH neuroblastoma cells.
RESULTS
Melatonin treatment decreased JEV replication and JEV-mediated neurotoxicity. Calcineurin activity was increased by JEV infection and inhibited by melatonin treatment. Through calcineurin regulation, melatonin decreased the JEV-mediated neuroinflammatory response and attenuated JEV-induced autophagy.
CONCLUSIONS
Calcineurin inactivation has a protective effect in JEV-infected neuronal cells, and melatonin is a novel resource for the development of anti-JEV agents.
Topics: Animals; Humans; Encephalitis Virus, Japanese; Calcineurin; Melatonin; Encephalitis, Japanese; Autophagy
PubMed: 37932682
DOI: 10.1186/s12868-023-00832-1 -
Cell Reports Sep 2023Japanese encephalitis (JE) is a vector-borne viral disease that causes acute encephalitis in children. Although vaccines have been developed against the JE virus (JEV),...
Japanese encephalitis (JE) is a vector-borne viral disease that causes acute encephalitis in children. Although vaccines have been developed against the JE virus (JEV), no effective antiviral therapy exists. Our study shows that inhibition of poly(ADP-ribose) polymerase 1 (PARP1), an NAD-dependent (poly-ADP) ribosyl transferase, protects against JEV infection. Interestingly, PARP1 is critical for JEV pathogenesis in Neuro-2a cells and mice. Small molecular inhibitors of PARP1, olaparib, and 3-aminobenzamide (3-AB) significantly reduce clinical signs and viral load in the serum and brains of mice and improve survival. PARP1 inhibition confers protection against JEV infection by inhibiting autophagy. Mechanistically, upon JEV infection, PARP1 PARylates AKT and negatively affects its phosphorylation. In addition, PARP1 transcriptionally upregulates PTEN, the PIP3 phosphatase, negatively regulating AKT. PARP1-mediated AKT inactivation promotes autophagy and JEV pathogenesis by increasing the FoxO activity. Thus, our findings demonstrate PARP1 as a potential mediator of JEV pathogenesis that can be effectively targeted for treating JE.
Topics: Child; Humans; Encephalitis, Japanese; Encephalitis Virus, Japanese; Proto-Oncogene Proteins c-akt; Brain; Poly (ADP-Ribose) Polymerase-1
PubMed: 37676769
DOI: 10.1016/j.celrep.2023.113103 -
Veterinary Sciences May 2024The Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, has a wide host range, extending from pigs and ardeid birds to opportunistic dead-end hosts, such as...
The Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, has a wide host range, extending from pigs and ardeid birds to opportunistic dead-end hosts, such as humans and horses. However, JEV encephalitis infections in aquatic mammals are rare, with only two cases in seals reported to date. Here, we report a lethal case of JEV and co-infection in an aquarium-housed harbor seal in Japan. We isolated JEV from the brain of the dead seal and characterized its phylogeny and pathogenicity in mice. The virus isolate from the seal was classified as genotype GIb, which aligns with recent Japanese human and mosquito isolates as well as other seal viruses detected in China and Korea, and does not exhibit a unique sequence trait distinct from that of human and mosquito strains. We demonstrated that the seal isolate is pathogenic to mice and causes neuronal symptoms. These data suggest that seals should be considered a susceptible dead-end host for circulating JEV in natural settings.
PubMed: 38787188
DOI: 10.3390/vetsci11050215