Pathogenicity and virulence of Japanese encephalitis virus: Neuroinflammation and neuronal cell damage

Ashraf, Usama; Ding, Zhen; Deng, Suhua; Ye, Jing; Cao, Shengbo; Chen, Zheng

doi:10.1080/21505594.2021.1899674

Cited by 60 publications

(47 citation statements)

References 96 publications

(100 reference statements)

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“…In conclusion, we showed that the motor nerve conduction velocity of sciatic nerve decreased, the latency prolonged and the amplitude decreased in JEV injected rats ,especially on the 6dpi, we know JEV can cause neuroin ammation, including immune cell in ltration and neuronal degeneration, which has been known as a key factor of JEV pathogenesis in human [41] .To date, no speci c treatment has been approved to overcome JE, indicating a need for the development of novel therapies [42] . we showed that ceramide has gone up in host and the MMP9 destroied the tight junction of endothelial cells also increased.The structure of tight junctions in infected nerve segments was less compact with larger cellular distances by transmission electron microscopy.These ndings demonstrate that JEV can cause peripheral nerve damage and the evidence of BNB damage in hopes of identifying potential therapeutic targets for the treatment or prevention of disease.…”

Section: Discussionmentioning

confidence: 82%

Japanese Encephalitis Virus-Induced Peripheral Neuropathy in the Rat Model

Zhang

Yuan

Yang

et al. 2022

Preprint

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Background: Guillain–Barré Syndrome Associated with Japanese encephalitis virus(JEV) infection,the mechanism of JEV which caused peripheral nerve injury remains unknown.Recently, it has been suggested that an altered sphingolipid metabolism may contribute to the pathogenesis of peripheral neuropathy. In light of the emerging evidence of peripheral nerve injury when JEV infected and the evidence in the pathogenesis of neuroimmunity, we aimed to make a rat model which peripheral nerve injury after JEV infection and investigate relevant damage mechanism. Methods: We investigated the infected rat with peripheral neuropathy induced by JEV. The rat exhibited behavioral and pathological signs of peripheral nervous injury. The motor function of rats were determined by clinical scoring and tissue examination.Electrophysiological measurements and transmission electron microscopy was used on sciatic nerves to assess peripheral peripheral nervous injury.ELISA were used to evaluate IFNγ, IL-17,ceramide and acid sphingomyelinase level. Immunofluorescence was performed on sciatic nerves to assess the expression and localization of ceramide and matrix metalloproteinase-9.Results: Japanese encephalitis virus induced peripheral neuropathy in rat,evidenced by the aggravated clinical scores, electrophysiological,transmission electron microscopy,circulating pro-inflammatory cytokines, and histological anomalies, suggesting that demyelination and axonal damage of sciatic nerves. JEV destroyed the tight junction structure of rat’s blood nerve barrier and increased ceramide and matrix metalloproteinase-9.Conclusion:These data suggest that JEV is a potential reason caused peripheral nerve injury in rat model and this model can be used for the investigation of the roles of various cytokines and acid sphingomyelinase,ceramide system in infection-induced peripheral neuropathy. Further investigation of this model could give a better understanding and lead to more effective evidences for JEV infection-associated peripheral neuropathy.

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Section: Discussionmentioning

confidence: 82%

Japanese Encephalitis Virus-Induced Peripheral Neuropathy in the Rat Model

Zhang

Yuan

Yang

et al. 2022

Preprint

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“…Then the infected cells migrate from the periphery to the central nervous system, trigger humor and cell-mediated immune responses and induce the expression of pro-inflammatory cytokines. The activation of microglia will lead to the overproduction of pro-inflammatory mediators and cause extensive destruction of neurons and symptoms of acute encephalitis (Lannes et al, 2017 ; Ashraf et al, 2021 ). The clinical manifestations and prognosis of patients depend on the virulence of the virus and the host immune response.…”

Section: Discussionmentioning

confidence: 99%

Detection of Japanese Encephalitis by Metagenomic Next-Generation Sequencing of Cerebrospinal Fluid: A Case Report and Literature Review

et al. 2022

Front. Cell. Neurosci.

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Japanese encephalitis (JE) is an acute viral central nervous system disease, although less than 1% of patients infected with Japanese encephalitis virus (JEV) result in JE, which has an extremely poor prognosis. The Routine detection methods for JEV are time-consuming or limited by hospital conditions, therefore, need the quicker and sensitive techniques to detect JEV. Here, we reported a 14-year-old female who was admitted to our hospital with a severe fever, progressively headache and unconsciousness. Based on the clinical presentation, Preliminary diagnosis on admission indicated central nervous system infection of suspected viral meningoencephalitis or autoimmune encephalitis. The patient's symptoms were unrelieved after being treated with empiric antiviral therapy. Magnetic resonance imaging (MRI) showed that the lesions were located in the bilateral thalamus, head of caudate nucleus, and right lenticular nucleus, so we had to consider the possibility of Flaviviruses infection. We sent the cerebrospinal fluid (CSF) for metagenomic next-generation sequencing (mNGS) immediately, subsequent result suggested the infection caused by JEV. Two days later the results of the serum agglutination test confirmed that virus immunoglobulin M antibody positive. After a week treatment with intravenous immunoglobulin (IVIG), meanwhile, the lumbar puncture was used to check the pressure and various indicators of the CSF again to evaluate the treatment effect, An decrease in the number of WBC indicates, protein and unique RNA reads that the previous experimental treatment was effective, accompany by temperature and consciousness of the patient was normalized. Two weeks after admission, the patient was transferred to the rehabilitation hospital, MR showed the lesions had disappeared completely after 2 months of follow-up. We believed that mNGS may be an effective method for rapid identification of JE.

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“…Within this context, it is important to note that astrocytes are thought to play a crucial role in flavivirus infections of the CNS by mediating the mechanisms that underlie neurological sequelae such as seizures and epilepsy ( Potokar et al, 2019 ; Zheng et al, 2020 ; Ashraf et al, 2021 ). Indeed, given the anatomic position of astroglia and their homeostatic role in the CNS, one can predict that virus invasion may lead to important functional consequences for the entire CNS upon the interaction of astrocytes with viruses.…”

Section: Mechanisms Of Seizures and Epilepsy Associated With Viral In...mentioning

confidence: 99%

“…This is highly relevant for the spread of infection through the CNS, especially because astrocytes are also more resilient to the lytic effects of flavivirus infection. Interestingly, different flavivirus strains appear to exert different effects on specific astrocyte responses ( Potokar et al, 2019 ; Ashraf et al, 2021 ).…”

Section: Mechanisms Of Seizures and Epilepsy Associated With Viral In...mentioning

confidence: 99%

“…Upon WNV infection, astrocytes also release MMPs and pro-inflammatory cytokines, leading to disruption of the BBB and recruitment of leukocytes ( Ashraf et al, 2021 ). Analysis of autopsied neural tissues from humans with WNV encephalomyelitis revealed WNV infection of both neurons and glia ( van Marle et al, 2007 ).…”

Section: Mechanisms Of Seizures and Epilepsy Associated With Viral In...mentioning

confidence: 99%

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Molecular Mechanisms in the Genesis of Seizures and Epilepsy Associated With Viral Infection

Löscher

Howe

2022

Front. Mol. Neurosci.

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Seizures are a common presenting symptom during viral infections of the central nervous system (CNS) and can occur during the initial phase of infection (“early” or acute symptomatic seizures), after recovery (“late” or spontaneous seizures, indicating the development of acquired epilepsy), or both. The development of acute and delayed seizures may have shared as well as unique pathogenic mechanisms and prognostic implications. Based on an extensive review of the literature, we present an overview of viruses that are associated with early and late seizures in humans. We then describe potential pathophysiologic mechanisms underlying ictogenesis and epileptogenesis, including routes of neuroinvasion, viral control and clearance, systemic inflammation, alterations of the blood-brain barrier, neuroinflammation, and inflammation-induced molecular reorganization of synapses and neural circuits. We provide clinical and animal model findings to highlight commonalities and differences in these processes across various neurotropic or neuropathogenic viruses, including herpesviruses, SARS-CoV-2, flaviviruses, and picornaviruses. In addition, we extensively review the literature regarding Theiler’s murine encephalomyelitis virus (TMEV). This picornavirus, although not pathogenic for humans, is possibly the best-characterized model for understanding the molecular mechanisms that drive seizures, epilepsy, and hippocampal damage during viral infection. An enhanced understanding of these mechanisms derived from the TMEV model may lead to novel therapeutic interventions that interfere with ictogenesis and epileptogenesis, even within non-infectious contexts.

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Pathogenicity and virulence of Japanese encephalitis virus: Neuroinflammation and neuronal cell damage

Cited by 60 publications

References 96 publications

Japanese Encephalitis Virus-Induced Peripheral Neuropathy in the Rat Model

Japanese Encephalitis Virus-Induced Peripheral Neuropathy in the Rat Model

Detection of Japanese Encephalitis by Metagenomic Next-Generation Sequencing of Cerebrospinal Fluid: A Case Report and Literature Review

Molecular Mechanisms in the Genesis of Seizures and Epilepsy Associated With Viral Infection

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