scholarly journals Pathogenesis and Host Immune Response during Japanese Encephalitis Virus Infection

2021 ◽  
Author(s):  
Swatantra Kumar ◽  
Rajni Nyodu ◽  
Vimal K. Maurya ◽  
Shailendra K. Saxena
Keyword(s):  
Cell Death ◽  
Viral Replication ◽  
Japanese Encephalitis Virus ◽  
Japanese Encephalitis ◽  
Immune Escape ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Encephalitis Virus ◽  
Japanese Encephalitis Virus Infection ◽  
Human Dermis

Japanese Encephalitis Virus (JEV) is a mosquito borne flavivirus infection. Transmission of JEV starts with the infected mosquito bite where human dermis layer act as the primary site of infection. Once JEV makes its entry into blood, it infects monocytes wherein the viral replication peaks up without any cell death and results in production of TNF-α.One of the most characteristics pathogenesis of JEV is the breaching of blood brain barrier (BBB). JEV propagation occurs in neurons that results in neuronal cell death as well as dissemination of virus into astrocytes and microglia leading to overexpression of proinflammatory cytokines. JEV infection results in host cells mediated secretion of various types of cytokines including type-1 IFN along with TNF-α and IFN-γ. Molecule like nitrous oxide (NO) exhibits antiviral activities against JEV infection and helps in inhibiting the viral replication by blocking protein synthesis and viral RNA and also in virus infected cells clearance. In addition, the antibody can also acts an opsonizing agent in order to facilitate the phagocytosis of viral particles, which is mediated by Fc or C3 receptor. This chapter focuses on the crucial mechanism of JEV induced pathogenesis including neuropathogenesis viral clearance mechanisms and immune escape strategies.

Replication-incompetent virions of Japanese encephalitis virus trigger neuronal cell death by oxidative stress in a culture system

2004 ◽  
Vol 85 (2) ◽  
pp. 521-533 ◽  
Author(s):  
Ren-Jye Lin ◽  
Ching-Len Liao ◽  
Yi-Ling Lin
Keyword(s):  
Cell Death ◽  
Japanese Encephalitis Virus ◽  
Japanese Encephalitis ◽  
Neuronal Cells ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Encephalitis Virus ◽  
Host Cell Death ◽  
Infected Cells ◽  
The Media

It has been shown that replication of the Japanese encephalitis virus (JEV) can trigger infected cells to undergo apoptosis. In the present study, it is further demonstrated that replication-incompetent virions of JEV, obtained by short-wavelength ultraviolet (UV) irradiation, could also induce host-cell death. It was found that UV-inactivated JEV (UV-JEV) caused cell death in neuronal cells such as mouse neuroblastoma N18 and human neuronal NT-2 cells, but not in non-neuronal baby hamster kidney BHK-21 fibroblast or human cervical HeLa cells. Only actively growing, but not growth-arrested, cells were susceptible to the cytotoxic effects of UV-JEV. Killing of UV-JEV-infected N18 cells could be antagonized by co-infection with live, infectious JEV, suggesting that virions of UV-JEV might engage an as-yet-unidentified receptor-mediated death-signalling pathway. Characteristically, mitochondrial alterations were evident in UV-JEV-infected N18 cells, as revealed by electron microscopy and a loss of membrane potential. N18 cells infected by UV-JEV induced generation of reactive oxygen species (ROS) as well as the activation of nuclear factor kappa B (NF-κB), and the addition of anti-oxidants or specific NF-κB inhibitors to the media greatly reduced the cytotoxicity of UV-JEV. Together, the results presented here suggest that replication-incompetent UV-JEV damages actively growing neuronal cells through a ROS-mediated pathway.

scholarly journals Antiviral effect of dehydroepiandrosterone on Japanese encephalitis virus infection

2005 ◽  
Vol 86 (9) ◽  
pp. 2513-2523 ◽  
Author(s):  
Chia-Che Chang ◽  
Yen-Chuan Ou ◽  
Shue-Ling Raung ◽  
Chun-Jung Chen
Keyword(s):  
Cell Death ◽  
Japanese Encephalitis Virus ◽  
Japanese Encephalitis ◽  
Apoptotic Cell ◽  
Antiviral Effect ◽  
Encephalitis Virus ◽  
Apoptotic Cell Death ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Japanese Encephalitis Virus Infection

Japanese encephalitis virus (JEV), which causes neurological disorders, completes its life cycle and triggers apoptotic cell death in infected cells. Dehydroepiandrosterone (DHEA), an adrenal-derived steroid, has been implicated in protection against neurotoxicity and protection of animals from viral-induced encephalitis, resulting in an increased survival rate of the animals. Currently, the mechanisms underlying the beneficial effects of DHEA against the virus are largely unknown. In this study, DHEA suppression of JEV replication and virus-induced apoptosis in murine neuroblastoma (N18) cells was investigated. It was found that DHEA suppressed JEV-induced cytopathic effects, JEV-induced apoptotic cell death and JEV propagation in a concentration-dependent manner. Antiviral activity was more efficient in cultures treated with DHEA immediately after viral adsorption compared with that in cultures receiving delayed administration after adsorption or transient exposure before adsorption. JEV-induced cytotoxicity was accompanied by the inactivation of extracellular signal-regulated protein kinase (ERK). Inactivation of ERK by JEV infection was reversed by DHEA. When cells were treated with the ERK inhibitor U0126, DHEA lost its antiviral effect. Activation of ERK by anisomycin mimicked the action of DHEA in suppressing JEV-induced cytotoxicity. DHEA-related compounds, such as its sulfate ester (DHEAS) and pregnenolone, were unable to suppress JEV-induced cytotoxicity and ERK inactivation. The hormone-receptor antagonists ICI 182780 and flutamide failed to abrogate the antiviral effect of DHEA. These findings suggest that the antiviral effect of DHEA is not linked directly to the genomic steroid-receptor pathways and suggest that the signalling pathways of ERK play a role in the antiviral action of DHEA.

scholarly journals Elevation of Cleaved p18 Bax Levels Associated with the Kinetics of Neuronal Cell Death during Japanese Encephalitis Virus Infection

2019 ◽  
Vol 20 (20) ◽  
pp. 5016
Author(s):  
Prapimpun Wongchitrat ◽  
Arisara Samutpong ◽  
Hatairat Lerdsamran ◽  
Jarunee Prasertsopon ◽  
Montri Yasawong ◽  
...  
Keyword(s):  
Cell Death ◽  
Japanese Encephalitis Virus ◽  
Japanese Encephalitis ◽  
Cell Apoptosis ◽  
Neuronal Apoptosis ◽  
Apoptotic Cell ◽  
Neuronal Cell ◽  
Encephalitis Virus ◽  
Apoptotic Cell Death ◽  
Human Neuroblastoma

Japanese encephalitis virus (JEV) infection induces uncontrolled neuronal apoptosis, leading to irreversible brain damage. However, the mechanism of JEV-induced neuronal apoptosis has not been clearly elucidated. This study aimed to investigate both virus replication and neuronal cell apoptosis during JEV infection in human neuroblastoma SH-SY5Y cells. As a result, the kinetic productions of new viral progeny were time- and dose-dependent. The stimulation of SH-SY5Y cell apoptosis was dependent on the multiplicity of infections (MOIs) and infection periods, particularly during the late period of infection. Interestingly, we observed that of full-length Bax (p21 Bax) level started to decrease, which corresponded to the increased level of its cleaved form (p18 Bax). The formation of p18 Bax resulting in cytochrome c release into the cytosol appeared to correlate with JEV-induced apoptotic cell death together with the activation of caspase-3/7 activity, especially during the late stage of a robust viral infection. Therefore, our results suggest another possible mechanism of JEV-induced apoptotic cell death via the induction of the proteolysis of endogenous p21 Bax to generate p18 Bax. This finding could be a new avenue to facilitate novel drug discovery for the further development of therapeutic treatments that could relieve neuronal damage from JEV infection.

scholarly journals Screening of FDA-Approved Drugs for Inhibitors of Japanese Encephalitis Virus Infection

2017 ◽  
Vol 91 (21) ◽  
Author(s):  
Shaobo Wang ◽  
Yang Liu ◽  
Jiao Guo ◽  
Peilin Wang ◽  
Leike Zhang ◽  
...  
Keyword(s):  
Virus Infection ◽  
Viral Replication ◽  
Japanese Encephalitis Virus ◽  
Japanese Encephalitis ◽  
Transmembrane Domain ◽  
Specific Treatment ◽  
Encephalitis Virus ◽  
Japanese Encephalitis Virus Infection ◽  
Approved Drugs ◽  
Fda Approved Drugs

ABSTRACT Japanese encephalitis virus (JEV), an arthropod-borne flavivirus, is a major cause of acute viral encephalitis in humans. No approved drug is available for the specific treatment of JEV infections, and the available vaccines are not effective against all clinical JEV isolates. In the study described here, a high-throughput screening of an FDA-approved drug library for inhibitors of JEV was performed. Five hit drugs that inhibited JEV infection with a selective index of >10 were identified. The antiviral activities of these five hit drugs against other flavivirus, including Zika virus, were also validated. As three of the five hit drugs were calcium inhibitors, additional types of calcium inhibitors that confirmed that calcium is essential for JEV infection, most likely during viral replication, were utilized. Adaptive mutant analysis uncovered that replacement of Q130, located in transmembrane domain 3 of the nonstructural NS4B protein, which is relatively conserved in flaviviruses, with R or K conferred JEV resistance to manidipine, a voltage-gated Ca2+ channel (VGCC) inhibitor, without an apparent loss of the viral growth profile. Furthermore, manidipine was indicated to protect mice against JEV-induced lethality by decreasing the viral load in the brain, while it abrogated the histopathological changes associated with JEV infection. This study provides five antiflavivirus candidates and identifies cytoplasmic calcium to be a novel antiviral target for the treatment of JEV infection. The findings reported here provide therapeutic possibilities for combating infections caused by flaviviruses. IMPORTANCE No approved therapy for the treatment of Japanese encephalitis virus infection is currently available. Repurposing of approved drugs would accelerate the development of a therapeutic stratagem. In this study, we screened a library of FDA-approved drugs and identified five hit drugs, especially calcium inhibitors, exerting antiflavivirus activity that blocked viral replication. The in vivo efficacy and toxicity of manidipine were investigated with a mouse model of JEV infection, and the viral target was identified by generating an adaptive mutant.

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

Virulence ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 968-980
Author(s):  
Usama Ashraf ◽  
Zhen Ding ◽  
Shunzhou Deng ◽  
Jing Ye ◽  
Shengbo Cao ◽  
...  
Keyword(s):  
Japanese Encephalitis Virus ◽  
Japanese Encephalitis ◽  
Cell Damage ◽  
Neuronal Cell ◽  
Encephalitis Virus

Astrocytic alteration induced by Japanese encephalitis virus infection

Neuroreport ◽  
2000 ◽  
Vol 11 (9) ◽  
pp. 1933-1937 ◽  
Author(s):  
Chun-Jung Chen ◽  
Su-Lan Liao ◽  
Ming-Der Kuo ◽  
Yu-Ming Wang
Keyword(s):  
Virus Infection ◽  
Japanese Encephalitis Virus ◽  
Japanese Encephalitis ◽  
Encephalitis Virus ◽  
Japanese Encephalitis Virus Infection
Sign in / Sign up

Export Citation Format

Share Document