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 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.

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 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

Protein synthesis in japanese encephalitis virus-infected cells

Virology ◽  
1973 ◽  
Vol 56 (1) ◽  
pp. 95-109 ◽  
Author(s):  
Daniel Shapiro ◽  
Kathleen A. Kos ◽  
Philip K. Russell
Keyword(s):  
Protein Synthesis ◽  
Japanese Encephalitis Virus ◽  
Japanese Encephalitis ◽  
Encephalitis Virus ◽  
Infected Cells

scholarly journals Mesenchymal Stem Cells (MSCs) Coculture Protects [Ca2+]i Orchestrated Oxidant Mediated Damage in Differentiated Neurons In Vitro

Cells ◽  
2018 ◽  
Vol 7 (12) ◽  
pp. 250 ◽  
Author(s):  
Adel Alhazzani ◽  
Prasanna Rajagopalan ◽  
Zaher Albarqi ◽  
Anantharam Devaraj ◽  
Mohamed Hessian Mohamed ◽  
...  
Keyword(s):  
Cell Death ◽  
Transforming Growth Factor ◽  
Neuronal Cells ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Apoptotic Cells ◽  
Sequence Of Events ◽  
Cox 2 ◽  
Anti Inflammatory

Cell-therapy modalities using mesenchymal stem (MSCs) in experimental strokes are being investigated due to the role of MSCs in neuroprotection and regeneration. It is necessary to know the sequence of events that occur during stress and how MSCs complement the rescue of neuronal cell death mediated by [Ca2+]i and reactive oxygen species (ROS). In the current study, SH-SY5Y-differentiated neuronal cells were subjected to in vitro cerebral ischemia-like stress and were experimentally rescued from cell death using an MSCs/neuronal cell coculture model. Neuronal cell death was characterized by the induction of proinflammatory tumor necrosis factor (TNF)-α, interleukin (IL)-1β and -12, up to 35-fold with corresponding downregulation of anti-inflammatory cytokine transforming growth factor (TGF)-β, IL-6 and -10 by approximately 1 to 7 fold. Increased intracellular calcium [Ca2+]i and ROS clearly reaffirmed oxidative stress-mediated apoptosis, while upregulation of nuclear factor NF-B and cyclo-oxygenase (COX)-2 expressions, along with ~41% accumulation of early and late phase apoptotic cells, confirmed ischemic stress-mediated cell death. Stressed neuronal cells were rescued from death when cocultured with MSCs via increased expression of anti-inflammatory cytokines (TGF-β, 17%; IL-6, 4%; and IL-10, 13%), significantly downregulated NF-B and proinflammatory COX-2 expression. Further accumulation of early and late apoptotic cells was diminished to 23%, while corresponding cell death decreased from 40% to 17%. Low superoxide dismutase 1 (SOD1) expression at the mRNA level was rescued by MSCs coculture, while no significant changes were observed with catalase (CAT) and glutathione peroxidase (GPx). Interestingly, increased serotonin release into the culture supernatant was proportionate to the elevated [Ca2+]i and corresponding ROS, which were later rescued by the MSCs coculture to near normalcy. Taken together, all of these results primarily support MSCs-mediated modulation of stressed neuronal cell survival in vitro.

scholarly journals Membrane Permeabilization by Small Hydrophobic Nonstructural Proteins of Japanese Encephalitis Virus

1999 ◽  
Vol 73 (8) ◽  
pp. 6257-6264 ◽  
Author(s):  
Yu-Shiu Chang ◽  
Ching-Len Liao ◽  
Chang-Huei Tsao ◽  
Mei-Chieh Chen ◽  
Chiu-I Liu ◽  
...  
Keyword(s):  
Japanese Encephalitis Virus ◽  
Membrane Permeability ◽  
Japanese Encephalitis ◽  
Cultured Cells ◽  
Encephalitis Virus ◽  
Cell Membrane Permeability ◽  
Hygromycin B ◽  
Cytopathic Effects ◽  
Infected Cells ◽  
Small Hydrophobic

ABSTRACT Infection with Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, may cause acute encephalitis in humans and induce severe cytopathic effects in various types of cultured cells. We observed that JEV replication rendered infected baby hamster kidney (BHK-21) cells sensitive to the translational inhibitor hygromycin B or α-sarcine, to which mock-infected cells were insensitive. However, little is known about whether any JEV nonstructural (NS) proteins contribute to virus-induced changes in membrane permeability. Using an inducibleEscherichia coli system, we investigated which parts of JEV NS1 to NS4 are capable of modifying membrane penetrability. We found that overexpression of NS2B-NS3, the JEV protease, permeabilized bacterial cells to hygromycin B whereas NS1 expression failed to do so. When expressed separately, NS2B alone, but not NS3, was sufficient to alter bacterial membrane permeability. Similarly, expression of NS4A or NS4B also rendered bacteria susceptible to hygromycin B inhibition. Examination of the effect of NS1 to NS4 expression on bacterial growth rate showed that NS2B exhibited the greatest inhibitory capability, followed by a modest repression from NS2A and NS4A, whereas NS1, NS3, and NS4B had only trivial influence with respect to the vector control. Furthermore, when cotransfected with a reporter gene luciferase or β-galactosidase, transient expression of NS2A, NS2B, and NS4B markedly reduced the reporter activity in BHK-21 cells. Together, our results suggest that upon JEV infection, these four small hydrophobic NS proteins have various modification effects on host cell membrane permeability, thereby contributing in part to virus-induced cytopathic effects in infected cells.

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