Pathogenesis and Host Immune Response during Japanese Encephalitis Virus Infection

Abstract

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.

Antiviral and anti‐inflammatory activity of natural compounds against Japanese encephalitis virus via inhibition of NS5 protein and regulation of key immune and inflammatory signaling pathways

“…These proteins are crucial for the entry, maturation, replication, and release of virus in the host cells. 6 Envelope, nonstructural protein-1, JEV protease, helicase/nucleoside triphosphatase, and RNA-dependent RNA polymerase (NS5) of JEV have been targeted to design direct antiviral agents against JEV. 7 Therefore, in pursuit of anti-JEV agents, we searched the Indian Medicinal Plants, Phytochemistry, and Therapeutics (IMPPAT) and PubMed databases for medicinal plants having "antiviral" and "antiinflammatory" activities.…”

“…This genome encodes for a single polyprotein of approximately 3400 amino acids that is processed into three structural proteins (capsid, precursor membrane, and envelope) and seven nonstructural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5). These proteins are crucial for the entry, maturation, replication, and release of virus in the host cells 6 . Envelope, nonstructural protein‐1, JEV protease, helicase/nucleoside triphosphatase, and RNA‐dependent RNA polymerase (NS5) of JEV have been targeted to design direct antiviral agents against JEV 7 …”

Unveiling the Hidden Regulators: The Impact of lncRNAs on Zoonoses

“…This process also increases vascular permeability, causing hemorrhage and multiorgan involvement [ 109 ]. JEV, on the other hand, followed by mosquito bites, enters the mononuclear-phagocyte system and undergoes replication [ 110 ]. It subsequently leads to a robust viremia in individuals due to weakened immune systems, allows the penetration of the blood–brain barrier, and causes extensive meningoencephalitis [ 111 , 112 ].…”

Recent advances to overcome the burden of Japanese encephalitis: A zoonotic infection with problematic early detection

“…Generally, the increased pro-inflammatory cytokine by the infected dendritic cells results in the breakdown of the BBB (blood brain barrier) and hence, leads to the CNS infection. 37 In the other way, the host recognises the PAMPs (pathogen-associated molecular patterns) with the help of PRR (pattern recognition receptor) and activates the innate immunity, 38 which will further initiate the signalling cascade leading to an increase in the interferon, inflammatory cytokines, and chemokines. 39,40 These increased IFNs can instigate the JAK-STAT signalling that transcribes the interferon-related genes which target the virus and stop its anti-viral activity inside humans.…”