Abstract
In this study we have reported the in vivo proteomic changes during Japanese Encephalitis Virus (JEV) infection in combination with in vitro studies which will help in the comprehensive characterization of the modifications in the host metabolism in response to JEV infection. We performed a 2-DE based quantitative proteomic study of JEV-infected mouse brain as well as mouse neuroblastoma (Neuro2a) cells to analyze the host response to this lethal virus. 56 host proteins were found to be differentially expressed post JEV infection (defined as exhibiting ≥1.5-fold change in protein abundance upon JEV infection). Bioinformatics analyses were used to generate JEV-regulated host response networks which reported that the identified proteins were found to be associated with various cellular processes ranging from intracellular protein transport, cellular metabolism and ER stress associated unfolded protein response. JEV was found to invade the host protein folding machinery to sustain its survival and replication inside the host thereby generating a vigorous unfolded protein response, subsequently triggering a number of pathways responsible for the JEV associated pathologies. The results were also validated using a human cell line to correlate them to the human response to JEV. The present investigation is the first report on JEV-host interactome in in vivo model and will be of potential interest for future antiviral research in this field.
Highlights
Viral entry, replication, and assembly are dynamic processes that involve numerous host-pathogen interactions
Japanese Encephalitis Virus (JEV) modulated host proteins were identified by proteomic analyses of JEV-infected mouse brain and JEV-infected Neuro2a cells comparing with their mock-infected controls
We found that the proteins, BiP, HNRNPH1, nucleobindin 1 (NUCB1), HSP70 and aldolase C were up regulated in response to JEV while TCPE, Valosin-containing protein (VCP), 14-3-3, ERP57 and nucleophosmin were down regulated
Summary
Replication, and assembly are dynamic processes that involve numerous host-pathogen interactions. Traditional antiviral drug-discovery approaches were directed against virally encoded enzymes that are essential for viral replication but have failed to be effective. The focus of antiviral research is shifting towards manipulating the host antiviral response by targeting cellular enzymes or cofactors required for the viral life cycle. Viruses are known to enter host cells via various receptormediated/endocytosis-mediated routes and replicate in the cytoplasm of infected cells. During the process, they invade various host systems to promote their own replication and evade the system’s immune response. It is well recognized that identification of host proteins of interest, after additional functional validation, may lead to new discoveries regarding host-virus interactions
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