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Nain, M and Muherjee, S and Karmaker, SP and Paton, AW and Paton, JC and Abdin, MZ and Basu, A and Kalia, M and Vrati, S (2017) GRP78 is an important host-factor for Japanese encephalitis virus entry and replication in mammalian cells. Journal of Virology, 91 (10). ISSN 1098-5514

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Official URL: http://jvi.asm.org/

Abstract

Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, is the leading cause of viral 24 encephalitis in South-East Asia with potential to become a global pathogen. Here we identify 25 the Glucose regulated protein 78 (GRP78) as an important host protein for virus entry and 26 replication. Using the plasma membrane fractions from mouse neuronal (Neuro2a) cells, 27 mass spectroscopy analysis identified GRP78 as a protein interacting with recombinant JEV 28 envelope protein domain III. GRP78 was found to express on the plasma membrane of 29 Neuro2a, mouse primary neurons, and human epithelial Huh-7 cells. Antibodies against 30 GRP78 significantly inhibited JEV entry in all three cell types suggesting an important role of 31 the protein in virus entry. Depletion of GRP78 by siRNA significantly blocked JEV entry 32 into Neuro2a cells, further supporting its role in virus uptake. Immunofluorescence studies 33 showed extensive co-localization of GRP78 with JEV envelope protein in virus-infected 34 cells. This interaction was also confirmed by immunoprecipitation studies. Additionally, 35 GRP78 was shown to have an important role in JEV replication, as treatment of cells post 36 virus-entry with Subtilase cytotoxin that specifically cleaved GRP78, led to a substantial 37 reduction in viral RNA replication and protein synthesis resulting in significantly reduced 38 extracellular virus titers. Our results indicate that GRP78, an endoplasmic reticulum chaperon 39 of the HSP70 family, is a novel host factor involved at multiple steps of the JEV life-cycle 40 and could be a potential therapeutic target.

Item Type: Article
Subjects: Neurodegenerative Disorders
Depositing User: Dr. D.D. Lal
Date Deposited: 03 May 2017 09:18
Last Modified: 15 Jan 2018 09:07
URI: http://nbrc.sciencecentral.in/id/eprint/18

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