RRC ID 68076
Author Sharma KB, Chhabra S, Aggarwal S, Tripathi A, Banerjee A, Yadav AK, Vrati S, Kalia M.
Title Proteomic landscape of Japanese encephalitis virus-infected fibroblasts.
Journal J Gen Virol
Abstract Advances in proteomics have enabled a comprehensive understanding of host-pathogen interactions. Here we have characterized Japanese encephalitis virus (JEV) infection-driven changes in the mouse embryonic fibroblast (MEF) proteome. Through tandem mass tagging (TMT)-based mass spectrometry, we describe changes in 7.85 % of the identified proteome due to JEV infection. Pathway enrichment analysis showed that proteins involved in innate immune sensing, interferon responses and inflammation were the major upregulated group, along with the immunoproteasome and poly ADP-ribosylation proteins. Functional validation of several upregulated anti-viral innate immune proteins, including an active cGAS-STING axis, was performed. Through siRNA depletion, we describe a crucial role of the DNA sensor cGAS in restricting JEV replication. Further, many interferon-stimulated genes (ISGs) were observed to be induced in infected cells. We also observed activation of TLR2 and inhibition of TLR2 signalling using TLR1/2 inhibitor CU-CPT22-blocked production of inflammatory cytokines IL6 and TNF-α from virus-infected N9 microglial cells. The major proteins that were downregulated by infection were involved in cell adhesion (collagens), transport (solute carrier and ATP-binding cassette transporters), sterol and lipid biosynthesis. Several collagens were found to be transcriptionally downregulated in infected MEFs and mouse brain. Collectively, our data provide a bird's-eye view into how fibroblast protein composition is rewired following JEV infection.
Volume 102(9)
Published 2021-9-1
DOI 10.1099/jgv.0.001657
PMID 34546869
MeSH Animals Cell Adhesion Molecules / metabolism Cell Line Collagen / genetics Cytokines / genetics Cytokines / metabolism Down-Regulation Encephalitis Virus, Japanese / physiology* Encephalitis, Japanese / genetics Encephalitis, Japanese / immunology Encephalitis, Japanese / metabolism* Encephalitis, Japanese / virology* Fibroblasts / immunology Fibroblasts / metabolism* Fibroblasts / virology* Host-Pathogen Interactions Immunity, Innate / genetics Inflammation Interferons / immunology Lipid Metabolism Membrane Proteins / genetics Membrane Proteins / metabolism Membrane Transport Proteins / metabolism Mice Mice, Inbred C57BL Nucleotidyltransferases / genetics Nucleotidyltransferases / metabolism Proteins / metabolism Proteome* Proteomics Signal Transduction Toll-Like Receptor 2 / genetics Toll-Like Receptor 2 / metabolism Up-Regulation
IF 3.376
Human and Animal Cells Atg5^(+/+)MEF(RCB2710)