Comparative Proteomics Reveals Important Viral-Host Interactions in HCV-Infected Human Liver Cells

PloS One
Shufeng LiuTony T Wang

Abstract

Hepatitis C virus (HCV) poses a global threat to public health. HCV envelop protein E2 is the major component on the virus envelope, which plays an important role in virus entry and morphogenesis. Here, for the first time, we affinity purified E2 complex formed in HCV-infected human hepatoma cells and conducted comparative mass spectrometric analyses. 85 cellular proteins and three viral proteins were successfully identified in three independent trials, among which alphafetoprotein (AFP), UDP-glucose: glycoprotein glucosyltransferase 1 (UGT1) and HCV NS4B were further validated as novel E2 binding partners. Subsequent functional characterization demonstrated that gene silencing of UGT1 in human hepatoma cell line Huh7.5.1 markedly decreased the production of infectious HCV, indicating a regulatory role of UGT1 in viral lifecycle. Domain mapping experiments showed that HCV E2-NS4B interaction requires the transmembrane domains of the two proteins. Altogether, our proteomics study has uncovered key viral and cellular factors that interact with E2 and provided new insights into our understanding of HCV infection.

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Citations

Feb 23, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Abhishek SinhaElah Pick

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Methods Mentioned

BETA
glycosylation
PCR
immunoprecipitation
pull down
pull downs
affinity purification
immunoprecipitations
pull-down
co-IP
two-hybrid

Software Mentioned

Ingenuity Pathway Analysis
Ingenuity Pathway Analysis ( IPA )

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