Title Hepatitis C Virus Non-structural Protein NS4B Can Modulate an Unfolded Protein Response
Author Yi Zheng, Bo Gao, Li Ye, Lingbao Kong, Wei Jing, Xiaojun Yang, Zhenghui Wu, and Linbai Ye*
Address State Key laboratory of virology, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, P.R.China
Bibliography Journal of Microbiology, 43(6),529-536, 2005,
DOI
Key Words hepatitis C virus (HCV), non-structural protein NS4B, unfolded protein response (UPR)
Abstract Viral infection causes stress to the endoplasmic reticulum (ER). The response to endoplasmic reticulum stress, known as the unfolded protein response (UPR), is designed to eliminate misfolded proteins and allow the cell to recover. The role of hepatitis C virus (HCV) non-structural protein NS4B, a component of the HCV replicons that induce UPR, is incompletely understood. We demonstrate that HCV NS4B could induce activating transcription factor (ATF6) and inositol-requiring enzyme 1 (IRE1), to favor the HCV subreplicon and HCV viral replication. HCV NS4B activated the IRE1 pathway, as indicated by splicing of X box-binding protein (Xbp-1) mRNA. However, transcriptional activation of the XBP-1 target gene, EDEM (ER degradation-enhancing a-mannosidase-like protein, a protein degradation factor), was inhibited. These results imply that NS4B might induce UPR through ATF6 and IRE1-XBP1 pathways, but might also modify the outcome to benefit HCV or HCV subreplicon replication.
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