Journal of Microbiology

The Microbiological Society of Korea (한국미생물학회)
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Hepatitis C Virus Non-structural Protein NS4B Can Modulate an Unfolded Protein Response

  • Zheng Yi (State Key laboratory of virology, College of Life Sciences, Wuhan University) ;
  • Gao Bo (State Key laboratory of virology, College of Life Sciences, Wuhan University) ;
  • Ye Li (State Key laboratory of virology, College of Life Sciences, Wuhan University) ;
  • Kong Lingbao (State Key laboratory of virology, College of Life Sciences, Wuhan University) ;
  • Jing Wei (State Key laboratory of virology, College of Life Sciences, Wuhan University) ;
  • Yang Xiaojun (State Key laboratory of virology, College of Life Sciences, Wuhan University) ;
  • Wu Zhenghui (State Key laboratory of virology, College of Life Sciences, Wuhan University) ;
  • Ye Linbai (State Key laboratory of virology, College of Life Sciences, Wuhan University)
  • Published : 2005.12.01
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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 $\alpha-mannosidase-like$ 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.

Keywords

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