Immature Core protein of hepatitis C virus induces an unfolded protein response through inhibition of ERAD-L in a yeast model system

详细信息    查看全文

• 作者：Shota Takahashi ; Naoko Sato ; Junichi Kikuchi ; Hideaki Kakinuma ; Jun Okawa ; Yukiko Masuyama ; Singo Iwasa ; Hayato Irokawa ; Gi-Wook Hwang ; Akira Naganuma ; Michinori Kohara and Shusuke Kuge
• 刊名：Genes to Cells
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：22
• 期：2
• 页码：160-173
• 全文大小：900K
• ISSN：1365-2443

文摘

The structural protein Core of hepatitis C virus (HCV), a cytosolic protein, induces endoplasmic reticulum (ER) stress and unfolded protein response (UPR) in hepatocytes, and is responsible for the pathogenesis of persistent HCV infection. Using yeast as a model system, we evaluated mechanisms underlying Core-induced interference of ER homeostasis and UPR, and found that UPR is induced by the immature Core (aa 1–191, Core191) but not by the mature Core (aa 1–177, Core177). Interestingly, Core191 inhibits both ERAD-L, a degradation system responsible for misfolded/unfolded proteins in the ER lumen, and ERAD-M, a degradation system responsible for proteins carrying a misfolded/unfolded region in the ER membrane. In contrast, Core177 inhibits ERAD-M but not ERAD-L. In addition, requirement of an unfolded protein sensor in the ER lumen suggested that inhibition of ERAD-L is probably responsible for Core191-dependent UPR activation. These results implicate inadequate maturation of Core as a trigger for induction of ER stress and UPR.