Immature Core protein of hepatitis C virus induces an unfolded protein response through inhibition of ERAD-L in a yeast model system
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
Version of Record online: 18 JAN 2017 | DOI: 10.1111/gtc.12464
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. Utilizing yeast as a model system, we found that the immature Core inhibits ERAD-L, a degradation system responsible for misfolded/unfolded proteins in the ER lumen, and induces UPR. Requirement of an unfolded protein sensor in the ER lumen suggested that inhibition of ERAD-L is probably responsible for Core-dependent UPR activation.