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

2017 ◽  
Vol 22 (2) ◽  
pp. 160-173 ◽  
Author(s):  
Shota Takahashi ◽  
Naoko Sato ◽  
Junichi Kikuchi ◽  
Hideaki Kakinuma ◽  
Jun Okawa ◽  
...  
Hepatology ◽  
2008 ◽  
Vol 48 (4) ◽  
pp. 1054-1061 ◽  
Author(s):  
Donna Sir ◽  
Wen-ling Chen ◽  
Jinah Choi ◽  
Takaji Wakita ◽  
T.S. Benedict Yen ◽  
...  

2013 ◽  
Vol 432 (2) ◽  
pp. 326-332 ◽  
Author(s):  
Yoshiyasu Shinohara ◽  
Kento Imajo ◽  
Masato Yoneda ◽  
Wataru Tomeno ◽  
Yuji Ogawa ◽  
...  

Biochimie ◽  
2020 ◽  
Vol 168 ◽  
pp. 17-27
Author(s):  
Céline Hernandez ◽  
Etienne B. Blanc ◽  
Véronique Pène ◽  
Béatrice Le-Grand ◽  
Maxime Villaret ◽  
...  

2013 ◽  
Vol 7 (1) ◽  
pp. 37-40 ◽  
Author(s):  
Philip A Egan ◽  
Michal Sobkowiak ◽  
Shiu-Wan Chan

Unfolded protein response (UPR) is a cellular adaptive response which functions to reduce stress caused by misfolded proteins in the endoplasmic reticulum (ER). We and others have previously shown that infection with hepatitis C virus (HCV) or expression of the viral proteins can trigger the UPR. HCV is a single-stranded positive-sense RNA virus causing chronic diseases in humans. Its genome encodes two envelope proteins E1 and E2 that mature in the ER to form non-covalently bound native complex and disulphide-bonded aggregates. Apart from the ER targeting proteins, cytosolic forms have been documented. We have previously shown that the ER-targeting E1 and E2 are capable of eliciting the UPR whereas others have shown that the cytosolic-targeting E2 can bind to the ER stress kinase PERK to dampen the UPR. In this report, we further show that the other envelope protein E1, in its cytosolic form, can also bind PERK and dampen the UPR. Using GST-pulldown assay, we show that E1 binds to the cytoplasmic domain of PERK, suggesting interaction of E1 and PERK takes place in the cytoplasm. Using reporter gene assay and Western blotting, we show that cytosolic E1 can repress UPR-induced BiP and CHOP promoter activity and reduce UPR-induced CHOP expression level. Altogether these results suggest opposing functions of ER- and cytosolic forms of HCV envelope proteins depending on their subcellular localization.


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