RT Journal Article
SR Electronic
T1 TRIM26 is a critical host factor for HCV replication and contributes to host tropism
JF Science Advances
JO Sci Adv
FD American Association for the Advancement of Science
SP eabd9732
DO 10.1126/sciadv.abd9732
VO 7
IS 2
A1 Liang, Yisha
A1 Zhang, Guigen
A1 Li, Qiheng
A1 Han, Lin
A1 Hu, Xiaoyou
A1 Guo, Yu
A1 Tao, Wanyin
A1 Zhao, Xiaomin
A1 Guo, Mingzhe
A1 Gan, Tianyu
A1 Tong, Yimin
A1 Xu, Yongfen
A1 Zhou, Zhuo
A1 Ding, Qiang
A1 Wei, Wensheng
A1 Zhong, Jin
YR 2021
UL http://advances.sciencemag.org/content/7/2/eabd9732.abstract
AB Hepatitis C virus (HCV) remains a major human pathogen that requires better understanding of virus-host interactions. In this study, we performed a genome-wide CRISPR-Cas9 screening and identified TRIM26, an E3 ligase, as a critical HCV host factor. Deficiency of TRIM26 specifically impairs HCV genome replication. Mechanistic studies showed that TRIM26 interacts with HCV-encoded NS5B protein and mediates its K27-linked ubiquitination at residue K51, and thus promotes the NS5B-NS5A interaction. Moreover, mouse TRIM26 does not support HCV replication because of its unique six–amino acid insert that prevents its interaction with NS5B. Ectopic expression of human TRIM26 in a mouse hepatoma cell line that has been reconstituted with other essential HCV host factors promotes HCV infection. In conclusion, we identified TRIM26 as a host factor for HCV replication and a new determinant of host tropism. These results shed light on HCV-host interactions and may facilitate the development of an HCV animal model.