PT  - JOURNAL ARTICLE
AU  - Liang, Yisha
AU  - Zhang, Guigen
AU  - Li, Qiheng
AU  - Han, Lin
AU  - Hu, Xiaoyou
AU  - Guo, Yu
AU  - Tao, Wanyin
AU  - Zhao, Xiaomin
AU  - Guo, Mingzhe
AU  - Gan, Tianyu
AU  - Tong, Yimin
AU  - Xu, Yongfen
AU  - Zhou, Zhuo
AU  - Ding, Qiang
AU  - Wei, Wensheng
AU  - Zhong, Jin
TI  - TRIM26 is a critical host factor for HCV replication and contributes to host tropism
AID  - 10.1126/sciadv.abd9732
DP  - 2021 Jan 01
TA  - Science Advances
PG  - eabd9732
VI  - 7
IP  - 2
4099  - http://advances.sciencemag.org/content/7/2/eabd9732.short
4100  - http://advances.sciencemag.org/content/7/2/eabd9732.full
SO  - Sci Adv2021 Jan 01; 7
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.