TRIM26 is a critical host factor for HCV replication and contributes to host tropism

Academic Article

Abstract

  • 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.
  • Authors

    Published In

  • Science Advances  Journal
  • Digital Object Identifier (doi)

    Author List

  • Liang Y; Zhang G; Li Q; Han L; Hu X; Guo Y; Tao W; Zhao X; Guo M; Gan T
  • Volume

  • 7
  • Issue

  • 2