Interferon alpha (IFN?)-induced TRIM22 interrupts HCV replication by ubiquitinating NS5A.

ABSTRACT: TRIM22, a tripartite-motif (TRIM) protein, is upregulated upon interferon alpha (IFN?) administration to hepatitis C virus (HCV)-infected patients. However, the physiological role of TRIM22 upregulation remains unclear. Here, we describe a potential antiviral function of TRIM22's targeting of the HCV NS5A protein. NS5A is important for HCV replication and for resistance to IFN? therapy. During the first 24 h following the initiation of IFN? treatment, upregulation of TRIM22 in the peripheral blood mononuclear cells (PBMCs) of HCV patients correlated with a decrease in viral titer. This phenomenon was confirmed in the hepatocyte-derived cell line Huh-7, which is highly permissive for HCV infection. TRIM22 over-expression inhibited HCV replication, and Small interfering RNA (siRNA)-mediated knockdown of TRIM22 diminished IFN?-induced anti-HCV function. Furthermore, we determined that TRIM22 ubiquitinates NS5A in a concentration-dependent manner. In summary, our results suggest that TRIM22 upregulation is associated with HCV decline during IFN? treatment and plays an important role in controlling HCV replication in vitro.

SUBMITTER: Yang C 

PROVIDER: S-EPMC4711679 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature