TRIM22, a tripartite-motif (TRIM) protein, is upregulated upon interferon alpha (IFNa) 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 IFNa therapy. During the first 24 h following the initiation of IFNa 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 IFNa-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 IFNa treatment and plays an important role in controlling HCV replication in vitro.

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Tripartite motif 34 (TRIM34) is a member of TRIM family that can be highly induced by type I Interferon. Currently little is known about the subcellular localization and biological function of TRIM34. In the present study, confocal microscope assay showed that TRIM34 proteins were mainly distributed in the cytoplasm and part of TRIM34 proteins were localized to the mitochondria in human embryonic kidney 293T (HEK293T) cells. Western blot results demonstrated FLAG-TRIM34 could also be identified in the mitochondrial fractions of HEK293T cells transfected with the 5 0 FLAG-pcDNA3.1-TRIM34 vector. The CCK-8 assay further demonstrated that TRIM34 significantly decreased the viability of HEK293T cells. Nevertheless, TRIM34 had no apparent effect on the cell cycle distribution. Interestingly, flow cytometry showed that TRIM34 could obviously induce apoptosis in HEK293T cells. Moreover, we discovered that TRIM34 promoted apoptosis by inducing the loss of mitochondrial membrane potential (MMP) in HEK293T cells, leading to the release of cytochrome c from mitochondia. In short, these results demonstrate that TRIM34 proteins can localize to the mitochondria and induce apoptosis via the depolarization of MMP in HEK293T cells.