Journal
CELLULAR & MOLECULAR IMMUNOLOGY
Volume 13, Issue 1, Pages 94-102Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/cmi.2014.131
Keywords
HCV; IFN alpha; NS5A; TRIM22; ubiquitin
Categories
Funding
- National 973 Key Project [2013CB530504]
- National 863 Key Project [2012AA020103]
- National Science and Technology Major Projects [2013ZX10004-101-005, 2012ZX10002-007-003, 2013ZX10004-003-003]
- National Natural Science Foundation of China [31030029, 31230024, 81361120409]
- CAS/SAFEA International Partnership Program for Creative Research Teams
- NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM [R01AA020103] Funding Source: NIH RePORTER
Ask authors/readers for more resources
TRIM22, a tripartite-motif (TRIM) protein, is upregulated upon interferon alpha (IFN alpha) 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 IFN alpha-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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available