期刊
CELLULAR & MOLECULAR IMMUNOLOGY
卷 13, 期 1, 页码 94-102出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/cmi.2014.131
关键词
HCV; IFN alpha; NS5A; TRIM22; ubiquitin
类别
资金
- 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
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据