机构地区:[1]State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China [2]Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China [3]Hepatology Section, First Hospital, University of Jilin, Changchun, China [4]Infectious Diseases Department, Fourth Hospital, University of Jilin, Changchun, China [5]Experiment Center of Clinical Medicine, Affiliated Hospital of Binzhou Medical University, Binzhou, China
出 处:《Cellular & Molecular Immunology》2016年第1期94-102,共9页中国免疫学杂志(英文版)
摘 要: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 TRI M22's targeting of the HCV NSSA protein. NS5A is important for HCV replication and for resistance to I FNa therapy. During the first 24 h following the initiation of I FNa 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 IFNα-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 IFNα treatment and Dlavs an important role in controlling HCV replication in vitro.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 TRI M22's targeting of the HCV NSSA protein. NS5A is important for HCV replication and for resistance to I FNa therapy. During the first 24 h following the initiation of I FNa 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 IFNα-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 IFNα treatment and Dlavs an important role in controlling HCV replication in vitro.
关 键 词:HCV IFNΑ NS5A TRIM22 UBIQUITIN
分 类 号:Q78[生物学—分子生物学] TN946[电子电信—信号与信息处理]
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