title: Interferon alpha (IFNα)-induced TRIM22 interrupts HCV replication by ubiquitinating NS5A.
abstract: TRIM22, a tripartite-motif (TRIM) protein, is upregulated upon interferon alpha (IFNα) 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 IFNα therapy. During the first 24 h following the initiation of IFNα 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 plays an important role in controlling HCV replication in vitro.
authors: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors: Chen
authors: C
authors: Yang
authors: Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors: Xinhao
authors: X
authors: Zhao
authors: Experiment Center of Clinical Medicine, Affiliated Hospital of Binzhou Medical University, Binzhou, China.
authors: Dakang
authors: D
authors: Sun
authors: Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors: Leilei
authors: L
authors: Yang
authors: Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors: Chang
authors: C
authors: Chong
authors: Hepatology Section, First Hospital, University of Jilin, Changchun, China.
authors: Yu
authors: Y
authors: Pan
authors: Hepatology Section, First Hospital, University of Jilin, Changchun, China.
authors: Xiumei
authors: X
authors: Chi
authors: Hepatology Section, First Hospital, University of Jilin, Changchun, China.
authors: Yanhang
authors: Y
authors: Gao
authors: Infectious Diseases Department, Fourth Hospital, University of Jilin, Changchun, China.
authors: Moli
authors: M
authors: Wang
authors: Hepatology Section, First Hospital, University of Jilin, Changchun, China.
authors: Xiaodong
authors: X
authors: Shi
authors: Hepatology Section, First Hospital, University of Jilin, Changchun, China.
authors: Haibo
authors: H
authors: Sun
authors: Hepatology Section, First Hospital, University of Jilin, Changchun, China.
authors: Juan
authors: J
authors: Lv
authors: Hepatology Section, First Hospital, University of Jilin, Changchun, China.
authors: Yuanda
authors: Y
authors: Gao
authors: Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors: Jin
authors: J
authors: Zhong
authors: Hepatology Section, First Hospital, University of Jilin, Changchun, China.
authors: Junqi
authors: J
authors: Niu
authors: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.|Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors: Bing
authors: B
authors: Sun
mesh_terms: D045744:Cell Line, Tumor; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D016174:Hepacivirus / Q000187:drug effects* / Q000254:growth & development / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000821:virology; D022781:Hepatocytes / Q000187:drug effects / Q000276:immunology / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D016898:Interferon-alpha / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D015778:Minor Histocompatibility Antigens; D059748:Proteolysis / Q000187:drug effects; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction; D000070584:Tripartite Motif Proteins; D054875:Ubiquitination / Q000187:drug effects; D019562:Viral Load; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000276:immunology*; D014779:Virus Replication / Q000187:drug effects*; D012324:RNA-Dependent RNA Polymerase
chemical_list: D016898:Interferon-alpha; D015778:Minor Histocompatibility Antigens; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D000070584:Tripartite Motif Proteins; D017361:Viral Nonstructural Proteins; C094314:TRIM22 protein, human; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase