MCPIP1 Suppresses Hepatitis C Virus Replication and Negatively Regulates Virus-Induced Proinflammatory Cytokine Responses
| Autor: | Yu Chih Liang, Yu Ting Kao, Wei Chun Tang, Chung Hsin Tseng, Shyr Yi Lin, Pin Chen Ko, Hui Ying Cheng, Jan Show Chu, Yung Yu Mei, Ren-Jye Lin, Hsu Ling Chien |
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| Rok vydání: | 2014 |
| Předmět: |
Hepatitis C virus
Immunology Hepacivirus Biology Virus Replication medicine.disease_cause Virus Proinflammatory cytokine Ribonucleases RNA interference Cell Line Tumor medicine Humans Immunology and Allergy RNA Small Interfering Chemokine CCL2 Gene knockdown Interleukin-6 Tumor Necrosis Factor-alpha RNA-Binding Proteins virus diseases RNA Hepatitis C Chronic Virology digestive system diseases Protein Structure Tertiary NS2-3 protease HEK293 Cells Liver Viral replication Mutation RNA Viral RNA Interference Ubiquitin-Specific Proteases Transcription Factors |
| Zdroj: | The Journal of Immunology. 193:4159-4168 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Human MCP-1–induced protein 1 (MCPIP1, also known as ZC3H12A and Regnase-1) plays important roles in negatively regulating the cellular inflammatory response. Recently, we found that as an RNase, MCPIP1 has broad-spectrum antiviral effects by targeting viral RNA. In this study, we demonstrated that MCPIP1 expression was induced by hepatitis C virus (HCV) infection in Huh7.5 hepatoma cells. MCPIP1 expression was higher in liver tissue from patients with chronic HCV infection compared with those without chronic HCV infection. Knockdown of MCPIP1 increased HCV replication and HCV-mediated expression of proinflammatory cytokines, such as TNF-α, IL-6, and MCP-1. However, overexpression of MCPIP1 significantly inhibited HCV replication and HCV-mediated expression of proinflammatory cytokines. Various mutants of functional domains of MCPIP1 showed disruption of the RNA binding and oligomerization abilities, as well as RNase activity, but not deubiquitinase activity, which impaired the inhibitory activity against HCV replication. On immunocytochemistry, MCPIP1 colocalized with HCV RNA. Use of a replication-defective HCV John Cunningham 1/AAG mutant and in vitro RNA cleavage assay demonstrated that MCPIP1 could directly degrade HCV RNA. MCPIP1 may suppress HCV replication and HCV-mediated proinflammatory responses with infection, which might contribute to the regulation of host defense against the infection and virus-induced inflammation. |
| Databáze: | OpenAIRE |
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