MCPIP1 suppresses hepatitis C virus replication and negatively regulates virus-induced proinflammatory cytokine responses

Ren-Jye Lin, Jan Show Chu, Hsu Ling Chien, Chung Hsin Tseng, Pin Chen Ko, Yung Yu Mei, Wei Chun Tang, Yu Ting Kao, Hui Ying Cheng, Yu Chih Liang, Shyr Yi Lin

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

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 HCVmediated 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 virusinduced inflammation.

Original languageEnglish
Pages (from-to)4159-4168
Number of pages10
JournalJournal of Immunology
Volume193
Issue number8
DOIs
Publication statusPublished - Oct 15 2014

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

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