Antiviral Res. 2020 Jan 8:104705. doi: 10.1016/j.antiviral.2020.104705. [Epub ahead of print]
MCPIP1 inhibits Hepatitis B virus replication by destabilizing viral RNA and negatively regulates the virus-induced innate inflammatory responses.
Li M1, Yang J2, Zhao Y3, Song Y2, Yin S4, Guo J5, Zhang H2, Wang K2, Wei L2, Li S6, Xu W7.
Author information
1
Institute of Biology and Medical Sciences, Soochow University, Building, 703, 199 Ren-ai Road, Suzhou, 215123, China. Electronic address: [email protected].
2
Institute of Biology and Medical Sciences, Soochow University, Building, 703, 199 Ren-ai Road, Suzhou, 215123, China.
3
Central Laboratory, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, 200031, China.
4
Department of Infectious Diseases, Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, 21008, China.
5
Department of Microbiology and Immunology, Stanford University, Stanford, CA, 94305, United States.
6
Central Laboratory, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, 200031, China. Electronic address: [email protected].
7
Institute of Biology and Medical Sciences, Soochow University, Building, 703, 199 Ren-ai Road, Suzhou, 215123, China. Electronic address: [email protected].
Abstract
Monocyte chemotactic protein-induced protein 1 (MCPIP1) is an inflammatory regulator in immune response. Recently, MCPIP1 has also been identified as a host antiviral factor against certain virus infection including human immunodeficiency virus, dengue virus and hepatitis C virus. However, whether MCPIP1 could restrict the replication of hepatitis B virus (HBV), a DNA pararetrovirus belonging to Hepadnaviridae family, has not been investigated. In this study, we found that MCPIP1 expression was up-regulated in mouse livers upon acute HBV replication and in HBV-replicated hepatoma cells or HBV-stimulated macrophages. Enforced MCPIP1 expression by hydrodynamic DNA injection in vivo significantly inhibited HBV replication in the mouse livers. Then in vitro studies by overexpression or knockdown assays in cell-lines identified the direct antiviral effect of MCPIP1 on HBV replication. RNA immunoprecipitation and decay assay further suggested that MCPIP1 potently restricted HBV replication through directly binding viral RNA and degrading RNA via its RNase activity, but not deubiquitinase activity. Moreover, we further verified that MCPIP1 negatively regulated HBV-induced proinflammatory cytokines, such as IL-1β, TNF-α and IL-6 in macrophages. Taken together, our data expand MCPIP1's range of viral targets to DNA virus and also demonstrate the negative regulatory role of MCPIP1 in suppressing virus-induced inflammatory response, suggesting MCPIP1 as a potential therapeutic target for treating HBV-related diseases via inducing a host defense against HBV and reducing inflammatory injury meanwhile.