MCPIP1 ribonuclease exhibits broad-spectrum antiviral effects through viral RNA binding and degradation |
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| Authors: | Ren-Jye Lin Hsu-Ling Chien Shyr-Yi Lin Bi-Lan Chang Han-Pang Yu Wei-Chun Tang Yi-Ling Lin |
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| Affiliation: | 1Department of General Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan, 2Department of Primary Care Medicine, Taipei Medical University Hospital, Taipei 110, Taiwan, 3Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan, 4Genomics Research Center, Academia Sinica, Taipei 115, Taiwan and 5Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan |
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| Abstract: | Monocyte chemoattractant protein 1-induced protein 1 (MCPIP1), belonging to the MCPIP family with highly conserved CCCH-type zinc finger and Nedd4-BP1, YacP Nuclease domains, has been implicated in negative regulation of the cellular inflammatory responses. In this report, we demonstrate for the first time that this RNA-binding nuclease also targets viral RNA and possesses potent antiviral activities. Overexpression of the human MCPIP1, but not MCPIP2, MCPIP3 or MCPIP4, inhibited Japanese encephalitis virus (JEV) and dengue virus (DEN) replication. The functional analysis of MCPIP1 revealed that the activities of RNase, RNA binding and oligomerization, but not deubiqutinase, are required for its antiviral potential. Furthermore, infection of other positive-sense RNA viruses, such as sindbis virus and encephalomyocarditis virus, and negative-sense RNA virus, such as influenza virus, as well as DNA virus, such as adenovirus, can also be blocked by MCPIP1. Moreover, the endogenous MCPIP1 gene expression was induced by JEV and DEN infection, and knockdown of MCPIP1 expression enhanced the replication of JEV and DEN in human cells. Thus, MCPIP1 can act as a host innate defense via RNase activity for targeting and degrading viral RNA. |
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