MCPIP1 ribonuclease exhibits broad-spectrum antiviral effects through viral RNA binding and degradation

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 fir...

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Bibliographic Details
Published in:Nucleic acids research 2013-03, Vol.41 (5), p.3314-3326
Main Authors: Lin, Ren-Jye, Chien, Hsu-Ling, Lin, Shyr-Yi, Chang, Bi-Lan, Yu, Han-Pang, Tang, Wei-Chun, Lin, Yi-Ling
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Conserved Sequence
Dengue Virus - genetics
Dengue Virus - immunology
Dengue Virus - physiology
Encephalitis Virus, Japanese - genetics
Encephalitis Virus, Japanese - immunology
Encephalitis Virus, Japanese - physiology
HEK293 Cells
Host-Pathogen Interactions
Humans
Immunity, Innate
Molecular Sequence Data
Nucleic Acid Enzymes
Protein Binding
Protein Multimerization
Protein Structure, Tertiary
Ribonucleases
RNA Stability
RNA, Viral - metabolism
Transcription Factors - chemistry
Transcription Factors - metabolism
Transcription Factors - physiology
Virus Replication
Zinc Fingers
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Summary: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.
ISSN:0305-1048
1362-4962
DOI:10.1093/nar/gkt019