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 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.
Department of General Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan. linrenjy@ms67.hinet.net
Ren-Jye
RJ
Lin
Hsu-Ling
HL
Chien
Shyr-Yi
SY
Lin
Bi-Lan
BL
Chang
Han-Pang
HP
Yu
Wei-Chun
WC
Tang
Yi-Ling
YL
Lin
D000595:Amino Acid Sequence; D017124:Conserved Sequence; D003716:Dengue Virus / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D004664:Encephalitis Virus, Japanese / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D057809:HEK293 Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate; D008969:Molecular Sequence Data; D011485:Protein Binding; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D020871:RNA Stability; D012367:RNA, Viral / Q000378:metabolism*; D012260:Ribonucleases; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D014779:Virus Replication; D016335:Zinc Fingers
D012367:RNA, Viral; D014157:Transcription Factors; D012260:Ribonucleases; C510646:ZC3H12A protein, human