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.