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Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 J+Immunol 2016 ; 196 (9): 3877-86 Nephropedia Template TP
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MOV10 provides antiviral activity against RNA viruses by enhancing RIG-I-MAVS-independent IFN induction #MMPMID27016603
J Immunol 2016[May]; 196 (9): 3877-86 PMID27016603show ga
MOV10 (Moloney leukemia virus 10, homolog) is an interferon-inducible RNA helicase, associated with small RNA-induced silencing. Here, we report that MOV10 exhibits antiviral activity, independent of its helicase function, against a number of positive and negative-strand RNA viruses by enhancing type I interferon (IFN) induction. Using a number of CRISPR/Cas9-mediated knockout human cells, we show that IRF3-mediated IFN induction and downstream IFN signaling through IFN receptor was necessary to inhibit virus replication by MOV10. MOV10 enhanced IRF3-mediated transcription of IFN. However, this IFN induction by MOV10 was unique and independent of the known RIG-I/MAVS-mediated RNA-sensing pathway. Upon virus infection, MOV10 specifically required IKK? not TBK1, for its antiviral activity. The important role of MOV10 in mediating antiviral signaling was further supported by the finding that viral proteases from picornavirus family specifically targeted MOV10 as a possible innate immune evasion mechanism. These results establish MOV10, an evolutionary conserved protein involved in RNA silencing, as an antiviral gene against RNA viruses that uses a RLR-independent pathway to enhance IFN response.