MOV10 provides antiviral activity against RNA viruses by enhancing IFN induction through IKKε and IRF3. (INC8P.441)
| Autor: | Rolando Cuevas, Veit Hornung, Carolyn Coyne, Saumendra Sarkar |
|---|---|
| Rok vydání: | 2014 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 192:187.14-187.14 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.192.supp.187.14 |
| Popis: | MOV10 (Moloney leukemia virus 10, homolog) is an interferon-inducible putative DEAG-containing RNA helicase, which has been known to be associated with the RNA-induced silencing complex (RISC). Although, it is known to inhibit HIV-1 replication, analysis of its border antiviral activity and the mechanism has not been explored. Here, we report that MOV10 exhibits antiviral activity against a number of RNA viruses including EMCV, CVB, SeV and VSV by enhancing IFN induction. The antiviral activity of MOV10 is dependent on IFN signaling, and stable expression of MOV10 enhances IRF3 dimerization and IFN/ISG induction. Using various knockout cells combined with siRNA knockdowns, we show that MOV10-mediated IRF3 activation and IFN/ISG induction is not dependent on RIG-I/MAVS-mediated RNA sensing. Upon virus infection MOV10 specifically interacts and activates IKKε to induce IRF3 activation without involving TBK1. The important role of MOV10 in mediating antiviral signaling is further supported by our findings that CVB 3Cpro protease specifically targets MOV10 for degradation as a possible innate immune evasion mechanism. Taken together, these results establish MOV10, an evolutionary conserved protein, as an antiviral gene that uses a novel signaling pathway to enhance IFN response. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|