| First Author | Zhou D | Year | 2020 |
| Journal | J Immunol | Volume | 204 |
| Issue | 5 | Pages | 1287-1298 |
| PubMed ID | 31996459 | Mgi Jnum | J:285619 |
| Mgi Id | MGI:6392188 | Doi | 10.4049/jimmunol.1900946 |
| Citation | Zhou D, et al. (2020) The Japanese Encephalitis Virus NS1' Protein Inhibits Type I IFN Production by Targeting MAVS. J Immunol 204(5):1287-1298 |
| abstractText | Japanese encephalitis virus (JEV) is a mosquito-borne Flavivirus that causes severe neurologic disease in humans. NS1' is a NS1-related protein only reported in the Japanese encephalitis serogroup members of Flavivirus It is produced through programmed -1 ribosomal frameshift in NS2A. Our previous study demonstrated that JEV NS1' could antagonize type I IFN (IFN-I) production, but the mechanism is still unclear. In the current study, we found that JEV NS1' inhibits the expression of MAVS, and knockdown of MAVS hampers inhibition of IFN-beta induction by NS1', suggesting that JEV NS1' inhibits IFN-I production by targeting MAVS. This finding is further supported by the result of the in vivo assay that showed the similar mortality caused by NS1'-deficient virus and its wild type virus in MAVS-deficient mice. Based on our previous sequencing results of noncoding RNA in JEV-infected cells, microRNA-22 (miR-22) was identified to be a key regulator for MAVS expression during JEV infection. Furthermore, we demonstrated that JEV NS1' could induce the expression of miR-22 by increasing the binding of transcriptional factors, CREB and c-Rel, to the promoter elements of miR-22. Taken together, our results reveal a novel mechanism by which JEV NS1' antagonizes host MAVS by regulating miR-22, thereby inhibiting the IFN-I production and facilitating viral replication. |
