The Japanese Encephalitis Virus NS1' Protein Inhibits Type I IFN Production by Targeting MAVS.
Dengyuan ZhouQiuyan LiFan JiaLuping ZhangShengfeng WanYunchuan LiYunfeng SongHuanchun ChenShengbo CaoJing YePublished in: Journal of immunology (Baltimore, Md. : 1950) (2020)
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-β 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.
Keyphrases
- dengue virus
- long non coding rna
- cell proliferation
- zika virus
- immune response
- poor prognosis
- dendritic cells
- aedes aegypti
- transcription factor
- long noncoding rna
- binding protein
- dna methylation
- small molecule
- wild type
- sars cov
- type diabetes
- cardiovascular disease
- high throughput
- cardiovascular events
- cell death
- oxidative stress
- protein protein
- pi k akt
- disease virus