Research
| Title： | Grass carp cGASL negatively regulates fish IFN response by targeting MITA |
|---|---|
| First author： | Zhou, Yu; Lu, Long-Feng; Lu, Xiao-Bing; Li, Shun; Zhang, Yong-An |
| Journal： | FISH & SHELLFISH IMMUNOLOGY |
| Years： | 2019 |
| DOI： | 10.1016/j.fsi.2019.10.010 |
| Abstract： | Mammalian cyclic GMP-AMP synthase (cGAS) senses double-stranded (ds) DNA in the cytosol to activate the innate antiviral response. In the present study, a cGAS-like gene, namely cGASL, was cloned from grass carp Ctenopharyngodon idellus, and its role as a negative regulator of the IFN response was revealed. Phylogenetic analysis indicated that cGASL was evolutionarily closest to cGAS, but was not a true ortholog of cGAS. Overexpression of cGASL inhibited poly LC-stimulated grass carp (gc)IFN1pro and ISRE activities. In addition, MITA-, but not TBK1-mediated activation of gclFNlpro was impaired by cGASL. Co-immunoprecipitation and Western blot experiments indicated that cGASL interacted with MITA and TBK1, resulting in a reduction in the phosphorylation of MITA. Lastly, overexpression of cGASL reduced the transcriptional levels of several IFNstimulated genes activated by MITA. Collectively, these data suggest that cGASL is a negative regulator of IFN response by targeting MITA in fish. |
