Red-grouper nervous necrosis virus B2 protein negatively regulates fish interferon response by suppressing host transcription directed by RNA polymerase II
2021
Qin, Yinghui | Wang, Yixin | Liu, Jiaoyun | Lu, Yuanan | Liu, Xueqin
Nervous necrosis virus (NNV) infects more than 120 fish species worldwide and causes high mortality and significant economic losses to the aquaculture industry. Among different genotypes of NNV, the red-grouper nervous necrosis virus (RGNNV) genotype is the most widely reported with the highest number of susceptible species. Interferon (IFN) is a powerful cytokine driving host to establish an antiviral response. RGNNV may have an elaborate strategy to overcome the host's IFN-based antiviral response. In this study, we demonstrated that the B2 protein of RGNNV blocked IFN-mediated antiviral response by inhibiting host transcription directed by RNA polymerase II (RNAP II) complex. We firstly found that the upregulation of IFNφ1 promoter activity stimulated by poly(I:C) was suppressed by RGNNV infection. By systematically screening the structural and nonstructural proteins of RGNNV, we identified B2 protein as the virus's most potent antihost protein, which inhibited the IFNφ1 promoter activities stimulated by MDA5, MAVS, TBK1, IRF3, and IRF7 and decrease their protein expression. Importantly, B2 also suppressed the constitutively active cytomegalovirus (CMV) promoter, which indicated that B2 might be a general inhibitor of gene transcription. Moreover, western blotting showed that B2 could decrease RNAP II expression and RNAP II phosphorylation. All these results showed RGNNV blocked host's IFN response by B2 protein directly dysregulating RNAP II expression. To the best of our knowledge, this is the first report about the mechanism of RGNNV for anti-host IFN response. These findings will provide a new insight for further research on the viral infection mechanism and effective strategies to control RGNNV.
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