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. 2021 Dec:263:109265.
doi: 10.1016/j.vetmic.2021.109265. Epub 2021 Oct 21.

African swine fever virus MGF505-11R inhibits type I interferon production by negatively regulating the cGAS-STING-mediated signaling pathway

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African swine fever virus MGF505-11R inhibits type I interferon production by negatively regulating the cGAS-STING-mediated signaling pathway

Kaidian Yang et al. Vet Microbiol. 2021 Dec.

Erratum in

Abstract

African swine fever (ASF) is an acute, hemorrhagic, and highly contact infectious disease caused by African swine fever virus (ASFV) infecting domestic pigs or wild boars, the mortality rate up to 100 %. Evasion of host innate immunity plays a vital role in the pathogenesis of ASFV. Studies have showed that the MGF505 genes involve in regulating the IFN-I response, but its mechanism of action remains poorly understood. In our present study, ASFV MGF505-11R inhibited IFN-β and ISRE activation induced by cGAS, IRF7, IRF3-5D, STING, IKKε and TBK1 accompanied by decreases of IFN-β, ISG15 and ISG56 mRNA transcription. ASFV MGF505-11R interacted with STING, degrading STING expression by the lysosomal, ubiquitin-proteasome and autophagy pathways. Moreover, ASFV MGF505-11R could inhibit the phosphorylation of TBK1 and IRF3 stimulated by cGAS/STING overexpression. Finally, the truncation mutation analysis indicated that the 1-191 aa and 182-360 aa of ASFV MGF505-11R could inhibit cGAS-STING-mediated activation of IFN-β promoters. In short, these results demonstrated that ASFV MGF505-11R involved in regulating the IFN-I response by negatively regulating the cGAS signaling pathway. In summary, this study preliminarily clarified the molecular mechanism of ASFV MGF505-11R gene antagonizing IFN-I-mediated antiviral, which will helpfully provide new strategies for treatment and prevention of ASF.

Keywords: African swine fever virus; IFN-I; MGF505-11R; Signaling pathway.

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