African swine fever virus A179L inhibits interferon induced transmembrane protein 1 activation of NF-κB pathway.

African swine fever virus (ASFV) encodes over 150 viral proteins, several of which have roles in evading innate immune responses. Among these, A179L is the only Bcl-2-like protein involved in ASFV-induced apoptosis, but its other functions remain poorly understood. This study found that A179L inhibits the NF-κB signaling pathway, reducing the production of pro-inflammatory cytokines. Mechanistically, A179L was found to interact with Interferon Induced Transmembrane Protein 1(IFITM1), leading to enhanced recruitment of MARCH8 to IFITM1 and degradation of IFITM1 by K48 ubiquitination, thereby suppressing NF-κB activation. Interestingly, it was observed for the first time that IFITM1 can activate the NF-κB signaling pathway by interacting with IKKβ and promoting its phosphorylation. Additionally, inhibiting A179L gene expression in ASFV-infected cells via RNA silencing increased the transcription levels of tumor necrosis factor-α and interleukin-1β. Subsequently, a recombinant ASFV strain, ASFV-ΔA179L, was generated by knocking out the A179L gene from the virus genome. The results demonstrated that ASFV-ΔA179L enhanced the expression of pNF-κB and pro-inflammatory cytokines. The findings of this study suggest a novel mechanism through which A179L inhibits the NF-κB signaling pathway by degrading IFITM1.