The African Swine Fever Virus pH108R Protein Negatively Regulates Innate Immune Response by Inhibiting NF-kappaB Activation.

The NF-?B pathway is an essential signaling cascade in the defence against viral infections, including African swine fever virus (ASFV) infection. ASFV encodes more than 151 proteins via its own transcription machinery and possesses a great capacity to evade or subvert antiviral innate immune responses. Although some of these viral proteins have been reported, many remain unknown. In this study,we find pH108R, an inner envelope protein of ASFV, can significantly downregulated NF-?B activation induced by IL-1ß or TNFa. The overexpression of pH108R suppresses transcription of several proinflammatory cytokines such as IL-6, IL-8,and TNFa induced by IL-1ß or TNFa in HEK293T cells. Consistently, the levels of phosphorylated p65 and I?Ba were decreased in pH108R overexpression cells after IL-1ß and TNFa stimulation. In addition,Transcriptome sequencing showed that it could significantly down-regulate the expression of TNF-induced immune and inflammatory genes in PK-15 cells. Collectively, our study indicates that ASFV pH108R markedly suppresses NF-?B activation stimulated by IL-1ß and TNFa, clarifies the immunosuppressive activity of pH108R and provides a new perspective for analyzing the immune escape of African swine fever. Overall design: RNA-seq profiling of pH108R overexpression cells and control cells, treated with TNFa or not.