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

The NF-κB pathway is an important signal for the body to respond to viral invasion and produce inflammatory responses. African swine fever virus (ASFV) can not only activate the host NF-κB signal when invading the host but also regulate this signal through its own encoded viral proteins. In this study, we find pH108R, an inner envelope protein of ASFV, can significantly downregulate NF-κB activation induced by IL-1β or TNFα. The overexpression of pH108R suppressed transcription of several proinflammatory cytokines such as IL-6, IL-8 induced by IL-1β or TNFα. Consistently, the levels of phosphorylated p65 and IκBα were decreased in pH108R overexpression cells after IL-1β and TNFα stimulation. In addition, transcriptome sequencing showed that it could significantly downregulate the expression of TNFα-induced immune and inflammatory genes in PK-15 cells. Collectively, our study indicates that ASFV pH108R markedly suppresses NF-κB activation stimulated by IL-1β or TNFα, clarifies the immunosuppressive activity of pH108R, and provides a new perspective for analyzing the immune escape of ASFV.