African swine fever virus E120R protein inhibits interferon-β production by interacting with IRF3 to block its activation

African swine fever is a devastating disease of swine caused by African swine fever virus (ASFV). The pathogenesis of the disease remains largely unknown, leaving the uncontrolled spreading of the disease in many countries and regions. Here, we identified the E120R, a structural protein of ASFV, as a key virulent factor and late phase expression protein of the virus. E120R revealed an activity to suppress host antiviral response through blocking IFN-β production, and the 72-73 amino acid sites in the C-terminal domain were essential for this function. E120R interacted with the interferon regulatory factor 3 (IRF3) and interfered with the recruitment of IRF3 to TBK1, which in turn suppressed IRF3 phosphorylation, decreasing interferon production. The recombinant mutant ASFV was further constructed to confirm the claimed mechanism. The ASFV lacking the complete E120R region could not be rescued, whereas the virus could tolerate the deletion of the 72nd and 73rd residuals in the E120R (ASF...