African swine fever virus early protein pI73R suppresses the type-I IFN promoter activities

Abstract

African swine fever virus is known to suppress type-I interferon (IFN) responses. The main objective of this study was to screen early-expressed viral genes for their ability to suppress IFN production. Out of 16 early genes examined, I73R exhibited robust suppression of cGAS-STING-induced IFN-β promoter activities, impeding the function of both IRF3 and NF-κB transcription factors. As a result, I73R obstructed IRF3 nuclear translocation following the treatment of cells with poly(dA:dT), a strong inducer of the cGAS-STING signaling pathway. Although the I73R protein exhibits structural homology with the Zα domain binding to the left-handed helical form of DNA known as Z-DNA, its ability to suppress cGAS-STING induction of IFN-β was independent of Z-DNA binding activity. Instead, the α3 and β1 domains of I73R played a significant role in suppressing cGAS-STING induction of IFN-β. These findings offer insights into the protein's functions and support its role as a virulence factor.