African Swine Fever Virus pD345L Suppresses JAK-STAT Signaling by Selectively Triggering STAT1 Degradation

African swine fever (ASF) is a highly lethal viral disease of pigs caused by the African swine fever virus (ASFV). The mortality rate is nearly 100%. Currently, it is known that the ASFV has a complex structure, and its genome encodes various immune escape proteins. However, the pathogenic mechanism of ASFV remains to be studied. This study found that ASFV pD345L significantly inhibits the activation of the ISRE promoter triggered by interferon (IFN) β and the production of downstream IFN-stimulated genes (ISG). We further reveal that pD345L may degrade STAT1 via the Autophagy pathway and impede its nuclear translocation; this inhibitory effect is closely associated with its exonuclease activity. Our research results have clarified the impact of ASFV pD345L on the JAK/STAT signaling pathway, expanding our understanding of the inhibitory effect of ASFV-encoded proteins on the host's innate immunity, and to some extent, contributing to the development of an African swine fever vaccine.