Work

African swine fever virus histone-like protein A104R subverts host antiviral defenses by suppressing the nuclear translocation of IRF3 and STAT1

Year: 2026

Type: article

Abstract: A104R of African swine fever virus (ASFV), putative histone-like protein, is known to be involved in essential processes such as viral DNA replication, repair, and transcription. Although it has been revealed that the deletion of A104R affects ASFV pathogenicity for live attenuated vaccine development, the molecular mechanism underlying those effects remains unclear. Here, we report a novel molecular mechanism of A104R that suppresses karyopherin-α (KPNA) mediated antiviral responses. A104R competitively bound to the major nuclear localization signal (NLS) region on KPNA3 and KPNA4, thereby disrupting their interaction with interferon regulatory factor 3 (IRF3). A104R also bound to the unique C terminal nonclassical NLS region of KPNA6 and competitively inhibited the interaction between KPNA6 and phosphorylated signal transducer and activator of transcription 1 (STAT1). Therefore, A104R inhibited the nuclear translocation of IRF3 and phosphorylated STAT1, thereby suppressing type I interferon (IFN) signalling and IFN-mediated antiviral responses. Consequently, ectopic expression of A104R enhanced DNA virus replication and suppressed IFN production by inhibiting the IRF3-mediated type I IFN signalling pathway and suppressed the interferon-β (IFN-β)-mediated antiviral responses. Taken together, these results highlight that A104R plays a dual role in suppressing IFN response and IFN-mediated antiviral responses. This mechanism provides new insight into the A104R induced ASFV pathogenesis, which provide a critical implication for a better understanding of the ASFV pathogenesis.

Source: Veterinary Research

DOI: 10.1186/s13567-026-01874-z