Host–virus immune crosstalk and immune evasion mechanisms of African swine fever virus: recent progress and translational implications

Abstract African swine fever (ASF), caused by African swine fever virus (ASFV), is an acute and highly contagious disease characterized by high fatality and rapid transmission and poses severe threats to the global pig industry. As a complex nucleocytoplasmic large DNA virus (NCLDV), ASFV has evolved sophisticated and highly efficient immune evasion strategies. It remodels the host immune microenvironment through multiple molecular mechanisms, inhibiting both innate and adaptive immune surveillance to sustained intracellular replication. Such potent immune evasion capacity constitutes the primary bottleneck restricting the development of safe and effective commercial vaccines. In this review, we summarize recent research progress and systematically delineate host innate and adaptive immune networks during ASFV infection. This review focuses on the core immune evasion mechanisms of ASFV, including the suppression of type I interferon production by antagonizing pattern recognition receptors (such as cGAS-STING and Toll-like receptor cascades) and the Janus kinase-signal transducer and activator of transcription (JAK-STAT) axis, the bidirectional regulation of nuclear factor kappa B (NF-κB) signaling and the NLR family pyrin domain containing 3 (NLRP3) inflammasome to manipulate inflammatory responses and programmed cell death, and the impairment of antigen presentation and lymphocyte activation. Moreover, this review elaborates on the temporal dynamics and synergistic effects of these immune evasion mechanisms, aiming to provide systematic theoretical insights into deciphering ASFV pathogenesis and facilitating novel vaccine development and anti-ASFV drug discovery.