Host-pathogen interactions in African swine fever: From viral entry to systemic disease progression

African swine fever virus (ASFV), a large and complex double-stranded DNA virus, is the etiological agent of African swine fever (ASF). ASF is a highly contagious and lethal hemorrhagic disease in domestic swine, which poses a persistent threat to global swine production and food security. Despite extensive research efforts, the development of safe and effective vaccines or antivirals remains elusive. This is largely attributable to the incomplete understanding of the intricate replication cycle of ASFV and its multifaceted evasion of host defenses. The mechanisms by which ASFV orchestrates widespread damage within the host to maintain its highly efficient replication and evade host defenses remain a key question in the field. In this comprehensive review, we aim to synthesize the current understanding of the key mechanisms underlying ASFV replication and immune evasion, as well as the associated host damage. By integrating these insights with the clinical and pathological features of ASF, we seek to deepen our comprehension of the viral pathogenic mechanisms and highlight existing research gaps. Ultimately, our goal is to provide valuable guidance for future endeavors in vaccine and antiviral drug development.