The multi-pronged entry of African swine fever virus: from host factors to therapeutic targets.

African swine fever (ASF), caused by the African swine fever virus (ASFV), remains one of the most devastating transboundary animal diseases worldwide, with case fatality rates reaching up to 100% in acute infections. Viral entry represents the first essential step in infection and is an ideal target for the development of vaccines and antiviral drugs. Recent studies have revealed that ASFV entry is not mediated by a single receptor or pathway. Instead, it involves multiple viral structural proteins, cellular attachment factors, endocytic routes, and intracellular trafficking regulators, which form a coordinated virus-host interaction network. In this review, we systematically summarize recent advances in ASFV multi-pathway invasion, including viral attachment, internalization, intracellular trafficking, uncoating, and membrane fusion. Additionally, we discuss several unresolved questions and highlight promising antiviral and genetic intervention strategies that target both viral components and host determinants. A comprehensive understanding of ASFV entry will provide the theoretical foundation for developing next-generation vaccines, antivirals, and disease-resistant pig populations.