Functional Landscape of African Swine Fever Virus-Host and Virus-Virus Protein Interactions.

Viral replication fully relies on the host cell machinery, and physical interactions between viral and host proteins mediate key steps of the viral life cycle. Therefore, identifying virus-host protein-protein interactions (PPIs) provides insights into the molecular mechanisms governing virus infection and is crucial for designing novel antiviral strategies. In the case of the African swine fever virus (ASFV), a large DNA virus that causes a deadly panzootic disease in pigs, the limited understanding of host and viral targets hinders the development of effective vaccines and treatments. This review summarizes the current knowledge of virus-host and virus-virus PPIs by collecting and analyzing studies of individual viral proteins. We have compiled a dataset of experimentally determined host and virus protein targets, the molecular mechanisms involved, and the biological functions of the identified virus-host and virus-virus protein interactions during infection. Ultimately, this work provides a comprehensive and systematic overview of ASFV interactome, identifies knowledge gaps, and proposes future research directions.