Functional Landscape of African Swine Fever Virus–Host and Virus–Virus Protein Interactions

Abstract

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.

Exploring type I interferon pathway: virulent vs. attenuated strain of African swine fever virus revealing a novel function carried by MGF505-4R

“…Altogether, this emphasizes the evolution of ASFV to encode numerous viral proteins with redundant functions in immune evasion. Collectively, deciphering molecular virus-host protein interactions and mechanisms underlying the control of the innate immune response by ASFV will constitute an important theoretical basis to reveal new factors of virulence and develop future rationally designed ASFV vaccines ( 75 ).…”

Genetic Variations of African Swine Fever Virus: Major Challenges and Prospects

“…ASFV has a large genome, which may be a significant factor contributing to this phenomenon. When certain proteins are deleted in a viral strain, complex interactions between the remaining proteins and genes are triggered, orchestrating a compensatory response [ 83 ]. This mechanism, similar to a complex self-regulation process, ensures the sustained operational integrity of the virus despite genetic deficits.…”

A genome-wide CRISPR/Cas9 knockout screen identifies TMEM239 as an important host factor in facilitating African swine fever virus entry into early endosomes

“…The ASF global epidemic poses a serious threat to global food security and livestock health [ 8 ]. Antiviral therapeutics or vaccines against ASF are lacking, a predicament that is largely attributed to our limited understanding of ASFV etiology and ASFV-host interactions [ 9 , 10 ].…”