African swine fever virus protein-protein interaction identification prediction

Authors: FENSTER, JACOB - Oak Ridge Institute For Science And Education (ORISE); Azzinaro, Paul; Spinard Iii, Edward; Borca, Manuel; Gladue, Douglas

Submitted to: Viruses
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/12/2024
Publication Date: 7/20/2024
Citation: Fenster, J., Azzinaro, P.A., Spinard Iii, E.J., Borca, M.V., Gladue, D.P. 2024. African swine fever virus protein-protein interaction identification prediction. Viruses. 16(7). Article 1170. https://doi.org/10.3390/v16071170.
DOI: https://doi.org/10.3390/v16071170

Interpretive Summary: This report involves using prediction modeling using hi-throughput computing to predict proteins in the virus that interact with other proteins in the virus, which gives insight into the molecular complexes formed by viral proteins in the African swine fever virus. This information can be useful in other prediction models involving protein deletions in ASFV or subunit vaccines.

Technical Abstract: African swine fever virus (ASFV) is an often-deadly disease in swine and poses a threat to swine livestock and swine producers. With its complex genome containing more than 150 coding regions, developing affordable vaccines for this virus remains a challenge due to lack of basic knowledge about viral protein function and protein-protein interactions between viral proteins and between viral and host proteins. In this work, we identified ASFV-ASFV protein-protein interactions (PPIs), using artificial intelligence-powered protein structure prediction tools. We bench-marked Vaccinia virus, a widely studied nucleocytoplasmic large DNA virus, and found that it could identify gold standard PPIs that have been validated in vitro in a genome-wide computational screening. We applied this workflow to more than 18,000 pairwise combinations of ASFV proteins and were able to identify seventeen novel PPIs, many of which have corroborating experimental or bioinformatic evidence for their protein-protein interactions, further validating their relevance. Two protein-protein interactions, I267L and I8L, I267L__I8L, and B175L and DP79L, B175L__DP79L, are novel PPIs involving viral proteins known to modulate host immune response.