In silico reconstruction of a salmonid alphavirus virion reveals distinctive molecular features implicated in virulence

In an article published in the journal iScience, researchers from INRAE units Virologie et Immunologie Moléculaires (VIM), Université Paris-Saclay, UVSQ, and Génétique Animale et Biologie Intégrative (GABI), Université Paris-Saclay, AgroParisTech, took up the challenge to reconstruct in silico the entire structure of an SAV virion using a structural bioinformatics approach based on artificial intelligence. The structure of viral proteins were predicted using AlphaFold and were successfully assembled in higher-order complexes obeying to an icosahedral symmetry. These powerful approaches led to the discovery of a singular α-helical secondary structure at the N-terminus of the surface exposed E2 envelope protein. Taking an integrative approach, the study explored the diversity of sequences and evolutionary conservation of this α-helix as well as the functional consequences of variations on viral fitness and virulence. These advances paves the way to a better understanding of the pathogenicity of aquatic alphaviruses and their adaptation to their host species.