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

Salmonid alphavirus (SAV) poses a significant disease threat to aquaculture. Recently, new alphaviruses from several fish species have been discovered. However, little is known about their biology and diseases potential. Alphaviruses are considered to have originated from a marine environment; therefore, studying fish alphaviruses can inform on the evolutionary history of the genus. Contrary to many terrestrial alphaviruses, there are currently no experimentally-determined structures for aquatic alphaviruses, severely limiting their study. In this work, we harness the power of structural bioinformatics and AlphaFold to reconstruct an entire SAV virion, thereby revealing an exposed and distinctive α-helical feature in its E2 envelope protein. Using an integrative approach, we explore the sequence diversity and evolutionary conservation of this predicted feature and investigate the functional consequences of variations on viral fitness and virulence. This study provides a novel framework paving the way to better understand aquatic alphavirus pathogenicity and host species adaptation.