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

## TL;DR

Researchers used structural bioinformatics to reconstruct a salmonid alphavirus, revealing a unique protein feature linked to its virulence.

## Contribution

The first in silico reconstruction of a salmonid alphavirus virion and identification of a conserved E2 α-helix associated with virulence.

## Key findings

- An exposed α-helix and 7-8-9 motif were discovered at the E2 protein N-terminus.
- The E2 α-helix is conserved among aquatic alphaviruses.
- Mutations in the E2 N-terminus affect viral fitness and virulence.

## Abstract

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 pathogenicity. 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 framework paving the way to better understand aquatic alphavirus pathogenicity and host species adaptation.

•Reconstruction of an entire salmonid alphavirus virion by structural bioinformatics•Discovery of an exposed α-helix and 7-8-9 triplet motif at E2 protein N-terminus•The E2 α-helix is a conserved feature of aquatic alphaviruses•Mutations in E2 N-terminus alter viral fitness in vitro and virulence in vivo

Reconstruction of an entire salmonid alphavirus virion by structural bioinformatics

Discovery of an exposed α-helix and 7-8-9 triplet motif at E2 protein N-terminus

The E2 α-helix is a conserved feature of aquatic alphaviruses

Mutations in E2 N-terminus alter viral fitness in vitro and virulence in vivo

Virology; structural biology; bioinformatics