Analysis of SalHV-1 Genes by Structure Prediction and Comparison Shows an Expanded Core Gene Set of the Order Herpesvirales

The order Herpesvirales contains three families, Orthoherpesviridae, Alloherpesviridae, and Malacoherpesviridae. The time since divergence of families from the common ancestor makes protein primary sequence comparison an insensitive tool for identifying common genes. Comparison of three-dimensional protein structures can reveal similarities that are not evident in primary sequences. Salmonid herpesvirus 1 (SalHV-1) is an alloherpesvirus. Complete sequencing of SalHV-1 VR-868 strain Winthrop by a combination of short- and long-read methods revealed 120 putative open reading frames (ORFs). BLAST search for similar protein sequences discovered five ORFs that encoded proteins with homologs in the orthoherpesviruses, including the major capsid protein, capsid triplex subunit 2, the catalytic subunit of the DNA polymerase, the helicase subunit of the helicase/primase complex, and the terminase ATPase subunit. An annotation of the ORFs of SalHV-1 was performed in which ORFs of SalHV-1 were modeled using AlphaFold3, and the models were used as prompts for structural similarity search using DALI and FoldSeek. Completion of this search strategy for the entire genome expanded the set of genes shared among the Herpesvirales to include additional proteins related to DNA replication and genome integrity, capsid assembly and genome packaging, and capsid nuclear egress. No homologs for any tegument proteins or proteins of the conserved entry apparatus of the Herpesviridae (gB, gH or gL) were discovered.