Deletion viral genome diversity amongst Bovine Viral Diarrhea Virus (BVDV) 1a and 1b strains

Authors: Holthausen, David; Bayles, Darrell; NEILL, JOHN - Retired ARS Employee; Dassanayake, Rohana; FALKENBERG, SHOLLIE - Auburn University; MENGHWAR, HARISH - Oak Ridge Institute For Science And Education (ORISE); Casas, Eduardo

Submitted to: Virology Journal
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/6/2025
Publication Date: N/A
Citation: N/A

Interpretive Summary: Bovine Viral Diarrhea Virus (BVDV) is a respiratory virus of major concern for the cattle industry. BVDV viruses are highly diverse and cause persistent infections and suppress the immune response of calves of pregnant cows. As part of the normal viral life cycle, viruses will create copies of their genome that have missing parts or deletions that get transmitted in viral particles. These genomes containing deletions cannot replicate by themselves but rely upon full length virus to create the machinery for viral replication. These deletion viral genomes or DelVGs help the virus regulate its life cycle and persist. In this study, we analyzed sequencing data from 2 subtypes of BVDV, BVDV1a and BVDV1b to understand if and what kinds of DelVGs BVDV generates and if there are any trends or differences between the two groups. Our results find that BVDV does naturally create genomes with deletions and that there are significant differences between different subtypes. We also found that in cell culture, different concentrations of BVDV impacts the deletion viral genomes that are generated.

Technical Abstract: Bovine Viral Diarrhea Virus (BVDV) is a pervasive respiratory pathogen of economic concern for the cattle industry. Deletion Viral Genomes (DelVGs) are naturally occurring products of the viral replication process by which viral genomic transcripts are generated with truncations of various size and cannot or severely impede self-replication. We used a bioinformatic pipeline to discover the presence of BVDV DelVGs. These deletion viral genomes were found by analyzing Illumina MiSeq reads from 74 BVDV1 field isolates from two closely related sub-genotypes, and in an in vitro passage of a BVDV1a virus at two different multiplicities of infection (MOI). Here we report that BVDV1a and BVDV1b sub-genotypes generate diverse species of DelVGs. After identifying DelVGs, we assessed their phylogenetic linkage to begin elucidating potential roles in the viral life cycle and persistence. BVDV1a viruses queried generate significantly more DelVGs, with 52% of 5’ and 3’ junctions occurring in the core/capsid (C) region and a major NS2-NS5B deletion species. In contrast, BVDV1b viruses generated significantly fewer DelVGs, especially reduced C region deletions. In vitro passage of the BVDV1a Singer virus demonstrates that MOI significantly impacts the generation of DelVGs with the higher MOI condition generating more DelVGs and a different deletion profile.