Whole-genome analysis of bovine alphaherpesvirus 1 associated with abortion in a vaccinated U.S. cattle herd

Bovine alphaherpesvirus 1 (BoAHV1; family Orthoherpesviridae, taxon species Varicellovirus bovinealpha1)-a major cause of reproductive losses in cattle-establishes lifelong latency with periodic reactivation. Although vaccination reduces disease severity and abortion risk, BoAHV1 continues to circulate in cattle populations. Here, we report the whole-genome sequencing (WGS) of a BoAHV1 isolate recovered from fetal tissues associated with a last-trimester abortion in a vaccinated heifer herd. BoAHV1 was confirmed by quantitative PCR (qPCR) and virus isolation in Madin-Darby bovine kidney cells. The cell culture-isolated virus was subsequently sequenced using an Oxford Nanopore platform. Comparative genomic analysis using reference strain MH791339 identified 73 nucleotide variants (~0.12% of the genome), mostly located in the unique short (US) region. Multiple high-impact frameshift mutations were detected in several viral genes, including independent frameshifts in the infective cell protein 4 gene (bICP4) and moderate-impact variants in US3, a gene involved in immune modulation. Overall, genomic features were consistent with a wild-type BoAHV1.1 field strain and not compatible with known modified-live virus vaccine genomes. Our findings highlight the extent of genomic variability of BoAHV1 circulating in vaccinated cattle populations and demonstrate the value of WGS for resolving diagnostic questions related to abortion events and vaccine strain exclusion.