Genomic characterization and evolutionary analysis of three bovine viral diarrhea virus 1b strains from Taiwan, highlighting genomic evidence of cytopathic evolution.

backgroundBovine viral diarrhea virus type 1 (BVDV-1) affects cattle health and productivity worldwide. A nationwide surveillance of BVDV-1 showed persistent circulation in Taiwan in past decade. It exists in two biotypes-noncytopathic (ncp) and cytopathic (cp), which differ in clinical presentation and pathogenic mechanisms. Despite its prevalence in Taiwan, the genomic features that distinguish these biotypes remain poorly characterized.

resultWe recently identified two Taiwanese BVDV-1 in clinical samples, namely BV27 and BV236, from a beef cattle without clinical symptom and a dying dairy cow, respectively, in 2023. Whole genome sequencing using the Illumina NovaSeq X Plus platform revealed genome lengths of 12,207 bp for BV27 and 15,047 bp for BV236. Notably, BV236 derived from cattle exhibiting severe diarrhea prior to death contained a duplicated NS3-NS4A-partial NS4B region and a 240 bp insertion of ubiquitin C gene derived from bovine, a feature commonly associated with causing severe symptom and cytopathic biotype. Moreover, a long-range PCR further revealed the coexistence of two viral genomes within the same sample, one carrying these genomic modifications and one lacking them. Phylogenetic analysis classified both viruses as BVDV-1b, the same subgenotype as 18H17, a previously reported Taiwanese strain. Of note, haplotype network analysis indicated that BV27 and BV236 are genetically distinct from 18H17, which indicated multiple strains of BVDV-1b circulating in Taiwan possible occurred through transboundary transportation.

conclusionThis study provides both clinical and genomic evidence on Taiwanese BVDVs. We identified two genetically distinct BVDV-1b strains, and although phenotypic assays were not performed, one strain (BV236) exhibited genomic hallmarks of cytopathogenic evolution that corresponded with severe respiratory symptoms. These findings suggest the coexistence of multiple BVDV-1b lineages in Taiwan and highlight their genomic diversity and potential pathogenic evolution. While based solely on genomic data, this work establishes a foundation for understanding BVDV diversity in Taiwan and underscores the need for continued molecular surveillance and future functional studies to clarify the role of these genomic features in cytopathogenicity.