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

Abstract

BACKGROUND: Bovine 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. RESULT: We 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. CONCLUSION:  This 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.