Molecular Analysis of Bovine Leukemia Virus Strains : Perspectives on Infection Control Strategies

Abstract

Bovine leukemia virus (BLV), a causative agent of enzootic bovine leukosis (EBL), is prevalent in cattle populations worldwide. While BLV infection is typically asymptomatic, a portion of infected animals progresses to persistent lymphocytosis or EBL. Beyond its oncogenic potential, BLV may exert broader impacts on the other effects such as exacerbation of mastitis. Therefore, controlling the spread of BLV remains a critical concern for the livestock industry. This study analyzed viral trait using infectious molecular clone isolated from BLV-infected cows in Japan, which is different approach compared with previous reports. First, analysis of full-length viral genomes from infected cattle revealed three genetic subgroups (A-C), with group A strains showing higher viral production than group C strains. In one farm, group A viruses were more prevalent and appeared to cluster spatially among tied cattle, suggesting that higher viral productivity enhances transmission. Next analysis identified a key nucleotide substitution at position 175 in the LTR (long terminal repeat) region as a determinant of viral replication efficiency. The LTR175C variant was associated with higher viral production and was increasingly detected over time within herds, suggesting ongoing replacement of the LTR175T genotype. Additionally, BLV isolates capable of inducing cellular transformation—a marker of oncogenic potential—were more frequently found in EBL-developed cattle. Notably, such high-pathogenicity strains shared distinct gene expression signatures despite genetic differences, suggesting convergent mechanisms of tumorigenesis. These findings indicate that specific viral genotypes are linked to both transmissibility and pathogenicity. Biomarkers such as the LTR175C mutation or host protein expression changes may be used to identify and control high-risk infections. This viral trait-based strategy offers a flexible and practical approach for controlling BLV spread and EBL onset, especially in high-prevalence herds where general measures are ineffective.