Genetic heterogeneity and pathogenetic mechanisms of bovine leukemia virus

Bovine leukemia virus is an RNA virus of the Retrovivridae family. It causes a chronic infectious disease in farm animals that poses a serious threat to global cattle farming. According to phylogenetic studies, the pathogen is classified into 12 genotypes. This comprehensive bioinformatic analysis featured new bovine leukemia virus isolates (n = 57) sampled from various regions of the Russian Federation with different epizootic situations. The analysis featured both new sequences and old samples from Russia available in the National Center for Biotechnology Information. This large-scale approach made it possible to cover all known genotypes. G4 genotype was associated with major amino acid substitutions in gp51 (T47A, A73P, R121H in epitope G; S56F in epitope H; I144T in ND2; D166G in CD8+). These substitutions provide a selective advantage through immune evasion mechanisms, including escape from humoral immunity, impaired T-cell recognition, and increased receptor affinity. G4 also correlated with rapid progression. The rapid replacement of G7 by G4 in the Tyumen Region and the general dominance of G4 in Russia were due to a more aggressive course of infection resulting from the genetic ability of the pathogen to adapt to the host immune system. The obtained data underscore the necessity of developing genotype-specific diagnostic systems and implementing routine molecular-genetic monitoring to control the spread of bovine leukemia virus. New data on genetic variability and its impact on genotype-phenotype correlations may help curb the infection.