Yekaterinburg, Russian Federation
Yekaterinburg, Russian Federation
Yekaterinburg, Russian Federation
Yekaterinburg, Russian Federation
Yekaterinburg, Russian Federation
Yekaterinburg, Russian Federation
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.
Bovine leukemia virus, bioinformatic analysis, genotype G4, gp51, amino acid substitutions, env gene, epitope, epizootiology, virus evolution, diagnostics
1. Brujeni GN, Houshmand P, Soufizadeh P. Bovine leukemia virus: A perspective insight into the infection and immunity. Iranian Journal of Veterinary Research. 2023;24(4):290–300. https://doi.org/10.22099/IJVR.2023.48236.7023
2. Kuczewski A, Mason S, Orsel K, van der Meer F. Pilot implementation of a newly developed bovine leukemia virus control program on 11 Alberta dairy farms. Journal of Dairy Science. 2021;104(4):4549–4560. https://doi.org/10.3168/jds.2020-19251
3. Lv G, Wang J, Lian S, Wang H, Wu R. The global epidemiology of bovine leukemia virus: Current trends and future implications. Animals. 2024;14(2):297. https://doi.org/10.3390/ani14020297
4. Pereira JG, Silva CA, Silva LD, Lima CAA, do Rosário CJRM, et al. Diagnosis and phylogenetic analysis of bovine leukemia virus in dairy cattle in northeastern Brazil. Frontiers in Veterinary Science. 2022;9:1080994. https://doi.org/10.3389/fvets.2022.1080994
5. Zhao Y, Wang J, Chen J, Chen Y, Huet C, et al. Bovine leukemia virus: Origin, prevalence, phylogenetic diversity, risk factors, and strategies for control. Animals. 2025;15(9):1344. https://doi.org/10.3390/ani15091344
6. Poryvaeva AP, Pechura EV, Petrova OG, Bezborodova NA, Lysova YaYu, et al. The effectiveness of scientifically based monitoring programs and therapeutic and preventive measures for controlled infectious diseases of animals. International Journal of Veterinary Medicine. 2023;(4):96–110. (In Russ.) https://doi.org/10.52419/issn2072-2419.2023.4.96
7. Shrestha S, Orsel K, Barkema HW, Martins L, Shrestha S, et al. Effects of bovine leukemia virus seropositivity and proviral load on milk, fat, and protein production of dairy cows. Journal of Dairy Science. 2024;107(1):530–539. https://doi.org/10.3168/jds.2023-23695
8. Johnston ER, Albritton LM, Radke K. Envelope proteins containing single amino acid substitutions support a structural model of the receptor-binding domain of bovine leukemia virus surface protein. Journal of Virology. 2002;76(21):10861–10872. https://doi.org/10.1128/jvi.76.21.10861-10872.2002
9. Tomé-Poderti L, Olivero-Deibe N, Carrión F, Portela MM, Obal G, et al. Characterization and application of recombinant bovine leukemia virus env protein. International Journal of Scientific Reports. 2024;14:12190. https://doi.org/10.1038/s41598-024-62811-8
10. Callebaut I, Voneche V, Mager A, Fumière O, Krchnak V, et al. Mapping of B-neutralizing and T-helper cell epitopes on the bovine leukemia virus external glycoprotein gp51. Journal of Virology. 1993;67(9):5321–5327. https://doi.org/10.1128/JVI.67.9.5321-5327.1993
11. Zhao X, Buehring GC. Natural genetic variations in bovine leukemia virus envelope gene: Possible effects of selection and escape. Virology. 2007;366(1):150–165. https://doi.org/10.1016/j.virol.2007.03.058
12. Bai L, Takeshima S, Isogai E, Kohara J, Aida Y. Novel CD8+ cytotoxic T cell epitopes in bovine leukemia virus with cattle. Vaccine. 2015;33(51):7194–7202. https://doi.org/10.1016/j.vaccine.2015.10.128
13. de Brogniez A, Bouzar AB, Jacques JR, Cosse JP, Gillet N, et al. Mutation of a single envelope N-Linked glycosylation site enhances the pathogenicity of bovine leukemia virus. Journal of Virology. 2015;89(17):8945–8956. https://doi.org/10.1128/JVI.00261-15
14. Murakami H, Uchiyama J, Suzuki C, Nikaido S, Shibuya K, et al. Variations in the viral genome and biological properties of bovine leukemia virus wild-type strains. Virus Research. 2018;253:103–111. https://doi.org/10.1016/j.virusres.2018.06.005
15. de Brogniez A, Mast J, Willems L. Determinants of the bovine leukemia virus envelope glycoproteins involved in infectivity, replication and pathogenesis. Viruses. 2016;8(4):88. https://doi.org/10.3390/v8040088
16. Pluta A, Rola-Łuszczak M, Hoffmann FG, Donnik I, Petropavlovskiy M, et al. Genetic variability of bovine leukemia virus: Evidence of dual infection, recombination and quasi-species. Pathogens. 2024;13(2):178. https://doi.org/10.3390/pathogens13020178
17. Olaya-Galán NN, Corredor-Figueroa AP, Velandia-Álvarez S, Vargas-Bermudez DS, Fonseca-Ahumada N, et al. Evidence of bovine leukemia virus circulating in sheep and buffaloes in Colombia: Insights into multispecies infection. Archives of Virology. 2022;167:807–817. https://doi.org/10.1007/s00705-021-05285-7
18. Blanco R, Quezada-Romegialli C, Muñoz JP. Bovine leukemia virus and human breast cancer: A review of clinical and molecular evidence. Viruses. 2025;17(3):324. https://doi.org/10.3390/v17030324
19. Khan Z, Abubakar M, Arshed MJ, Aslam R, Sattar S, et al. Molecular investigation of possible relationships concerning bovine leukemia virus and breast cancer. Scientific Reports. 2022;12:4161. https://doi.org/10.1038/s41598-022-08181-5
20. Polat M, Takeshima SN, Aida Y. Epidemiology and genetic diversity of bovine leukemia virus. Journal of Virology. 2017;14:209. https://doi.org/10.1186/s12985-017-0876-4
21. Bai L, Soya M, Ichikawa M, Matsuura R, Arimura Y, et al. Antigenicity of subregions of recombinant bovine leukemia virus (BLV) glycoprotein gp51 for antibody detection. Journal of Virological Methods. 2023;311;114644. https://doi.org/10.1016/j.jviromet.2022.114644
22. Ramalho GC, Silva MLCR, Falcão BMR, Limeira CH, Nogueira DB, et al. High herd-level seroprevalence and associated factors for bovine leukemia virus in the semi-arid Paraíba state, Northeast Region of Brazil. Preventive Veterinary Medicine. 2021;190:105324. https://doi.org/10.1016/j.prevetmed.2021.105324
23. Donnik IM, Gulyukin MI, Busol VA, Kovalenko LV, Kovalenko AM Bovine leukemia virus infection – diagnostics, eradication, and anthropozoonotic potential (background) (review). Agricultural Biology. 2021;56(2):230–244. (In Russ.) https://doi.org/10.15389/agrobiology.2021.2.230eng
24. Marawan MA, Alouffi A, Tokhy SE, Badawy S, Shirani I, et al. Bovine leukaemia virus: Current epidemiological circumstance and future prospective. Viruses. 2021;13(11):2167. https://doi.org/10.3390/v13112167
25. Suzuki A, Chapman R, Douglass N, Carulei O, van Rensburg J, et al. Phylogenetic analysis of South African bovine leukaemia virus (BLV) isolates. Viruses. 2020;12(8):898. https://doi.org/10.3390/v12080898
26. Maezawa M, Fujii Y, Akagami M, Kawakami J, Inokuma H, et al. Phylogenetic analysis based on whole genome sequence of bovine leukemia virus in cattle under 3 years old with enzootic bovine leukosis. PLoS One. 2023;18(1):e0279756. https://doi.org/10.1371/journal.pone.0279756
27. Pluta A, Rola-Luszczak M, Kubis P, Balov S, Moskalik R, et al. Molecular characterization of bovine leukemia virus from Moldovan dairy cattle. Archives of Virology. 2017;162(6):1563–1576. https://doi.org/10.1007/s00705-017-3241-4
28. Rola-Łuszczak M, Sakhawat A, Pluta A, Ryło A, Bomba A, et al. Molecular characterization of the env gene of bovine leukemia virus in cattle from Pakistan with NGS-Based evidence of virus heterogeneity. Pathogens. 2021;10(7):910. https://doi.org/10.3390/pathogens10070910
29. Baboshko DA, Gashnikova NM, Totmenin AV, Nefedova AA, Osipova IP, et al. Genetic diversity of BLV, common in the territory of the Kochenevsky district of the Novosibirsk region. Veterinariya i kormleniye. 2022;2:17–19. (In Russ.) https://doi.org/10.30917/ATT-VK-1814-9588-2022-2-4
30. Donnik IM, Petropavlovsky MV, Makutina VA, Gulyukin MI, Barsukov YuI. The current bovine leukemia spread situation in the Russian Federation. Veterinariya. 2024;(11):18–22. (In Russ.) https://doi.org/10.30896/0042-4846.2024.27.11.18-22
31. Sultanov A, Rola-Łuszczak M, Mamanova S, Ryło A, Osiński Z, et al. Molecular characterization of bovine leukemia virus with the evidence of a new genotype circulating in cattle from Kazakhstan. Pathogens. 2022;11(2):180. https://doi.org/10.3390/pathogens11020180
32. Lee E, Kim EJ, Joung HK, Kim BH, Song JY, et al. Sequencing and phylogenetic analysis of the gp51 gene from Korean bovine leukemia virus isolates. Journal of Virology. 2015;12:64. https://doi.org/10.1186/s12985-015-0286-4
33. Úsuga-Monroy C, Díaz FJ, González-Herrera LG, Echeverry-Zuluaga JJ, López-Herrera A. Phylogenetic analysis of the partial sequences of the env and tax BLV genes reveals the presence of genotypes 1 and 3 in dairy herds of Antioquia, Colombia. VirusDisease. 2023;34:483–497. https://doi.org/10.1007/s13337-023-00836-9
34. Yang Y, Chen L, Dong M, Huang W, Hao X, et al. Molecular characterization of bovine leukemia virus reveals existence of genotype 4 in Chinese dairy cattle. Journal of Virology. 2019;16(1):108. https://doi.org/10.1186/s12985-019-1207-8
35. Rola-Łuszczak M, Pluta A, Olech M, Donnik I, Petropavlovskiy M, et al. The molecular characterization of bovine leukaemia virus isolates from Eastern Europe and Siberia and its impact on phylogeny. PLoS One. 2013;8(3):e58705. https://doi.org/10.1371/journal.pone.0058705
36. Bruck C, Rensonnet N, Portetelle D, Cleuter Y, Mammerickx M, et al. Biologically active epitopes of bovine leukemia virus glycoprotein gp51: Their dependence on protein glycosylation and genetic variability. Virology. 1984;136(1):20–31. https://doi.org/10.1016/0042-6822(84)90244-7
37. Mamoun RZ, Morisson M, Rebeyrotte N, Busetta B, Couez D, et al. Sequence variability of bovine leukemia virus env gene and its relevance to the structure and antigenicity of the glycoproteins. Journal of Virology. 1990;64(9):4180–4188. https://doi.org/10.1128/jvi.64.9.4180-4188.1990
38. Rola-Łuszczak M, Grabowska A, Szewczyk B, Kuźmak J. Baculovirus expression and potential diagnostic application of the gp51 envelope glycoprotein of genetic mutants of the bovine leukaemia virus. Journal of Veterinary Research. 2019;63(1):1–6. https://doi.org/10.2478/jvetres-2019-0020
39. Wu X, Li T, Jiang R, Yang X, Guo H, et al. Targeting MHC-I molecules for cancer: Function, mechanism, and therapeutic prospects. Molecular Cancer. 2023;22:194. https://doi.org/10.1186/s12943-023-01899-4
40. Moratorio G, Fischer S, Bianchi S, Tomé L, Rama G, et al. A detailed molecular analysis of complete bovine leukemia virus genomes isolated from B-cell lymphosarcomas. Veterinary Research. 2013;44:19. https://doi.org/10.1186/1297-9716-44-19
41. Gatot JS, Callebaut I, van Lint C, Demonté D, Kerkhofs P, et al. Bovine leukemia virus SU protein interacts with zinc, and mutations within two interacting regions differently affect viral fusion and infectivity in vivo. Journal of Virology. 2002;76(16):7956–7967. https://doi.org/10.1128/jvi.76.16.7956-7967.2002
42. Adomako RA, Owusu MB, Oberdick RK, Senyah K, Asare P, et al. Zn (II) affinity and structural conformations of 2His-2Cys zinc finger-like motif peptide determined by ion mobility-mass spectrometry and PM6 molecular modeling. Journal of Mass Spectrometry. 2025;60(3):e5113. https://doi.org/10.1002/jms.5113
43. Donnik IM, Petropavlovsky MV. Cattle leukosis: Modern approach. Dairy cattle breeding. 2022;S2:57–59. (In Russ.) https://doi.org/10.25701/ZZR.2022.03.03.011
44. Petersen MI, Suarez Archilla G, Miretti MM, Trono KG, Carignano HA Whole-transcriptome analysis of BLV-infected cows reveals downregulation of immune response genes in high proviral loads cows. Frontiers in Veterinary Science. 2025;12:1550646. https://doi.org/10.3389/fvets.2025.1550646
