Association of haplotypes for SNPs in the LTR regions of bovine leukemia virus with hematological indices of cattle

Molecular typing of BLV samples isolated from Holsteinized Russian Black Pied cattle was carried out, and various cytofluorometric and morphological blood indices were examined. We performed the total count of white blood cells (WBC), lymphocyte (lymf), granulocyte (gran), monocyte (mon), red blood cell (RBC), hemoglobin (HGB), hematocrit (HTC), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red blood cell distribution width (RDW), platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), and platelet crit count (PCT). The LTR-region of BLV was haplotyped. Only viruses of haplotypes I (0.33±0.03) and III (0.67±0.03) of the eight possible were detected. The ratio of hematologically sick, healthy, and suspected carriers of BLV of haplotypes I and II was comparable with the results of other researchers. The numbers of leukocytes, erythrocytes and platelets in the blood of carriers of haplotype III exceeded the corresponding parameters of cattle affected by the virus of haplotype I. It is interesting to note that the difference in the hemolytic status of animals was manifested not only by the concentration of leukocytes as direct immune agents but also by the count of erythrocytes and platelets, which are not directly involved in the immune response. The number of particles of haplotype III of the BLV circulating in the blood of infected individuals exceeded that of the carriers of haplotype I. In this connection, an assumption was made about the evolutionary advantage of the more virulent haplotype III. However, the results of our own research in conjunction with the data of other scientists indicate that the high virulence of individual virus strains is a consequence of the tendency to implement the maximum possible intensity of the synthesis of virus particles but not of the high damaging effect alone. It is shown that high lethality is evolutionarily disadvantageous for viruses, since the extinction of the carrier as a biological species is fraught with the disappearance of the virus itself.

1. Acaite J., Tamosiunas V., Lukauskas K., Milius J., Pieskus J. The eradication experience of enzootic bovine leukosis from Lithuania. Prev. Vet. Med. 2007;82(1-2):83-89. DOI 10.1016/j.prevetmed. 2007.05.01.

2. Agol V.I. Nature of virus pathogenicity. Priroda = Nature. 2015;5: 3-10. (in Russian]

3. Barrick J.E., Yu D.S., Yoon S.H., Jeong H., Oh T.K., Schneider D., Lenski R.E., Kim J.F. Genome evolution and adaptation in a long-term experiment with Escherichia coli. Nature. 2009;461(7268):1243-1247. DOI 10.1038/nature08480.

4. Bateneva N.V. Features of the leukemic process in carriers of BLV genotypes 4 and 7. Innovatsii i Prodovolstvennaya Besopasnoct = Innovations and Food Safety. 2015;4(10):5-8. (in Russian)

5. Blood D.C., Henderson J.A., Radostits O.M. Veterinary Medicine: A textbook of the diseases of cattle, sheep, pigs, and horses. London: Balliere Tindall, 1979.

6. Buehring G.C., Philpott S.M., Choi K.Y. Humans have antibodies reactive with Bovine leukemia virus. AIDS Res. Hum. Retroviruses. 2003;19(12):1105-1113. DOI 10.1089/088922203771881202.

7. Debacq C., Sanchez Alcaraz M.T., Mortreux F., Kerkhofs P., Kettmann R., Willems L. Reduced proviral loads during primoinfection of sheep by Bovine Leukemia virus attenuated mutants. Retrovirology. 2004;1(31). DOI 10.1186/1742- 4690-1-31.

8. Elsworth P., Cooke B.D., Kovaliski J., Sinclair R., Holmes E.C., Strive T. Increased virulence of rabbit haemorrhagic disease virus associated with genetic resistance in wild Australian rabbits (Oryctolagus cuniculus). Virology. 2014;464- 465:415-423. DOI 10.1016/j.virol.2014.06.037.

9. Ernst L.K., Sulimova G.E., Orlova A.R. Peculiarities of distribution of Bola-A antigens and alleles of BoLA-DRB3 gene in black and white cattle due to association with leukemia. Russ. J. Genet. 1997; 33(1):73-80.

10. Fitzsimmons W.J., Woods R.J., McCrone J.T., Woodman A., Arnold J.J., Yennawar M., Evans R., Cameron C.E., Lauring A.S. A speed-fidelity trade-off determines the mutation rate and virulence of an RNA virus. PLoS Biol. 2018;16(6):e2006459. DOI 10.1371/journal.pbio.2006459.

11. Furió V., Garijo R., Durán M., Moya A., Bell J.C., Sanjuána R. Relationship between within-host fitness and virulence in the vesicular stomatitis virus: correlation with partial decoupling. J. Virol. 2012; 86(22):12228-12236. DOI 10.1128/ JVI.00755-12.

12. Gyles C. Should we be more concerned about bovine leukemia virus? Can Vet. J. 2016;57(2):115-116.

13. Juliarena M.A., Barrios C.N., Lützelschwab C.M., Esteban E.N., Gutiérrez S.E. Bovine leukemia virus: current perspectives. Vir. Adapt. Treat. 2017;(9):13-26. DOI 10.2147/ VAAT.S113947.

14. Kettmann R., Burny A., Callebaut I., Drogmans L., Mammerickx M., Willems L., Portetelle D. Bovine leukemia virus. Ed. J.A. Levy. The Retroviridae. New York: Plenum Press, 1994;39-82.

15. Kettmann R., Marbaix G., Cleuter Y., Portetelle D., Mammerickx M., Burny A. Genomic integration of bovine leukemia provirus and lack of viral RNA expression in the target cells of cattle with different responses to BLV infection. Leuk. Res. 1980;4(6):509-519.

16. Knapen K., Kerkhofs P., Mammerickx M. Eradication of enzootic bovine leukosis in Belgium: results of the mass detection on the national cattle population in 1989, 1990 and 1991. Ann. Med. Vet. 1993; 137:197-201.

17. Korboukh V.K., Lee C.A., Acevedo A., Vignuzzi M., Xiao Y., Arnold J.J., Hemperly S., Graci J.D., August A., Andino R., Cameron C.E. RNA Virus population diversity, an optimum for maximal fitness and virulence. J. Biol. Chem. 2014;289(43):29531-29544. DOI 10.1074/jbc.M114.592303.

18. Kozyreva N.G., Gulyukin M.I. The prevalence of cattle leukemia and genetic variants of its causative agent in livestock farms of the Central Federal District of the Russian Federation. Veterinariya Kubani = Veterinary of Kuban. 2017;6:4-9. (in Russian)

19. Lagarias M., Radke K. Transcriptional activation of bovine leukemia virus in blood cells from experimentally infected, asymptomatic sheep with latent infections. J. Virol. 1989;63:2099-2107.

20. Lakin G.F. Biometrics. Moscow: Vysshaya Shkola Publ., 1973. (in Russian) Lewin B. Genes IX. Oxford: Jones and Bartlett Publ., 2008.

21. Lezin A., Olindo S., Belrose G., Signate A., Cesaire R., Smadja D., Macallan D., Asquith B., Bangham C., Bouzar A., Gillet N., Defoiche J., Florins A., Verlaeten O., Burny A., Willems L. Gene activation therapy: from the BLV model to HAM/TSP patients. Front. Biosci. 2009; 1:205-215.

22. Markov A., Naimark E. Evolution. Classical Ideas in the Light of New Discoveries. Moscow: ACT: CORPUS Publ., 2015. (in Russian)

23. Merezak C., Pierreux C., Adam E., Lemaigre F., Rousseau G.G., Calomnie C., Van Lint C., Christophe D., Kerkhofs P., Burny A., Kettmann R., Willems L. Suboptimal enhancer sequences are required for efficient bovine leukemia virus propagation in vivo: implications for viral latency. J. Virol. 2001;75:6977- 6988. DOI 10.1128/JVI.75.15. 6977-6988.2001.

24. Mischenko V.A., Petrova O.N., Karaulov A.K., Mischenko A.V. Problems of Bovine Leukemia. Vladimir, 2018. (in Russian) Moelling K. Viruses: More Friends Than Foes. Singapore: World Scientific Publ., 2016. DOI 10.1142/10230.

25. Novikova M.V., Borovoy V.N., Barsukov Yu.I., Kolomytsev S.A. Epizootic situation with socially significant and highly infectious diseases of animals in the Russian Federation in 2017. Business Partner (Agriculture). Annual Handbook for Managers and Professionals in AIC, 2018. Available at: mvet/epizooticheskaya-situatsiya-po-sotsialno-znachimym-i-osobo-opasnym boleznyam-zhivotnykh. (in Russian)

26. Nuotio L., Rusanen H., Sihvonen L., Neuvonen E. Eradication of enzootic bovine leukosis from Finland. Prev. Vet. Med. 2003;59(1-2): 43-49.

27. Polat M., Takeshima S., Aida Y. Epidemiology and genetic diversity of bovine leukemia virus. Virol. J. 2017;14:209. DOI 10.1186/s12985-017-0876-4.

28. Smirnov P.N. The Disease of the Century: Bovine Leukemia. Novosibirsk, 2007. (in Russian)

29. Smirnov P.N., Bateneva N.V., Belyavskaya V.A. Genotypic diversity of bovine leukemia virus in the Novosibirsk and Krasnodar regions. Vestnik Novosibirskogo Gosudarstvennogo Agrarnogo Universiteta = Bulletin of the Novosibirsk State Agrarian University. 2011;2(18):81-83. (in Russian)

30. Smirnov P.N., Bateneva N.V., Knyazev S.P., Khripko Yu.I., Skachkov A.S. Method for the study of nucleotide sequences BVL. Mezhdunarodnyy Nauchno-Issledovatelskiy Zhurnal = International Research Journal. 2015;7(38):95-98. (in Russian)

31. Smirnov Yu.P., Suvorova I.L., Gryazeva N.A. Dynamics of the epizootic process of bovine leukemia in the Kirov region and the effectiveness of anti-leukemia measures. Agrarnaya Nauka Evro-Severo-Vostoka = Agricultural Science of the Euro-North-East. 2015;1(44): 60-65. (in Russian)

32. Syurin V.N., Samuylenko A.Ya., Solov’ev B.V., Fomina N.V. Viral Diseases of Animals. Moscow, All-Russia Research and Technology Institute of Bioindustry, 2001. (in Russian)

33. Zhivotovskiy L.A. Populational Biometry. Moscow: Nauka Publ., 1991. (in Russian)