Structural characteristics of the bovine leukemia virus genome: A mini review
https://doi.org/10.21323/2618-9771-2023-6-3-283-287
Abstract
Enzootic bovine leukemia is an infectious disease with a chronic course caused by an RNA‑containing virus of the genus Deltaretrovirus. Despite the implementation of various programs for the elimination of leukemia, the disease is still widespread on the planet and continues to cause significant economic damage. A large proportion of BLV‑infected cattle remain to be asymptomatic carriers of the virus, which complicates diagnosis and contributes to the spread of the disease in the herd. The structure of the BLV genome is generally typical of retroviruses. It consists of genes encoding structural proteins, viral enzymes and regulatory elements flanked on both sides by identical long terminal repeats. The enzyme and structural protein coding genes (gag, pro, pol, and env) play a crucial role in the life cycle of the virus, influencing its infectivity and virion production. The tax and rex regulatory genes regulate viral transcription, export of transcripts from the nucleus to the cytoplasm, and disease progression. The increase in the number of copies of proviral DNA occurs mainly not due to the functioning of the virus reverse transcriptase, but because of clonal reproduction of the affected subpopulations of B‑cells, mainly CD5+ IgM+. This feature provides increased genetic stability of the BLV virus. These properties of the viral genome allow the development of a variety of PCR test systems. The widespread implementation of such systems enables the detection of carriers of the disease at early stages, which should contribute to the effective implementation of national programs to eradicate bovine leukemia.
Supporting agencies: The article was prepared within the framework of research on the state task of Research and Development No. FNSS-2022-0006 of the AllRussian Research Institute of Dairy Industry.
About the Author
O. Yu. Fomenko
All-Russian Dairy Research Institute
Russian Federation
Russian Federation
Oleg Yu. Fomenko, Candidate of Biological Sciences, Senior Researcher, Central Laboratory of Microbiology
35/7, Lyusinovskaya str., 115093, Moscow
Tel.: +7–904–211–01–75
References
1. Achachi, A., Florins, A., Gillet, N., Debacq, C., Urbain, P., Foutsop, G. M. et al. (2005). Valproate activates bovine leukemia virus gene expression, triggers apoptosis, and induces leukemia/lymphoma regression in vivo. Proceedings of the National Academy of Sciences of the United States of America, 102(29), 10309–10314. https://doi.org/10.1073/pnas.0504248102
2. Miller, J. M., Miller, L. D., Olson, C., Gillette, K. G. (1969). Virus-like particles in phytohemagglutinin-stimulated lymphocyte cultures with reference to bovine lymphosarcoma. Journal of the National Cancer Institute, 43(6), 1297–1305. https://doi.org/10.1093/jnci/43.6.1297
3. Kettmann, R., Portetelle, D., Mammerickx, M., Cleuter, Y., Dekegel, D., Galoux, M. et al. (1976). Bovine leukemia virus: An exogenous RNA oncogenic virus. Proceedings of the National Academy of Sciences of the United States of America, 73(4), 1014–1018. https://doi.org/10.1073/pnas.73.4.1014
4. Murakami, H., Yamada, T., Suzuki, M., Nakahara, Y., Suzuki, K., Sentsui, H. (2011). Bovine leukemia virus integration site selection in cattle that develop leukemia. Virus Research, 156(1–2), 107–112. https://doi.org/10.1016/j.virusres.2011.01.004
5. Hron, T., Elleder, D., Gifford, R. J. (2019). Deltaretroviruses have circulated since at least the Paleogene and infected a broad range of mammalian species. Retrovirology, 16, Article 33. https://doi.org/10.1186/s12977–019–0495–9
6. Aida, Y., Okada, K., Amanuma, H. (1993). Phenotype and ontogeny of cells carrying a tumor-associated antigen that is expressed on bovine leukemia virusinduced lymphosarcoma. Cancer Research, 53(2), 429–437.
7. Sagata, N., Yasunaga, T., Tsuzuku-Kawamura, J., Ohishi, K., Ogawa, Y., Ikawa, Y. (1985). Complete nucleotide sequence of the genome of bovine leukemia virus: Its evolutionary relationship to other retroviruses. Proceedings of the National Academy of Sciences of the United States of America, 82(3), 677–681. https://doi.org/10.1073/pnas.82.3.677
8. Polat, M., Takeshima, Sn., Aida, Y. (2017). Epidemiology and genetic diversity of bovine leukemia virus. Virology Journal, 14, Article 209. https://doi.org/10.1186/s12985–017–0876–4
9. Moratorio, G., Fischer, S., Bianchi, S., Tomé, L., Rama, G., Obal, G. et al. (2013). A detailed molecular analysis of complete Bovine Leukemia Virus genomes isolated from B-cell lymphosarcomas. Veterinary Research, 44, Article 19. https://doi.org/10.1186/1297–9716–44–19
10. Nguyên, T. L., de Walque, S., Veithen, E., Dekoninck, A., Martinelli, V., de Launoit, Y. et al. (2007). Transcriptional regulation of the bovine leukemia virus promoter by the cyclic AMP-response element modulator tau isoform. Journal of Biological Chemistry, 282(29), 20854–20867. https://doi.org/10.1074/jbc.M703060200
11. Calomme, C., Dekoninck, A., Nizet, S., Adam, E., Nguyên, T.L., Van Den Broeke, A. et al. (2004). Overlapping CRE and E box motifs in the enhancer sequences of the bovine leukemia virus 5’ long terminal repeat are critical for basal and acetylation-dependent transcriptional activity of the viral promoter: Implications for viral latency. Journal of Virology, 78(24), 13848–13864. https://doi.org/10.1128/JVI.78.24.13848–13864.2004
12. Xiao J., Buehring G. C. (1998). In vivo protein binding and functional analysis of cis-acting elements in the U3 region of the bovine leukemia virus long terminal repeat. Journal of Virology, 72(7), 5994–6003. https://doi.org/10.1128/JVI.72.7.5994–6003.1998
13. Dekoninck, A., Calomme, C., Nizet, S., de Launoit, Y., Burny, A., Ghysdael, J. et al. (2003). Identification and characterization of a PU.1/Spi-B binding site in the bovine leukemia virus long terminal repeat. Oncogene, 22(19), 2882–2896. https://doi.org/doi:10.1038/sj.onc.1206392
14. Derse, D. (1987). Bovine leukemia virus transcription is controlled by a virusencoded transacting factor and by CIS-acting response elements. Journal of Virology, 61(8), 2462–2471. https://doi.org/10.1128/jvi.61.8.2462–2471.1987
15. Maezawa, M., Fujii, Y., Akagami, M., Kawakami, J., Inokuma, H. (2023). Phylogenetic analysis based on whole genome sequence of bovine leukemia virus in cattle under 3 years old with enzootic bovine leukosis. PLOS ONE, 18(1), Article e0279756. https://doi.org/10.1371/journal.pone.0279756
16. Szynal, M., Cleuter, Y., Beskorwayne, T., Bagnis, C., Van Lint, C., Kerkhofs, P. et al. (2003). Disruption of B-cell homeostatic control mediated by the BLV-Tax oncoprotein: Association with the upregulation of Bcl-2 and signaling through NF-κB. Oncogene, 22, 4531–4542. https://doi.org/10.1038/sj.onc.1206546
17. Inoue, E., Matsumura, K., Soma, N., Hirasawa, S., Wakimoto, M., Arakaki, Y. et al. (2013). L233P mutation of the Tax protein strongly correlated with leukemogenicity of bovine leukemia virus. Veterinary Microbiology, 167(3–4), 364–371. https://doi.org/10.1016/j.vetmic.2013.09.026
18. Wang, H., Norris, K. M., Mansky, L. M. (2003). Involvement of the matrix and nucleocapsid domains of the bovine leukemia virus Gag polyprotein precursor in viral RNA packaging. Journal of Virology, 77(17), 9431–3438. https://doi.org/10.1128/jvi.77.17.9431–9438.2003
19. Sperka, T., Miklóssy, G., Tie, Y., Bagossi, P., Zahuczky, G., Boross, P. et al. (2007). Bovine leukemia virus protease: Сomparison with human T-lymphotropic virus and human immunodeficiency virus proteases. Journal of General Virology, 88(7), 2052–2063. https://doi.org/10.1099/vir.0.82704–0
20. Sebastián-Martín, A., Barrioluengo, V., Menéndez-Arias, L. (2018). Transcriptional inaccuracy threshold attenuates differences in RNA-dependent DNA synthesis fidelity between retroviral reverse transcriptases. Scientific Reports, 8, Article 627. https://doi.org/10.1038/s41598–017–18974–8
21. Mansky, L. M., Temin, H. M. (1994). Lower mutation rate of bovine leukemia virus relative to that of spleen necrosis virus. Journal of Virology, 68(1), 494–499. https://doi.org/10.1128/jvi.68.1.494–499.1994
22. Wattel, E., Vartanian, J. P., Pannetier, C., Wain-Hobson, S. (1995). Clonal expansion of human T-cell leukemia virus type I-infected cells in asymptomatic and symptomatic carriers without malignancy. Journal of Virology, 69(5), 2863–2868. https://doi.org/10.1128/jvi.69.5.2863–2868.1995
23. Perach, M., Hizi, A. (1999). Catalytic features of the recombinant reverse transcriptase of bovine leukemia virus expressed in bacteria. Virology, 259(1), 176– 189. https://doi.org/10.1006/viro.1999.9761
24. Lamb, D., Schüttelkopf, A. W., van Aalten, D. M., Brighty, D. W. (2011). Chargesurrounded pockets and electrostatic interactions with small ions modulate the activity of retroviral fusion proteins. PLOS Pathogens, 7(2), Article e1001268. https://doi.org/10.1371/journal.ppat.1001268
25. Wallin, M., Ekström, M., Garoff, H. (2004). Isomerization of the intersubunit disulphide-bond in Env controls retrovirus fusion. The EMBO Journal, 23(1), 54–65. https://doi.org/10.1038/sj.emboj.7600012
26. Bruck, C., Mathot, S., Portetelle, D., Berte, C., Franssen, J. D., Herion, P. et al. (1982). Monoclonal antibodies define eight independent antigenic regions on the bovine leukemia virus (BLV) envelope glycoprotein gp51. Virology, 122(2), 342–352. https://doi.org/10.1016/0042–6822(82)90234–3
27. Zarkik, S., Defrise-Quertain, F., Portetelle, D., Burny, A., Ruysschaert. J. M. (1997). Fusion of bovine leukemia virus with target cells monitored by R18 fluorescence and PCR assays. Journal of Virology, 71(1), 738–740. https://doi.org/10.1128/JVI.71.1.738–740.1997
28. Bai, L., Takeshima, S. N., Isogai, E., Kohara, J., Aida, Y. (2015). Novel CD8(+) cytotoxic T cell epitopes in bovine leukemia virus with cattle. Vaccine, 33(51), 7194–7202. https://doi.org/10.1016/j.vaccine.2015.10.128
29. De Brogniez, A., Mast, J., Willems, L. (2016). Determinants of the Bovine Leukemia Virus Envelope Glycoproteins Involved in Infectivity, Replication and Pathogenesis. Viruses, 8(4), Article 88. https://doi.org/10.3390/v8040088
30. Barez, P. Y., de Brogniez, A., Carpentier, A., Gazon, H., Gillet, N., Gutiérrez, G. et al. (2015). Recent advances in BLV research. Viruses, 7(11), 6080–6088. https://doi.org/10.3390/v7112929
31. Durkin, K., Rosewick, N., Artesi, M., Hahaut, V., Griebel, P., Arsic, N. et al. (2016). Characterization of novel Bovine Leukemia Virus (BLV) antisense transcripts by deep sequencing reveals constitutive expression in tumors and transcriptional interaction with viral microRNAs. Retrovirology, 13(1), Article 33. https://doi.org/10.1186/s12977–016–0267–8
32. Pluta, A., Jaworski, J. P., Douville, R. N. (2020). Regulation of Expression and Latency in BLV and HTLV. Viruses, 12(10), Article 1079. https://doi.org/10.3390/v12101079
33. Arainga, M., Takeda, E., Aida, Y. (2012). Identification of bovine leukemia virus tax function associated with host cell transcription, signaling, stress response and immune response pathway by microarray-based gene expression analysis. BMC Genomics, 13, Article 121. https://doi.org/10.1186/1471–2164–13–121
34. Tajima, S., Aida, Y. (2005). Induction of expression of bovine leukemia virus (BLV) in blood taken from BLV-infected cows without removal of plasma. Microbes and Infection, 7(11–12), 1211–1216. https://doi.org/10.1016/j.micinf.2005.04.010
35. Inabe, K., Ikuta, K., Aida, Y. (1998). Transmission and propagation in cell culture of virus produced by cells transfected with an infectious molecular clone of bovine leukemia virus. Virology, 245(1), 53–64. https://doi.org/10.1006/viro.1998.9140
36. Derse, D. (1988). Trans-acting regulation of bovine leukemia virus mRNA processing. Journal of Virology, 62(4), 1115–1119. https://doi.org/10.1128/JVI.62.4.1115–1119.1988
37. Edwards, D., Fenizia, C., Gold, H., de Castro-Amarante, M. F., Buchmann, C., Pise-Masison, C.A. et al. (2011). Orf-I and orf-II-encoded proteins in HTLV-1 infection and persistence. Viruses, 3(6), 861–885. https://doi.org/10.3390/v3060861
38. Montero Machuca, N., Tórtora Pérez, J. L., González Méndez, A. S., García-Camacho, A. L., Marín Flamand, E., Ramírez Álvarez, H. (2022). Genetic analysis of the pX region of bovine leukemia virus genotype 1 in Holstein Friesian cattle with different stages of infection. Archives of Virology, 167, 45–56. https://doi.org/10.1007/s00705–021–05252–2
39. Lefèbvre, L., Ciminale, V., Vanderplasschen, A., D’Agostino, D., Burny, A., Willems, L. et al. (2002). Subcellular localization of the bovine leukemia virus R3 and G4 accessory proteins. Journal of Virology, 76(15), 7843–7854. https://doi.org/10.1128/jvi.76.15.7843–7854.2002
40. Murakami, H., Uchiyama, J., Nikaido, S., Sato, R., Sakaguchi, M., Tsukamoto, K. (2016). Inefficient viral replication of bovine leukemia virus induced by spontaneous deletion mutation in the G4 gene. Journal of General Virology, 97(10), 2753–2762. https://doi.org/10.1099/jgv.0.000583
41. Zyrianova, I. M., Koval’chuk, S. N. (2018). Bovine leukemia virus pre-miRNA genes’ polymorphism. RNA Biology, 15(12), 1440–1447. https://doi.org/10.1080/15476286.2018.1555406
42. Jimba, M., Takeshima, Sn., Murakami, H., Kohara, J., Kobayashi, N., Matsuhashi, T. et al. (2012). BLV–CoCoMo-qPCR: a useful tool for evaluating bovine leukemia virus infection status. BMC Veterinary Research, 8, Article 167. https://doi.org/10.1186/1746–6148–8–167
43. Borjigin, L., Yoneyama, S., Saito, S., Polat, M., Inokuma, M., Shinozaki, Y. et al. (2021). A novel real time PCR assay for bovine leukemia virus detection using mixed probes and degenerate primers targeting novel BLV strains. Journal of Virological Methods, 297, Article 114264. https://doi.org/10.1016/j.jviromet.2021.114264
44. Corredor-Figueroa, A. P., Salas, S., Olaya-Galán, N. N., Quintero, J. S., Fajardo, Á., Soñora, M. et al. (2020). Prevalence and molecular epidemiology of bovine leukemia virus in Colombian cattle. Infection, Genetics and Evolution, 80, Article 104171. https://doi.org/10.1016/j.meegid.2020.104171
45. Dimitrov, P., Simeonov, K., Todorova, K., Ivanova, Z., Toshkova, R., Shikova, E. et al. (2012). Pathological features of experimental bovine leukaemia viral (BLV) infection in rats and rabbits. Bulletin of the Veterinary Institute in Pulawy, 56, 115–120. https://doi.org/10.2478/v10213–012–0021–5
46. Fechner, H., Kurg, A., Geue, L., Blankenstein, P., Mewes, G., Ebner. D. et al. (1996). Evaluation of Polymerase Chain Reaction (PCR) application in diagnosis of Bovine Leukaemia Virus (BLV) infection in naturally infected cattle. Zoonoses and Public Health, 43(1–10), 621–630. https://doi.org/10.1111/j.1439–0450.1996.tb00361.x
47. Choi, K. Y., Monke, D., Stott, J. L. (2002). Absence of bovine leukosis virus in semen of seropositive bulls. Journal of Veterinary Diagnostic Investigation, 14(5), 403–406. https://doi.org/10.1177/104063870201400507
48. Alvarez, I., Porta, N. G., Trono, K. (2019). Detection of Bovine Leukemia Virus RNA in blood samples of naturally infected dairy cattle. Veterinary Sciences, 6(3), Article 66. https://doi.org/10.3390/vetsci6030066
49. Klintevall, K., Ballagi-Pordány, A., Näslund, K., Belák, S. (1994). Bovine leukaemia virus: rapid detection of proviral DNA by nested PCR in blood and organs of experimentally infected calves. Veterinary Microbiology, 42(2–3), 191–204. https://doi.org/10.1016/0378–1135(94)90018–3
50. Uera, J. A., Lazaro, J. V., Mingala, C. (2012). Detection of Enzootic Bovine Leukosis in cattle using nested Polymerase Chain Reaction assay. Thai Journal of Veterinary Medicine, 42(3), 319–324. https://he01.tci-thaijo.org/index.php/tjvm/article/view/10988
51. Polat, M., Ohno, A., Takeshima, Sn., Kim, J., Kikuya, M., Matsumoto, Y. et al. (2015). Detection and molecular characterization of bovine leukemia virus in Philippine cattle. Archives of Virology, 160, 285–296. https://doi.org/10.1007/s00705–014–2280–3
52. D’Angelino, R. H. R., Pituco, E. M., Villalobos, E. M. C., Harakava, R., Gregori, F., Del Fava, C. (2013). Detection of Bovine Leukemia Virus in brains of cattle with a neurological syndrome: Pathological and molecular studies. Bio Med Research International, 2013, Article 425646. https://doi.org/10.1155/2013/425646
53. Villalobos-Cortés, A., Franco, S., González, R. G., Jaen, M. W. (2017). Nested polymerase chain reaction (nPCR) based diagnosis of bovine leukemia virus in Panama. African Journal of Biotechnology, 16, 528–535. https://doi.org/10.5897/AJB2016.15849
54. Nishimori, A., Konnai, S., Ikebuchi, R., Okagawa, T., Nakahara, A., Murata, S. et al. (2016). Direct polymerase chain reaction from blood and tissue samples for rapid diagnosis of bovine leukemia virus infection. The Journal of Veterinary Medical Science, 78(5), 791–796. https://doi.org/10.1292/jvms.15–0577
55. Takeshima, Sn., Watanuki, S., Ishizaki, H., Matoba, K., Aida, Y. (2016). Development of a direct blood-based PCR system to detect BLV provirus using CoCoMo primers. Archives of Virology, 161, 1539–1546. https://doi.org/10.1007/s00705–016–2806-y
56. El Daous, H., Mitoma, S., Elhanafy, E., Thi Nguyen, H., Thi Mai, N., Hara, A. et al. (2020). Establishment of a novel diagnostic test for Bovine Leukaemia virus infection using direct filter PCR. Transboundary and Emerging Diseases, 67(4), 1671–1676. https://doi.org/10.1111/tbed.13506
57. Wu, X., Notsu, K., Matsuura, Y., Mitoma, S., El Daous, H., Norimine, J. et al. (2023). Development of droplet digital PCR for quantification of bovine leukemia virus proviral load using unpurified genomic DNA. Journal of Virological Methods, 315, Article 114706. https://doi.org/10.1016/j.jviromet.2023.114706
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Fomenko O.Yu. Structural characteristics of the bovine leukemia virus genome: A mini review. Food systems. 2023;6(3):283-287. (In Russ.) https://doi.org/10.21323/2618-9771-2023-6-3-283-287
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