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Absence of bovine leukemia virus proviral DNA in Japanese human blood cell lines and human cancer cell lines

Abstract

Bovine leukemia virus (BLV) infects cattle worldwide and causes B-cell lymphoma in cattle. BLV has been identified in human breast and lung cancer and in blood, but the association of BLV and human cancer is controversial. In this study, we investigated the existence of BLV in 145 Japanese human blood cell lines and 54 human cancer cell lines, using a new highly sensitive PCR assay that can amplify even one copy of BLV using LTR primers different from those in previous studies on BLV provirus in breast cancer. All samples were found negative for BLV provirus, suggesting that BLV is unlikely to infect humans.

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References

  1. Altaner C, Altanerová V, Bán J, Niwa O, Yokoro K (1989) Human cells of neural origin are permissive for bovine leukemia virus. Neoplasma 36:691–695

    CAS  PubMed  Google Scholar 

  2. Altanerova V, Ban J, Kettmann R, Altaner C (1990) Induction of leukemia in chicken by bovine leukemia virus due to insertional mutagenesis. Arch Geschwulstforsch 60:89–96

    CAS  PubMed  Google Scholar 

  3. Aida Y, Miyasaka M, Okada K, Onuma M, Kogure S, Suzuki M, Minoprio P, Levy D, Ikawa Y (1989) Further phenotypic characterization of target cells for bovine leukemia virus experimental infection in sheep. Am J Vet Res 50:1946–1951

    CAS  PubMed  Google Scholar 

  4. Aida Y, Murakami H, Takahashi M, Takeshima SN (2013) Mechanisms of pathogenesis induced by bovine leukemia virus as a model for human T-cell leukemia virus. Front Microbiol 4:328. https://doi.org/10.3389/fmicb.2013.00328

    Article  PubMed  PubMed Central  Google Scholar 

  5. Buehring GC, Philpott SM, Choi KY (2003) Humans have antibodies reactive with bovine leukemia virus. AIDS Res Hum Retroviruses 19:1105–1113. https://doi.org/10.1089/088922203771881202

    CAS  Article  PubMed  Google Scholar 

  6. Buehring GC, Shen HM, Jensen HM, Choi KY, Sun D, Nuovo G (2014) Bovine leukemia virus DNA in human breast tissue. Emerg Infect Dis 20:772–782. https://doi.org/10.3201/eid2005.131298

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  7. Bai L, Otsuki H, Sato H, Kohara J, Isogai E, Takeshima SN, Aida Y (2015) Identification and characterization of common B cell epitope in bovine leukemia virus via high-throughput peptide screening system in infected cattle. Retrovirology 12:106. https://doi.org/10.1186/s12977-015-0233-x

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  8. Buehring GC, Shen HM, Jensen HM, Jin DL, Hudes M, Block G (2015) Exposure to bovine leukemia virus is associated with breast cancer: a case–control study. PLoS One. https://doi.org/10.1371/journal.pone.0134304

    Article  PubMed  PubMed Central  Google Scholar 

  9. Buehring GC, Shen H, Schwartz DA, Lawson JS (2017) Bovine leukemia virus linked to breast cancer in Australian women and identified before breast cancer development. PLoS One 12:e0179367. https://doi.org/10.1371/journal.pone.0179367

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  10. Baltzell KA, Shen HM, Krishnamurthy S, Sison JD, Nuovo GJ, Buehring GC (2018) Bovine leukemia virus linked to breast cancer but not coinfection with human papillomavirus: case–control study of women in Texas. Cancer 124:1342–1349. https://doi.org/10.1002/cncr.31169

    Article  PubMed  Google Scholar 

  11. Buehring GC, DeLaney A, Shen H, Chu DL, Razavian N, Schwartz DA, Demkovich ZR, Bates MN (2019) Bovine leukemia virus discovered in human blood. BMC Infect Dis 19:297. https://doi.org/10.1186/s12879-019-3891-9

    Article  PubMed  PubMed Central  Google Scholar 

  12. Giovanna M, Carlos UJ, Mariá UA, Gutierrez MF (2013) Bovine leukemia virus gene segment detected in human breast tissue. Open J Med Microbiol 3:84–90. https://doi.org/10.4236/ojmm.2013.31013

    CAS  Article  Google Scholar 

  13. Gillet NA, Willems L (2016) Whole genome sequencing of 51 breast cancers reveals that tumors are devoid of bovine leukemia virus DNA. Retrovirology 13:75. https://doi.org/10.1186/s12977-016-0308-3

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  14. Godos J, Tieri M, Ghelfi F, Titta L, Marventano S, Lafranconi A, Gambera A, Alonzo E, Sciacca S, Buscemi S, Ray S, Del Rio D, Galvano F, Grosso G (2019) Dairy foods and health: an umbrella review of observational studies. Int J Food Sci Nutr 14:1–14. https://doi.org/10.1080/09637486

    Article  Google Scholar 

  15. Hopkins SG, DiGiacomo RF (1997) Natural transmission of bovine leukemia virus in dairy and beef cattle. Vet Clin North Am Food Anim Pract 13:107–128

    CAS  Article  PubMed  Google Scholar 

  16. 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 245:53–64

    CAS  Article  PubMed  Google Scholar 

  17. Johnson ES (2011) Cancer mortality in workers employed in cattle, pigs, and sheep slaughtering and processing plants. Environ Int 37:950–959. https://doi.org/10.1016/j.envint.2011.03.014

    CAS  Article  PubMed  Google Scholar 

  18. Johnson ES, Cardarelli K, Jadhav S, Chedjieu IP, Faramawi M, Fischbach L, Ndetan H, Wells TL, Patel KV, Katyal A (2015) Cancer mortality in the meat and delicatessen departments of supermarkets (1950–2006). Environ Int 77:70–75. https://doi.org/10.1016/j.envint.2015.01.009

    CAS  Article  PubMed  Google Scholar 

  19. Kettmann R, Deschamps J, Cleuter Y, Couez D, Burny A, Marbaix G (1982) Leukemogenesis by bovine leukemia virus: proviral DNA integration and lack of RNA expression of viral long terminal repeat and 3’ proximate cellular sequences. Proc Natl Acad Sci USA 79:2465–2469. https://doi.org/10.1073/pnas.79.8.2465

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  20. Kettmann R, Mammerickx M, Portetelle D, Grégoire D, Burny A (1984) Experimental infection of sheep and goat with bovine leukemia virus: localization of proviral information on the target cells. Leuk Res 8:937–944

    CAS  Article  PubMed  Google Scholar 

  21. Khalilian M, Hosseini SM, Madadgar O (2019) Bovine leukemia virus detected in the breast tissue and blood of Iranian women. Microb Pathog 135:103566. https://doi.org/10.1016/j.micpath.2019.103566

    Article  PubMed  Google Scholar 

  22. Lee J, Kim Y, Kang CS, Cho DH, Shin DH, Yum YN, Oh JH, Kim SH, Hwang MS, Lim CJ, Yang KH, Han K (2005) Investigation of the bovine leukemia virus proviral DNA in human leukemias and lung cancers in Korea. J Korean Med Sci 20:603–606. https://doi.org/10.3346/jkms.2005.20.4.603

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  23. Lawson JS, Glenn WK (2017) Multiple oncogenic viruses are present in human breast tissues before development of virus associated breast cancer. Infect Agent Cancer 12:55. https://doi.org/10.1186/s13027-017-0165-2

    Article  PubMed  PubMed Central  Google Scholar 

  24. Lawson JS, Salmons B, Glenn WK (2018) Oncogenic viruses and breast cancer: mouse mammary tumor virus (MMTV), bovine leukemia virus (BLV), human papilloma virus (HPV), and Epstein–Barr virus (EBV). Front Oncol 8:1. https://doi.org/10.3389/fonc.2018.00001

    Article  PubMed  PubMed Central  Google Scholar 

  25. Mammerickx M, Portetelle D, de Clercq K, Burny A (1987) Experimental transmission of enzootic bovine leukosis to cattle, sheep and goats: infectious doses of blood and incubation period of the disease. Leuk Res 11:353–358

    CAS  Article  PubMed  Google Scholar 

  26. Meas S, Seto J, Sugimoto C, Bakhsh M, Riaz M, Sato T, Naeem K, Ohashi K, Onuma M (2000) Infection of bovine immunodeficiency virus and bovine leukemia virus in water buffalo and cattle populations in Pakistan. J Vet Med Sci 62:329–331. https://doi.org/10.1292/jvms.62.329

    CAS  Article  PubMed  Google Scholar 

  27. Molnár E, Molnár L, Guedes VT, de Lima ES (2000) Naturally occurring bovine leukosis virus in water buffalo (Bubalus bubalis) in Brazil. Vet Rec 146:705–706. https://doi.org/10.1136/vr.146.24.705

    Article  PubMed  Google Scholar 

  28. McLean D, Pearce N (2004) Cancer among meat industry workers. Scand J Work Environ Health 30:425–437

    Article  PubMed  Google Scholar 

  29. Ma JG, Zheng WB, Zhou DH, Qin SY, Yin MY, Zhu XQ, Hu GX (2016) First report of bovine leukemia virus infection in Yaks (Bos mutus) in China. Biomed Res Int 2016:9170167. https://doi.org/10.1155/2016/9170167

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  30. Nilsson LM, Winkvist A, Esberg A, Jansson JH, Wennberg P, Van Guelpen B, Johansson I (2019) Dairy products and cancer risk in a Northern Sweden population. Nutr Cancer 12:1–12. https://doi.org/10.1080/01635581

    Article  Google Scholar 

  31. Olaya-Galán NN, Corredor-Figueroa AP, Guzmán-Garzón TC, Ríos-Hernandez KS, Salas-Cárdenas SP, Patarroyo MA, Gutierrez MF (2017) Bovine leukaemia virus DNA in fresh milk and raw beef for human consumption. Epidemiol Infect 145:3125–31230. https://doi.org/10.1017/S0950268817002229

    CAS  Article  PubMed  Google Scholar 

  32. Robinson LA, Jaing CJ, Pierce Campbell C, Magliocco A, Xiong Y, Magliocco G, Thissen JB, Antonia S (2016) Molecular evidence of viral DNA in non-small cell lung cancer and non-neoplastic lung. Br J Cancer 115:497–504. https://doi.org/10.1038/bjc.2016.213

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  33. Sláviková K, Zajac V, Reinerová M, Kettmann R, Burny A (1986) Bovine leukemia provirus in the DNA of different infected host cells. Neoplasma 33:671–678

    PubMed  Google Scholar 

  34. Sláviková K, Kettmann R, Reinerová M, Zajac V, Portetelle D, Burny A (1987) Provirus integration of bovine leukemia virus into DNA of infected human myeloma cells. Neoplasma 34:653–657

    PubMed  Google Scholar 

  35. Schwartz I, Bensaid A, Polack B, Perrin B, Berthelemy M, Levy D (1994) In vivo leukocyte tropism of bovine leukemia virus in sheep and cattle. J Virol 68:4589–4596

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  36. Schwingel D, Andreolla AP, Erpen LMS, Frandoloso R, Kreutz LC (2019) Bovine leukemia virus DNA associated with breast cancer in women from South Brazil. Sci Rep 9:2949. https://doi.org/10.1038/s41598-019-39834-7

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  37. Tajima S, Ikawa Y, Aida Y (1998) Complete bovine leukemia virus (BLV) provirus is conserved in BLV-infected cattle throughout the course of B-cell lymphosarcoma development. J Virol 72:7569–7576

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  38. Tajima S, Takahashi M, Takeshima SN, Konnai S, Yin SA, Watarai S, Tanaka Y, Onuma M, Okada K, Aida Y (2003) A mutant form of the tax protein of bovine leukemia virus (BLV), with enhanced transactivation activity, increases expression and propagation of BLV in vitro but not in vivo. J Virol 77:1894–1903. https://doi.org/10.1128/jvi77.3.1894-1903.2003

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  39. Wyatt CR, Wingett D, White JS, Buck CD, Knowles D, Reeves R, Magnuson NS (1989) Persistent infection of rabbits with bovine leukemia virus associated with development of immune dysfunction. J Virol 63:4498–4506

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  40. Yuan Y, Kitamura-Muramatsu Y, Saito S, Ishizaki H, Nakano M, Haga S, Matoba K, Ohno A, Murakami H, Takeshima SN, Aida Y (2015) Detection of the BLV provirus from nasal secretion and saliva samples using BLV-CoCoMo-qPCR-2: comparison with blood samples from the same cattle. Virus Res 210:248–254. https://doi.org/10.1016/j.virusres.2015.08.013

    CAS  Article  PubMed  Google Scholar 

  41. Zhang R, Jiang J, Sun W, Zhang J, Huang K, Gu X, Yang Y, Xu X, Shi Y, Wang C (2016) Lack of association between bovine leukemia virus and breast cancer in Chinese patients. Breast Cancer Res 18:101. https://doi.org/10.1186/s13058-016-0763-8

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank Yoshinori Tanaka and Junko Nakamura for providing technical support, kind help, and suggestions. We also thank Tatsuro Saito for kindly providing the DNA from human cancer cell lines. We would like to thank Editage (http://www.editage.com) for English language editing. This work was supported by a Grant-in-Aid for Scientific Research (A) from the Japan Society for the Promotion of Science (JSPS) (Grant no. 16H02590) and by the Japan Society for the JSPS Postdoctoral Fellowship (Grant no. 18F18100).

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Correspondence to Yoko Aida.

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Human DNA samples derived from unrelated healthy volunteers were acquired from the Japanese Collection of Research Bioresources (JCRB) Cell Bank. The study protocol was approved by the Ethics Committee for the Protection of Human Subjects at RIKEN GENESIS CO., LTD.

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Saito, S., Kitamura-Muramatsu, Y., Komine, F. et al. Absence of bovine leukemia virus proviral DNA in Japanese human blood cell lines and human cancer cell lines. Arch Virol 165, 207–214 (2020). https://doi.org/10.1007/s00705-019-04474-9

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  • DOI: https://doi.org/10.1007/s00705-019-04474-9