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Chimeric provirus of bovine leukemia virus/SMAD family member 3 in cattle with enzootic bovine leukosis

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Abstract

Bovine leukemia virus (BLV) is a member of the family Retroviridae that causes enzootic bovine leukemia (EBL). However, the association between BLV infection and EBL development remains unclear. In this study, we identified a BLV/SMAD3 chimeric provirus within CC2D2A intron 30 in monoclonal expanded malignant cells from a cow with EBL. The chimeric provirus harbored a spliced SMAD3 sequence composed of exons 3–9, encoding the short isoform protein, and the BLV-SMAD3 chimeric transcript was detectable in cattle with EBL. This is the first report of a BLV chimeric provirus that might be involved in EBL tumorigenesis.

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Fig. 1
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Data availability

The complete sequence of the BLV/SMAD3 chimeric provirus in EBL091 has been deposited in the GenBank database under the accession number LC728442.

References

  1. Rosewick N, Durkin K, Artesi M, Marçais A, Hahaut V, Griebel P et al (2017) Cis-perturbation of cancer drivers by the HTLV-1/BLV proviruses is an early determinant of leukemogenesis. Nat Commun 8:15264

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  2. Polat M, Takeshima SN, Aida Y (2017) Epidemiology and genetic diversity of bovine leukemia virus. Virol J 14(1):209

    Article  PubMed  PubMed Central  Google Scholar 

  3. Khatami A, Pormohammad A, Farzi R, Saadati H, Mehrabi M, Kiani SJ et al (2020) Bovine leukemia virus (BLV) and risk of breast cancer: a systematic review and meta-analysis of case-control studies. Infect Agent Cancer 15:48

    Article  PubMed  PubMed Central  Google Scholar 

  4. Gillet NA, Willems L (2016) Whole genome sequencing of 51 breast cancers reveals that tumors are devoid of bovine leukemia virus DNA. Retrovirology 13(1):75

    Article  PubMed  PubMed Central  Google Scholar 

  5. Wada Y, Sato T, Hasegawa H, Matsudaira T, Nao N, Coler-Reilly ALG et al (2022) RAISING is a high-performance method for identifying random transgene integration sites. Commun Biol 5(1):535

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Okagawa T, Shimakura H, Konnai S, Saito M, Matsudaira T, Nao N et al (2022) Diagnosis and early prediction of lymphoma using high-throughput clonality analysis of bovine leukemia virus-infected cells. Microbiol Spectr 10(6):e0259522

    Article  PubMed  Google Scholar 

  7. Lai MM (1992) RNA recombination in animal and plant viruses. Microbiol Rev 56(1):61–79

    Article  MathSciNet  CAS  PubMed  PubMed Central  Google Scholar 

  8. Mansky LM (1998) Retrovirus mutation rates and their role in genetic variation. The J Gen Virol 79(Pt 6):1337–1345

    Article  CAS  PubMed  Google Scholar 

  9. Jetzt AE, Yu H, Klarmann GJ, Ron Y, Preston BD, Dougherty JP (2000) High rate of recombination throughout the human immunodeficiency virus type 1 genome. J Virol 74(3):1234–1240

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Jung A, Maier R, Vartanian JP, Bocharov G, Jung V, Fischer U et al (2002) Recombination: Multiply infected spleen cells in HIV patients. Nature 418(6894):144

    Article  ADS  CAS  PubMed  Google Scholar 

  11. Bushman F, Lewinski M, Ciuffi A, Barr S, Leipzig J, Hannenhalli S et al (2005) Genome-wide analysis of retroviral DNA integration. Nat Rev Microbiol 3(11):848–858

    Article  CAS  PubMed  Google Scholar 

  12. Kawamura M, Umehara D, Odahara Y, Miyake A, Ngo MH, Ohsato Y et al (2017) AKT capture by feline leukemia virus. Arch Virol 162(4):1031–1036

    Article  CAS  PubMed  Google Scholar 

  13. Roberts AB, Flanders KC, Heine UI, Jakowlew S, Kondaiah P, Kim SJ et al (1990) Transforming growth factor-beta: multifunctional regulator of differentiation and development. Philos Trans R Soc Lond B Biol Sci 327(1239):145–154

    Article  ADS  CAS  PubMed  Google Scholar 

  14. Kim SY, Zhu J, Woodruff TK (2011) A truncated, activin-induced Smad3 isoform acts as a transcriptional repressor of FSHbeta expression in mouse pituitary. Mol Cell Endocrinol 342(1–2):64–72

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Chen CR, Kang Y, Siegel PM, Massague J (2002) E2F4/5 and p107 as Smad cofactors linking the TGFbeta receptor to c-myc repression. Cell 110(1):19–32

    Article  CAS  PubMed  Google Scholar 

  16. Korac P, Dotlic S, Matulic M, Zajc Petranovic M, Dominis M (2017) Role of MYC in B Cell Lymphomagenesis. Genes (Basel). ;8(4)

  17. Li X, Wang W, Xi Y, Gao M, Tran M, Aziz KE et al (2016) FOXR2 Interacts with MYC to Promote Its Transcriptional Activities and Tumorigenesis. Cell Rep 16(2):487–497

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

We thank Susan Furness, PhD, from Edanz (https://jp.edanz.com/ac) for editing a draft of this manuscript.

Funding

This study was supported by the Grants-in-Aid for Scientific Research (project numbers 17H03594 to MS, 19KK0172, 22H02503, and 22K19232 to SK, and 19K15993 and 22K15005 to TO); grants from the Ito Memorial Foundation (to SK); the Science and Technology Research Promotion Program for Agriculture, Forestry, Fisheries, and Food Industry, Japan (number 26058B; to SK); the NARO Bio-oriented Technology Research Advancement Institution (the special scheme project on developing regional strategy; grant 16817557 to SK); Clinical Research Promotion Fund by the Hokkaido University Veterinary Teaching Hospital (to SK); World-leading Innovative and Smart Education Program 1801 from the Ministry of Education, Culture, Sports, Science and Technology (to NN); Ministry of Health, Labour and Welfare (MHLW) under grant 23HA2010 (to NN); the Japan Agency for Medical Research and Development (AMED) SCARDA Hokkaido University Institute for Vaccine Research and Development (HU-IVReD) (to NN), and the Japan Program for Infectious Diseases Research and Infrastructure (JP22wm0125008) from AMED (to NN). The funders had no role in the study design, data collection, interpretation, or decision to submit the paper for publication.

Author information

Author notes

  1. Naganori Nao, Tomohiro Okagawa and Naomi Nojiri contributed equally to this work.

Authors and Affiliations

  1. Division of International Research Promotion, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Japan

    Naganori Nao

  2. One Health Research Center, Hokkaido University, Sapporo, Japan

    Naganori Nao

  3. Institute for Vaccine Research and Development (IVReD), Hokkaido University, Sapporo, Japan

    Naganori Nao

  4. Department of Advanced Pharmaceutics, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan

    Tomohiro Okagawa, Satoru Konnai, Naoya Maekawa, Shiro Murata & Kazuhiko Ohashi

  5. Center for Emergency Preparedness and Response, National Institute of Infectious Diseases, Tokyo, Japan

    Naomi Nojiri, Hazuka Yoshida-Furihata & Masumichi Saito

  6. Department of Disease Control, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan

    Satoru Konnai, Honami Shimakura, Misono Tominaga, Shiro Murata & Kazuhiko Ohashi

  7. Biotechnological Research Support Division, FASMAC Co., Ltd, Atsugi, Japan

    Eri Nishiyama & Takahiro Matsudaira

  8. Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan

    Masamichi Muramatsu & Masumichi Saito

Authors
  1. Naganori Nao
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  2. Tomohiro Okagawa
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  3. Naomi Nojiri
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  4. Satoru Konnai
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  9. Takahiro Matsudaira
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  10. Naoya Maekawa
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  11. Shiro Murata
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  14. Masumichi Saito
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Contributions

T.O., N.No, H.S., T.M., S.Y., M.T., H.Y.F., E.N., N.M., S.M., and M.S performed the research; N.Na performed the data analysis; N.Na., T.S., T.O., S.K., M.M., K.O., and M.S. wrote the manuscript; and K.S., T.M., M.M., K.O., and M.S. supervised the study.

Corresponding authors

Correspondence to Satoru Konnai or Masumichi Saito.

Ethics declarations

Ethics approval

The animal experiments were approved by the Ethics Committee of the Faculty of Veterinary Medicine, Hokkaido University (approval #17–0024). Verbal informed consent was obtained from the owners for the use of their animals in this study.

Competing interest

MS and TM have a patent pending for the materials and techniques described in this paper (application number PCT/JP2020/30907). The other authors declare no competing interests.

Additional information

Communicated by YiMing Shao

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Nao, N., Okagawa, T., Nojiri, N. et al. Chimeric provirus of bovine leukemia virus/SMAD family member 3 in cattle with enzootic bovine leukosis. Arch Virol 169, 47 (2024). https://doi.org/10.1007/s00705-024-05970-3

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