Skip to main content

Advertisement

SpringerLink
Log in

Interaction between Bovine leukemia virus (BLV) infection and age on telomerase misregulation

  • Original Article
  • Published:
Veterinary Research Communications Aims and scope Submit manuscript

Abstract

Bovine leukemia virus (BLV) is the causative agent of enzootic bovine leukosis (EBL). BLV can interact with telomerase and inhibits telomere shortening, contributing in leukemogenesis and tumour induction. The role of telomerase in BLV-induced lymphosarcoma and aging has been extensively studied. To date, the interaction of both BLV and aging on telomerase mis-regulation have, however, not been investigated. In the present study, telomerase activity in BLV positive and negative cows was compared over a wide range of ages (11–85 months). Lymphocyte counts were also measured in both BLV positive and negative groups. Telomerase activity was detected in all BLV infected animals with persistent lymphocytosis (PL), especially in older individuals. This study revealed that the cells undergo the natural telomerase shortening even in the presence of an existing viral infection. We also show that viral infection, especially during the PL phase of the disease, increases telomerase activity. A statistically significant interaction between age and viral infection was observed for telomere shortening during BLV infection. Older animals with BLV infection, especially those with persistent lymphocytosis or visible tumors, exhibited a sharp increase in telomerase activity. This study demonstrates that there is a significant interaction between BLV infection and telomerase up-regulation and lymphocytosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Ababneh MM, Al-Rukibat RK, Hananeh WM et al (2012) Detection and molecular characterization of bovine leukemia viruses from Jordan. Arch Virol 157:2343–2348

    Article  CAS  PubMed  Google Scholar 

  • Aida Y, Murakami H, Takahashi M et al (2013) Mechanisms of pathogenesis induced by bovine leukemia virus as a model for human T-cell leukemia virus. Front Microbiol 4:328

    Article  PubMed Central  PubMed  Google Scholar 

  • Betts DH, Bordignon V, Hill JR et al (2001) Reprogramming of telomerase activity and rebuilding of telomere length in cloned cattle. Proc Natl Acad Sci 98:1077–1082

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Blackburn EH (1991) Structure and function of telomeres. Nature 350:569–573

    Article  CAS  PubMed  Google Scholar 

  • Blackburn EH (2005) Telomerase and Cancer: Kirk A. Landon–AACR prize for basic cancer research lecture. Mol Cancer Res: MCR 3:477–482

    Article  CAS  PubMed  Google Scholar 

  • Burny A, Cleuter Y, Kettmann R et al (1988) Bovine leukaemia: facts and hypotheses derived from the study of an infectious cancer. Vet Microbiol 17:197–218

    Article  CAS  PubMed  Google Scholar 

  • Camargos MF, Pereda A, Stancek D et al (2007) Molecular characterization of the env gene from Brazilian field isolates of Bovine leukemia virus. Virus Genes 34:343–350

    Article  CAS  PubMed  Google Scholar 

  • Chebel A, Bauwens S, Gerland LM et al (2009) Telomere uncapping during in vitro T-lymphocyte senescence. Aging Cell 8:52–64

    Article  CAS  PubMed  Google Scholar 

  • Counter CM, Botelho FM, Wang P et al (1994) Stabilization of short telomeres and telomerase activity accompany immortalization of Epstein-Barr virus-transformed human B lymphocytes. J Virol 68:3410–3414

    PubMed Central  CAS  PubMed  Google Scholar 

  • Debacq C, Asquith B, Kerkhofs P et al (2002) Increased cell proliferation, but not reduced cell death, induces lymphocytosis in bovine leukemia virus-infected sheep. Proc Natl Acad Sci 99:10048–10053

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Feist H, Zeidler R, Skrebsky T et al (1998) Induction of telomerase activity in stimulated human lymphocytes precedes expression of topoisomerase II alpha. Ann Hematol 76:111–115

    Article  CAS  PubMed  Google Scholar 

  • Florins A, Gillet N, Asquith B et al (2007) Cell dynamics and immune response to BLV infection: a unifying model. Front Biosci 12:1520–1531

    Article  CAS  PubMed  Google Scholar 

  • Gillet N, Florins A, Boxus M et al (2007) Mechanisms of leukemogenesis induced by bovine leukemia virus: prospects for novel anti-retroviral therapies in human. Retrovirology 4:18

    Article  PubMed Central  PubMed  Google Scholar 

  • Gutierrez G, Alvarez I, Merlini R et al (2014) Dynamics of perinatal bovine leukemia virus infection. BMC Vet Res 10:82

    Article  PubMed Central  PubMed  Google Scholar 

  • Hansson M, Zendehrokh N, Ohyashiki J et al (2008) Telomerase activity in effusions: a comparison between telomere repeat amplification protocol in situ and conventional telomere repeat amplification protocol assay. Arch Pathol Lab Med 132:1896–1902

    PubMed  Google Scholar 

  • Hemmatzadeh F (2007) Sequencing and phylogenetic analysis of gp51 gene of bovine leukaemia virus in Iranian isolates. Vet Res Commun 31:783–789

    Article  CAS  PubMed  Google Scholar 

  • Hemmatzadeh F, Reza Tofighi E, Keyvanfar H et al (2008) Investigation of env gene of bovine leukaemia virus in infected cows. Indian Vet J 85:924–926

    Google Scholar 

  • Hiyama K, Hirai Y, Kyoizumi S et al (1995) Activation of telomerase in human lymphocytes and hematopoietic progenitor cells. J Immunol (Baltim, Md: 1950) 155:3711–3715

    CAS  Google Scholar 

  • Ishiguro N, Furuoka H, Matsui T et al (1997) p53 mutation as a potential cellular factor for tumor development in enzootic bovine leukosis. Vet Immunol Immunopathol 55:351–358

    Article  CAS  PubMed  Google Scholar 

  • Jeon HY, Hyun SH, Lee GS et al (2005) The analysis of telomere length and telomerase activity in cloned pigs and cows. Mol Reprod Dev 71:315–320

    Article  CAS  PubMed  Google Scholar 

  • Kobayashi S, Hidano A, Tsutsui T et al (2014) Analysis of risk factors associated with bovine leukemia virus seropositivity within dairy and beef breeding farms in Japan: a nationwide survey. Res Vet Sci 96:47–53

    Article  CAS  PubMed  Google Scholar 

  • Letesson JJ, Mager A, Mammerickx M et al (1990) B cells from bovine leukemia virus- (BLV) infected sheep with hematological disorders express the CD5 T cell marker. Leukemia 4:377–379

    CAS  PubMed  Google Scholar 

  • Lu W, Zhang Y, Liu D et al (2013) Telomeres-structure, function, and regulation. Exp Cell Res 319:133–141

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Menzel O, Migliaccio M, Goldstein DR et al (2006) Mechanisms regulating the proliferative potential of human CD8+ T lymphocytes overexpressing telomerase. J Immunol (Baltim, Md : 1950) 177:3657–3668

    Article  CAS  Google Scholar 

  • Moore MS (1992) Does stem-cell exhaustion result from combining hematopoietic growth-factors with chemotherapy - if So, How Do We prevent it. Blood 80:3–7

    CAS  PubMed  Google Scholar 

  • Moratorio G, Fischer S, Bianchi S et al (2013) A detailed molecular analysis of complete bovine leukemia virus genomes isolated from B-cell lymphosarcomas. Vet Res 44:19

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Murakami K, Kobayashi S, Konishi M et al (2013) Nationwide survey of bovine leukemia virus infection among dairy and beef breeding cattle in Japan from 2009–2011. J Vet Med Sci 75:1123–1126

    Article  PubMed  Google Scholar 

  • Nasir L, Devlin P, Mckevitt T et al (2001) Telomere lengths and telomerase activity in dog tissues: a potential model system to study human telomere and telomerase biology. Neoplasia 3:351–359

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ott SL, Johnson R, Wells SJ (2003) Association between bovine-leukosis virus seroprevalence and herd-level productivity on US dairy farms. Prev Vet Med 61:249–262

    Article  CAS  PubMed  Google Scholar 

  • Rosewick N, Momont M, Durkin K et al (2013) Deep sequencing reveals abundant noncanonical retroviral microRNAs in B-cell leukemia/lymphoma. Proc Natl Acad Sci U S A 110:2306–2311

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Sambrook J (2001) Molecular cloning: a laboratory manual / Joseph Sambrook David W. Russell. Cold Spring Harbor Laboratory, Cold Spring Harbor

    Google Scholar 

  • Schoepf KC, Kapaga AM, Msami HM et al (1997) Serological evidence of the occurrence of enzootic bovine leukosis (EBL) virus infection in cattle in Tanzania. Trop Anim Health Prod 29:15–19

    Article  CAS  PubMed  Google Scholar 

  • Schwartz I, Levy D (1994) Pathobiology of bovine leukemia-virus. Vet Res 25:521–536

    CAS  PubMed  Google Scholar 

  • Shay JW, Bacchetti S (1997) A survey of telomerase activity in human cancer. Eur J Cancer (Oxf, Engl: 1990) 33:787–791

    Article  CAS  Google Scholar 

  • Shay JW, Wright WE (2007) Hallmarks of telomeres in ageing research. J Pathol 211:114–123

    Article  CAS  PubMed  Google Scholar 

  • Stone DM, Norton LK, Magnuson NS et al (1996) Elevated pim-1 and c-myc proto-oncogene induction in B lymphocytes from BLV-infected cows with persistent B lymphocytosis. Leukemia 10:1629–1638

    CAS  PubMed  Google Scholar 

  • Suzuki K, Shuto S, Miura Y et al (2008) Measurement of telomerase activity in bovine leukaemia virus infected cows. Vet Microbiol 127:142–146

    Article  CAS  PubMed  Google Scholar 

  • Szczotka M, Kuzmak J (2013) Telomerase activity and telomere length in cattle infected with bovine leukemia virus (Blv). J Comp Pathol 148:70–70

    Article  Google Scholar 

  • Tajima S, Zhuang WZ, Kato MV et al (1998) Function and conformation of wild-type p53 protein Are influenced by mutations in bovine leukemia virus-induced B-cell lymphosarcoma. Virology 243:235–246

    Article  CAS  PubMed  Google Scholar 

  • Tilesi F, Di Domenico EG, Pariset L et al (2010) Telomere length diversity in cattle breeds. Diversity 2:1118–1129

    Article  CAS  Google Scholar 

  • Vonderheide RH, Hahn WC, Schultze JL et al (1999) The telomerase catalytic subunit is a widely expressed tumor-associated antigen recognized by cytotoxic T lymphocytes. Immunity 10:673–679

    Article  CAS  PubMed  Google Scholar 

  • Zaghawa A, Beier D, Abd El-Rahim IH et al (2002) An outbreak of enzootic bovine leukosis in upper Egypt: clinical, laboratory and molecular-epidemiological studies. J Vet Med B Infect Dis Vet Public Health 49:123–129

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by funds provided by the University of Adelaide as well as a research grant obtained from the University of Tehran. The granting agencies had no role in study design, data collection and analysis or manuscript preparation. We would like to acknowledge Dr Taghi Taghipour Bazargani and Dr Reza Kasravi from The University of Tehran for their assistance with sample collection and case histories. We would also like to thank Ms Jessica Raven from the University of Adelaide for providing technical assistance.

Conflict of interest statement

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. School of Animal and Veterinary Science, The University of Adelaide, Adelaide, Australia

    Farhid Hemmatzadeh, Noor Haliza Hasan, Faustina Niap & Andrea McWhorter

  2. Faculty of Veterinary Medicine, The University of Tehran, Tehran, Iran

    Hadi Keyvanfar

  3. Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Melbourne, Australia

    Ebrahim Bani Hassan & Jagoda Ignjatovic

  4. Faculty of Agriculture and Animal Sciences, Islamic Azad University of Shahrekord, Shahrekord, Iran

    Azar Hematzade

  5. School of Molecular and Biomedical Science, The University of Adelaide, Adelaide, Australia

    Esmaeil Ebrahimie

Authors
  1. Farhid Hemmatzadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hadi Keyvanfar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Noor Haliza Hasan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Faustina Niap
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ebrahim Bani Hassan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Azar Hematzade
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Esmaeil Ebrahimie
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Andrea McWhorter
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jagoda Ignjatovic
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Farhid Hemmatzadeh.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hemmatzadeh, F., Keyvanfar, H., Hasan, N.H. et al. Interaction between Bovine leukemia virus (BLV) infection and age on telomerase misregulation. Vet Res Commun 39, 97–103 (2015). https://doi.org/10.1007/s11259-015-9629-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11259-015-9629-2

Keywords

Search

Navigation