Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Antigenic stimulation by BCG vaccine as an in vivo driving force for SIV replication and dissemination

Nature Medicine volume 4, pages 421–427 (1998)Cite this article

Abstract

The impact of antigenic stimulation on the dynamics of simian immunodeficiency virus (SIV) replication was studied following repeated intravenous BCC inoculation of a SIV infected macaque. At the site of a delayed type hypersensitivity reaction to purified protein derivative of M. tuberculosis, a distinctive SIV variant was noted, probably as a result of the infiltration of activated antigen-specific T cell clones as opposed to infection by blood borne virus in situ. The dynamics of SIV quasispecies in peripheral blood suggests sequential waves of viral replication, illustrating the role of antigenic stimulation as a driving force in viral dissemination and pathogenesis.

Access through your institution
Buy or subscribe

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Mcliroy, D. et al. Infection frequency of dendritic cells and CD4+ T lymphocytes in spleens of human immunodeficiency virus-positive patients. J. Virol. 69, 4737–4745 (1995).

    Google Scholar 

  2. Schnittman, S.M. et al. Preferential infection of CD4+ memory T cells by human immunodeficiency virus type 1: evidence for a role in the selective T-cell functional defects observed in infected individuals. Proc. Natl. Acad. Sci. USA 87, 6058–62 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Zack, J.A., et al. HIV-1 entry into quiescent primary lymphocytes: molecular analysis reveals a labile, latent viral structure. Cell 61, 213–222 (1990).

    Article  CAS  PubMed  Google Scholar 

  4. Gaynor, R.B. Regulation of HIV-1 gene expression by the transactivator protein. Curr. Top. Microbiol. Immunol. 193, 51–77 (1995).

    CAS  PubMed  Google Scholar 

  5. Claydon, E.J., Bennett, J., Gor, D. & Forster, S.M. Transient elevation of serum HIV-1 antigen levels associated with intercurrent infection. AIDS 5, 113–114 (1991).

    Article  CAS  PubMed  Google Scholar 

  6. Fultz, P.N., Cluckman, J.C., Muchmore, E. & Girard, M. Transient increases in numbers of infectious cells in an HIV-1 infected chimpanzee following immune activation. AIDS Res. Hum. Retroviruses 8, 313–317 (1992).

    Article  CAS  PubMed  Google Scholar 

  7. Brichacek, B., Swindells, S., Janoff, E.N., Pirruccello, S. & Stevenson, M. Increased plasma human immunodeficiency virus type 1 burden following antigenic challenge with pneumococcal vaccine. J. Infect. Dis. 174,1191–9(1996).

    Article  CAS  PubMed  Google Scholar 

  8. Ho, D.D. HIV-1 viremia and influenza. Lancet 339, 1549 (1992).

    Article  CAS  PubMed  Google Scholar 

  9. O'Brien, W.A. et al. Human immunodeficiency virus type 1 replication can be increased in peripheral blood of seropositive patients after influenza vaccination. Blood 86, 1082–1089 (1995).

    CAS  PubMed  Google Scholar 

  10. Stanley, S.K. et al. Effect of immunization with a common recall antigen on viral expression in patients infected with human immunodeficiency virus type 1. N. Engl. J. Med. 334, 1222–1230 (1996).

    Article  CAS  PubMed  Google Scholar 

  11. Staprans, S.I. et al. Activation of virus replication after vaccination of HIV-1 infected individuals. J. Exp. Med. 182, 1727–1737 (1995).

    Article  CAS  PubMed  Google Scholar 

  12. Cheynier, R. et al. HIV and T cell expansion in splenic white pulps is accompanied by infiltration of HIV-specific cytotoxic T lymphocytes. Cell 78, 373–387 (1994).

    Article  CAS  PubMed  Google Scholar 

  13. Levy, J.A. The value of primate models for studying human immunodeficiency virus pathogenesis. J. Med. Primatol. 25, 163–174 (1996).

    Article  CAS  PubMed  Google Scholar 

  14. Pelletier, E., Saurin, W., Cheynier, R., Letvin, N.L. & Wain-Hobson, S. The tempo and mode of SIV quasispecies development in vivo calls for massive viral replication and clearance. Virology 208, 644–652 (1995).

    Article  CAS  PubMed  Google Scholar 

  15. Wain-Hobson, S. Viral burden and AIDS. Nature 366, 22 (1993).

    Article  CAS  PubMed  Google Scholar 

  16. Burns, D.P.W. & Desrosiers, R.C. Selection of genetic variants of simian immunodeficiency virus in persistently infected rhesus monkeys. J. Virol. 65, 1843–1854 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Kuramoto, Y., Sekita, Y. & Tagami, H. Histoanalytical study of the cellular infiltrate in the tuberculin reaction. Clin. Exp. Dermatol. 18, 111–118 (1993).

    Article  CAS  PubMed  Google Scholar 

  18. Bleavins, M.R. & DelaIglesia, F.A. Cynomologous monkeys (Macaco fascicularis) in preclinical immune function safety testing: development of a delayed-type hyper-sensitivity procedure. Toxicology 95, 103–112 (1995).

    Article  CAS  PubMed  Google Scholar 

  19. Pilkington, C., Costello, A.M., Rook, C.A. & Stanford, J.L. Development of IgC responses to mycobacterial antigens. Arch. Dis. Child. 69, 644–9 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Rota, S., Beyazova, U., Karsligil, T. & Cevheroglu, C. Humoral immune response against antigen 60 in BCG-vaccinated infants. Eur. J. Epidemiol. 10, 713–718 (1994).

    Article  CAS  PubMed  Google Scholar 

  21. Chen, Z.W., Yamamoto, H., Watkins, D.I., Levinson, G. & Letvin, N.L. Predominant use of a T-cell receptor Vβ gene family in simian immunodeficiency virus gag-specific cytotoxic T lymphocytes in a rhesus monkey. J. Virol. 66, 3913–3917 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Chen, Z.W., Kou, Z.-C., Shen, L., Reimann, K.A. & Letvin, N.L. Conserved T-cell receptor repertoire in simian immunodeficiency virus-infected rhesus monkeys. J. Immunol. 151, 2177–2187 (1993).

    CAS  PubMed  Google Scholar 

  23. Bandelt, H.J. & Dress, A.W.M. Split decomposition: a new and useful approach to phylogenetic analysis of distance data. Mol. Phylogenet. Evol. 1, 242–252 (1992).

    Article  CAS  PubMed  Google Scholar 

  24. Dopazo, J., Dress, A.W.M. & von Haeseler, A. Split decomposition: a new technique to analyse viral evolution. Proc. Natl. Acad. Sci. USA 90, 10320–10324 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Mansky, L.M. & Temin, H.M. Lower in vivo mutation rate of human immunodeficiency virus type 1 than that predicted from the fidelity of purified reverse transcriptase. J. Virol. 69, 5087–5094 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Ravn, P., Boesen, H., Pedersen, B.K. & Andersen, P. Human T cell responses induced by vaccination with Mycobacterium bovis Bacillus Calmette-Guérin. J. Virol. 158, 1949–1955 (1997).

    CAS  Google Scholar 

  27. Weissman, D., Barker, T.D. & Fauci, A.S. The efficiency of acute infection of CD4+ T cells is markedly enhanced in the setting of antigen-specific immune activation. J. Exp. Med. 183, 687–692 (1996).

    Article  CAS  PubMed  Google Scholar 

  28. Dittmer, U., Niblein, T., Meyerhans, A., Hunsmann, G. & Stahl-Henning, C. No reactivation of attenuated immunodeficiency viruses in macaques after vaccinia virus-induced immune activation. J. Cen. Virol. 78, 2523–2528 (1997).

    Article  CAS  Google Scholar 

  29. Kreiss, J. et al. Association between cervical inflammation and cervical shedding of human immunodeficiency virus DNA. J. Infect. Dis. 170, 1597–1601 (1994).

    Article  CAS  PubMed  Google Scholar 

  30. Galai, N., Kalinkovich, A., Burstein, R., Vlahov, D. & Bentwich, Z. African HIV-1 subtype C and rate of progression among Ethiopian immigrants in Israel. Lancet 349, 180–181 (1997).

    Article  CAS  PubMed  Google Scholar 

  31. Bentwich, Z., Kalinkovich, A. & Weisman, Z. Immune activation is a dominant factor in the pathogenesis of African AIDS. Immunol. Today 16, 187–191 (1995).

    Article  CAS  PubMed  Google Scholar 

  32. Gerna, G. et al. Sharp drop in the prevelance of human cytomegalovirus leuko-DNAemia in HIV-infected patients following highly active antiretroviral therapy. AIDS 12, 118–119 (1998).

    CAS  PubMed  Google Scholar 

  33. Chun, T.-W. et al. Quantitation of latent tissue reservoirs and total body viral load in HIV-1 infection. Nature 387, 183–188 (1997).

    Article  CAS  PubMed  Google Scholar 

  34. Finzi, D. et al. Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy. Science 278, 1295–1300 (1997).

    Article  CAS  PubMed  Google Scholar 

  35. Perelson, A.S. et al. Decay characteristics of HIV-1 infected conpartments and implications for eradication. Nature 387,188–191 (1997).

    Article  CAS  PubMed  Google Scholar 

  36. Wong, J.K. et al. Recovery of replication-competent HIV despite prolonged suppression of plasma viremia. Science 278, 1291–1295 (1997).

    Article  CAS  PubMed  Google Scholar 

  37. Cheynier, R., Henrichwark, S. & Wain-Hobson, S. Sequence of the rhesus monkey T-cell receptor β chain diversity and joining loci. Immunogenet. 43, 83–87 (1996).

    CAS  Google Scholar 

  38. Cheng, S., Fockler, C., Barnes, W.M. & Higuchi, R. Effective amplification of long targets from cloned inserts and human genomic DNA. Proc. Natl. Acad. Sci. USA 91, 5695–5699 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Author notes

  1. Ingrid Stahmer

    Present address: University Hospital Eppendorf, Dept. Immunology, Martinistr. 52, D-20246, Hamburg

  2. Rémi Cheynier and Sophie Gratton: Rémi Cheynier and Sophie Gratton contributed equally to this work.

Authors and Affiliations

  1. Unité de Rétrovirologie Moléculaire, Institut Pasteur, 28 Rue du Dr. Roux, 75724, Paris, cedex 15

    Rémi Cheynier, Sophie Gratton, Ingrid Stahmer & Simon Wain-Hobson

  2. Harvard Medical School, Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA, 02215

    Matilda Halloran & Norman L. Letvin

Authors
  1. Rémi Cheynier
    View author publications

    Search author on:PubMed Google Scholar

  2. Sophie Gratton
    View author publications

    Search author on:PubMed Google Scholar

  3. Matilda Halloran
    View author publications

    Search author on:PubMed Google Scholar

  4. Ingrid Stahmer
    View author publications

    Search author on:PubMed Google Scholar

  5. Norman L. Letvin
    View author publications

    Search author on:PubMed Google Scholar

  6. Simon Wain-Hobson
    View author publications

    Search author on:PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cheynier, R., Gratton, S., Halloran, M. et al. Antigenic stimulation by BCG vaccine as an in vivo driving force for SIV replication and dissemination. Nat Med 4, 421–427 (1998). https://doi.org/10.1038/nm0498-421

Download citation

  • Received:

  • Accepted:

  • Issue date:

  • DOI: https://doi.org/10.1038/nm0498-421

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing