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:

CD26 expression correlates with entry, replication and cytopathicity of monocytotropic HIV–1 strains in a T–cell line

Nature Medicine volume 1, pages 919–926 (1995)Cite this article

Abstract

Experiments to identify cell determinants involved in HIV-1 tropism revealed a specific decrease in the expression of the T–cell activation antigen CD26 after monocytotropic (M–tropic) but not T–cell line–tropic (T–tropic) virus infection of the PM1 T–cell line. The level of CD26 expression in single–cell clones of PM1 correlated with the entry rate and cytopathicity of M–tropic HIV–1 variants, resulting in preferential survival of cells with low CD26 levels after infection. Experiments with recombinant viruses showed that the third hypervariable region of the envelope gp120 plays an important role in this selection process. This study identifies CD26 as a key marker for M–tropic human immunodeficiency virus type 1 (HIV–1) infection and suggests a mechanism for the early loss of CD26–expressing cells in HIV–1–infected individuals.

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

Access options

Buy this article

  • Purchase on Springer Link
  • 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. Schuitemaker, H. et al. Biological phenotype of human immunodeficiency virus type-1 clones at different stages of infection: Progression of disease is associated with a shift from M-tropic to T-cell-tropic virus populations. J. Virol. 66, 1354–1360 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Koot, M. et al. HIV-1 Biological phenotype in long-term infected individuals evaluated with an MT-2 cocultivation assay. AIDS 6, 49–54 (1992).

    Article  CAS  PubMed  Google Scholar 

  3. Cheng-Mayer, C., Quiroga, M., Tung, J.W., Dina, D. & Levy, J.A. Viral determinants of human immunodeficiency virus type 1 T-cell or macrophage tropism, cytopathogenicity, and CD4 antigen modulation. J. Virol. 64, 4390–4398 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Bou-Habib, D.C. et al. Cryptic nature of envelope V3 region epitopes protects primary M-tropic human immunodeficiency virus type 1 from antibody neutralization. J. Virol. 68, 6006–6013 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Gruters, R.A. et al. Immunological and virological markers in individuals progressing from seroconversion to AIDS. AIDS 5, 837–844 (1991).

    Article  CAS  PubMed  Google Scholar 

  6. Zhu, T. et al. Genotypic and phenotypic characterization of HIV-1 patients with primary infection. Science 261, 1179–1181 (1993).

    Article  CAS  PubMed  Google Scholar 

  7. Cann, A.J. et al. The region of the envelope gene of human immunodeficiency virus type-1 responsible for determination of cell tropism. J. Virol. 66, 305–309 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Skinner, M.A. et al. Neutralizing antibodies to an immunodominant envelope sequence do not prevent gp120 binding to CD4. J. Virol. 62, 4195–4200 (1988).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. de Jong, J.J., de Ronde, A., Keulen, W., Tersmette, M. & Goudsmit, J. Minimal requirements for the human immunodeficiency virus type-1 V3 domain to support the syncytium-inducing phenotype: Analysis by single arhino acid substitution. J. Virol. 66, 6777–6780 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Roderiquez, G. et al. Mediation of human immunodeficiency virus type 1 binding by interaction of cell surface heparan sulfate proteoglycans with the V3 region of envelope gp120-gp41. J. Virol 69, 2233–2239 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Maddon, P.J. et al. The T4 gene encodes the AIDS virus receptor and is expressed in the immune system and the brain. Cell 47, 333–348 (1986).

    Article  CAS  PubMed  Google Scholar 

  12. Dragic, T., Charneau, P., Clavel, F. & Alizon, M. Complementation of murine cells for human immunodeficiency virus envelope/CD4-mediated fusion in human/murine heterokaryons. J. Virol. 66, 4794–4802 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Blazquez, M.V. et al. Selective decrease of CD26 expression in T-cells from HIV-1-infected individuals. J. Immun. 149, 3073–3077 (1992).

    CAS  PubMed  Google Scholar 

  14. Callebaut, C., Krust, B., Jacotot, E. & Hovanessian, A.G. T cell activation antigen, CD26, as a cofactor for entry of HIV in CD4+ cells. Science 262, 2045–2050 (1993).

    Article  CAS  PubMed  Google Scholar 

  15. Vanham, G. et al. Decreased expression of the memory marker CD26 on both CD4+ and CD8+ T lymphocytes of HIV-infected subjects. J. acquir. immun. Defic. Syndr. 6, 749–757 (1993).

    CAS  Google Scholar 

  16. Callebaut, C., Jacotot, E., Krust, B. & Havanessian, A.G. CD26 antigen and HIV fusion? [Response] Science 264, 1162–1165 (1994).

    Article  CAS  PubMed  Google Scholar 

  17. Broder, C.C. et al; Patience, C. et al; Camerini, D. et al; & Alizon, M. et al. CD26 antigen and HIV fusion? [Technical Comments] Science 264, 1156–1162 (1994).

    Article  CAS  PubMed  Google Scholar 

  18. Lazaro, I. et al. Factors involved in entry of the human immunodeficiency virus type 1 into permissive cells: Lack of evidence of a role for CD26. J. Virol 68, 6535–6546 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Morimoto, C. et al. Role of CD26/dipeptidyl peptidase IV in human immunodeficiency virus type 1 infection and apoptosis. Proc. natn. Acad. Sci. U.S.A. 91, 9960–9964 (1994).

    Article  CAS  Google Scholar 

  20. Hildreth, J.E. & Orentas, R.J. Involvement of a leukocyte adhesion receptor (LFA-1) in HIV-induced syncytium formation. Science 244, 1075–1078 (1989).

    Article  CAS  PubMed  Google Scholar 

  21. Kido, H., Fukutomi, A. & Katunuma, N. A novel membrane-bound serine esterase in human T4+ lymphocytes immunologically reactive with antibody inhibiting syncytia induced by HIV-1. Purification and characterization. J. biol. Chem. 265, 21979–21985 (1990).

    CAS  PubMed  Google Scholar 

  22. Meerloo, T., Parmentier, H.K., Osterhaus, A.D.M.E., Goudsmit, J. & Schuurman, H.J. Modulation of cell surface molecules during HIV-1 infection of H9 cells: An immunoelectron microscopic study. AIDS 6, 1105–1116 (1992).

    Article  CAS  PubMed  Google Scholar 

  23. Lusso, P. et al. Growth of macrophage-tropic and primary human immunodeficiency virus type 1 (HIV-1) isolates in a unique CD4+ T-cell clone (PM1): Failure to downregulate CD4 and to interfere with cell-line-tropic HIV-1. J. Virol 69, 3712–3720 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Ansorge, S. & Schön, E. Dipeptidyl peptidase IV in human T lymphocytes: an approach to the function of this peptidase in the immune system. Adv. Biosci. 3–10 (1987).

  25. Bednarczyk, J.L., Carroll, S.M., Marin, C. & Mclntyre, B.W. Triggering of the proteinase dipeptidyl peptidase IV (CD26) amplifies human T lymphocyte proliferation. J. cell Biochem. 46, 206–218 (1991).

    Article  CAS  PubMed  Google Scholar 

  26. Tanaka, T. et al. Cloning and functional expression of the T cell activation antigen CD26. J. Immun. 149, 481–486 (1992).

    CAS  PubMed  Google Scholar 

  27. Hoxie, J.A. et al. Alterations in T4 (CD4) protein and mRNA synthesis in cells infected with HIV. Science 234, 1123–1127 (1986).

    Article  CAS  PubMed  Google Scholar 

  28. Serpente, N. et al. Transcriptional and post-transcriptional mechanisms are involved in the absence of CD4 surface expression in two HIV-1 chronically infected T cell lines. Int. Immun. 5, 939–947 (1993).

    Article  CAS  PubMed  Google Scholar 

  29. Cann, A.J. et al. Human immunodeficiency virus type 1 T-cell tropism is determined by events prior to provirus formation. J. Virol 64, 4735–4742 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Clements, G.J. et al. The V3 loops of the HIV-1 and HIV-2 surface glycoproteins contain proteolytic cleavage sites: A possible function in viral fusion? AIDS Res. hum. Retrovir. 7, 3–16 (1991).

    Article  CAS  PubMed  Google Scholar 

  31. Torimoto, Y. et al. Coassociation of CD26 (dipeptidyl peptidase IV) with CD45 on the surface of human T lymphocytes. J. Immun. 147, 2514–2517 (1991).

    CAS  PubMed  Google Scholar 

  32. Kameoka, J., Tanaka, T., Nojima, Y., Schlossman, S.F. & Morimoto, C. Direct association of adenosine deaminase with a T cell activation antigen, CD26. Science 261, 466–469 (1993).

    Article  CAS  PubMed  Google Scholar 

  33. Gutheil, W.G. et al. Human immunodeficiency virus 1 Tat binds to dipeptidyl aminopeptidase IV (CD26): A possible mechanism for Tat's immunosuppressive activity. Proc. natn. Acad. Sci. U.S.A. 91, 6594–6598 (1994).

    Article  CAS  Google Scholar 

  34. Hafler, D.A., Fox, D.A., Benjamin, D. & Weiner, H.L. Antigen reactive memory T cells are defined by Tal. J. Immun. 137, 414–418 (1986).

    CAS  PubMed  Google Scholar 

  35. Clerici, M. et al. Restoration of HIV-specific cell-mediated immune responses by interleukin-12 in vitro. Science 262, 1721–1724 (1993).

    Article  CAS  PubMed  Google Scholar 

  36. Ratner, L. et al. Complete nucleotide sequence of the AIDS virus, HTLV-III. Nature 313, 277–284 (1985).

    Article  CAS  PubMed  Google Scholar 

  37. Gartner, S. et al. The role of mononuclear phagocytes in HTLV-III/LAV infection. Science 233, 215–219 (1986).

    Article  CAS  PubMed  Google Scholar 

  38. Gallo, R.C. et al. Frequent detection and isolation of cytopathic retroviruses (HTLV-III) from patients with AIDS and at risk for AIDS. Science 224, 500–503 (1984).

    Article  CAS  PubMed  Google Scholar 

  39. Koyanagi, Y. et al. Dual infection of the central nervous system by AIDS viruses with distinct cellular tropisms. Science 236, 819–822 (1987).

    Article  CAS  PubMed  Google Scholar 

  40. Patel, M. et al. Cell-surface heparan sulfate proteoglycan mediates HIV-1 infection of T-cell lines. AIDS Res. hum. Retrovir. 9, 167–174 (1993).

    Article  CAS  PubMed  Google Scholar 

  41. Oravecz, T. & Norcross, M.A. Costimulatory properties of the human CD4 molecule: Enhancement of CD3-induced T cell activation by human immunodeficiency virus type 1 through viral envelope glycoprotein gp120. AIDS Res. hum. Retrovir. 9, 945–955 (1993).

    Article  CAS  PubMed  Google Scholar 

  42. Oravecz, T., Monostori, É., Kurucz, É., Takács, L. & Andó, I., T-cell proliferation and interleukin-2 secretion is modulated by the CD45 antigen. Scand. J. Immun. 34, 531–537 (1991).

    Article  CAS  Google Scholar 

  43. Oravecz, T., Monostori, É., Adrian, O., Kurucz, É. & Andó, I. Novel heterogeneity of the leucocyte common antigen (CD45): Disulfide-bound heterodimers between CD45 and an 80 kDa polypeptide. Immun. Lett. 40, 7–11 (1994).

    Article  CAS  Google Scholar 

  44. Maniatis, T., Fritsch, E.F. & Sambrook, J. Molecular Cloning: A Laboratory Manual (Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, 1982).

    Google Scholar 

  45. Folks, T.M. et al. Biological and biochemical characterization of a cloned Leu-3-cell surviving infection with the acquired immune deficiency syndrome retro-virus. J. exp. Med. 164, 280–290 (1986).

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Hematologic Products, Center for Biologies Evaluation and Research, Food and Drug Administration, National Institutes of Health, Building 29B, Room 4E12, HFM-541, Bethesda, Maryland, 20892, USA

    Tamás Oravecz, Gregory Roderiquez, Justin Koffi, Jinhai Wang, Mary Ditto, Dumith Chequer Bou-Habib & Michael A. Norcross

  2. Instituto delle Malattie Infettive Università di Milano, Ospedale L. Sacco, 20132, Milano, Italy

    Paolo Lusso

Authors
  1. Tamás Oravecz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gregory Roderiquez
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Justin Koffi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jinhai Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mary Ditto
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Dumith Chequer Bou-Habib
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Paolo Lusso
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Michael A. Norcross
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Oravecz, T., Roderiquez, G., Koffi, J. et al. CD26 expression correlates with entry, replication and cytopathicity of monocytotropic HIV–1 strains in a T–cell line. Nat Med 1, 919–926 (1995). https://doi.org/10.1038/nm0995-919

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nm0995-919

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