The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus

Abstract

Acquired immune deficiency syndrome (AIDS) is characterized by opportunistic infections and by ‘opportunistic neoplasms’ (for example, Kaposi's sarcoma)1. Persistent generalized lymphadenopathy (PGL) is epidemiologically associated with AIDS, especially in male homosexuals. A subset of T lymphocytes positive for the CD4 antigen2 (also termed T4 antigen), is depleted in AIDS and PGL patients. A retrovirus found in T-cell cultures from these patients3–5 is strongly implicated in the aetiology of AIDS because of the high frequency of isolation4 and the prevalence of specific antibodies6–8 in the patients. Here we have detected cell-surface receptors for the AIDS retrovirus (human T-cell leukaemia virus-III (HTLV-III) and lymphadenopathy-associated virus-1 (LAV-1) isolates) by testing the susceptibility of cells to infection with pseudotypes of vesicular stomatitis virus bearing retroviral envelope antigens, and by the formation of multinucleated syncytia on mixing virus-producing cells with receptor-bearing cells. Receptors were present only on cells expressing CD4 antigen; among 155 monoclonal antibodies tested, each of the 14 anti-CD4 antibodies inhibited formation of syncytia and blocked pseudotypes. Productive infection of CD4+ cells with HTLV-III or LAV-1 markedly reduced cell-surface expression of CD4. In contrast, receptors for HTLV-I and HTLV-II were not restricted to CD4+ cells, were not blocked by anti-CD4 antibodies; cells productively infected with HTLV-I and HTLV-II expressed surface CD4. Hence, we conclude that the CD4 antigen is an essential and specific component of the receptor for the causative agent of AIDS.

References

  1. 1

    Pinching, A. J. Clin. exp Immun. 56, 1–13 (1984).

    CAS  PubMed  Google Scholar 

  2. 2

    Terhost, C., van Agthoven, A., Reinherz, E. & Schlossman, S. Science 209, 520–521 (1980).

    ADS  Article  Google Scholar 

  3. 3

    Barré-Sinoussi, F. et al. Science 220, 868–870 (1983).

    ADS  Article  Google Scholar 

  4. 4

    Gallo, R. C. et al. Science 224, 500–503 (1984).

    ADS  CAS  Article  Google Scholar 

  5. 5

    Popovic, M., Sarngadharan, M. G., Read, E. & Gallo, R. C. Science 224, 497–500 (1984).

    ADS  CAS  Article  Google Scholar 

  6. 6

    Brun-Vezinet, F. et al. Lancet i, 1253–1256 (1984).

    Article  Google Scholar 

  7. 7

    Safai, B. et al. Lancet i, 1438–1440 (1984).

    Article  Google Scholar 

  8. 8

    Cheingsong-Popov, R. et al. Lancet ii, 477–480 (1984).

    Article  Google Scholar 

  9. 9

    Vilmer, E. et al. Lancet i, 753–757 (1984).

    Article  Google Scholar 

  10. 10

    Montagnier, L. et al. in Human T-cell Leukemia/Lymphoma Virus (eds Gallo, R. C., Essex, M. & Gross, L.) 363–379 (Cold Spring Harbor Laboratory, New York, 1984).

    Google Scholar 

  11. 11

    Schüpbach, J. et al. Science 224, 503–506 (1984).

    ADS  Article  Google Scholar 

  12. 12

    Arya, S. K. et al. Science 225, 927–980 (1984).

    ADS  CAS  Article  Google Scholar 

  13. 13

    Popovic, M. et al. Proc. natn. Acad. Sci. U.S.A. 80, 5402–5406 (1983).

    ADS  CAS  Article  Google Scholar 

  14. 14

    Chen, I. S. Y., Quan, S. G. & Golde, D. W. Proc. natn. Acad. Sci. U.S.A. 80, 7006–7009 (1983).

    ADS  CAS  Article  Google Scholar 

  15. 15

    Klatzmann, D. et al. Science 225, 59–63 (1984).

    ADS  CAS  Article  Google Scholar 

  16. 16

    Montagnier, L. et al. Science 225, 63–66 (1984).

    ADS  CAS  Article  Google Scholar 

  17. 17

    Clapham, P., Nagy, K., Cheingsong-Popov, R. & Weiss, R. A. Science 222, 1125–1127 (1983).

    ADS  CAS  Article  Google Scholar 

  18. 18

    Hoshino, H., Shimoyama, M., Miwa, M. & Sugimura, T. Proc. natn. Acad. Sci. U.S.A. 80, 7337–7341 (1983).

    ADS  CAS  Article  Google Scholar 

  19. 19

    Nagy, K., Clapham, P., Cheingsong-Popov, R. & Weiss, R. A. Int. J. Cancer 32, 321–328 (1983).

    CAS  Article  Google Scholar 

  20. 20

    Clapham, P., Nagy, K. & Weiss, R. A. Proc. natn. Acad. Sci. U.S.A. 81, 2886–2889 (1984).

    ADS  CAS  Article  Google Scholar 

  21. 21

    Zavada, J. J. gen. Virol. 15, 183–191 (1972).

    CAS  Article  Google Scholar 

  22. 22

    Boettiger, D., Love, D. N. & Weiss, R. A. J. Virol. 15, 108–114 (1975).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. 23

    Weiss, R. A. in Virus Receptors (eds Lonberg-Holm, K. & Philipson, L.) 186–202 (Chapman & Hall, London, 1981).

    Google Scholar 

  24. 24

    Thiry, L. et al. J. Virol. 48, 697–708 (1983).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. 25

    Klatzmann, D. et al. Nature 312, 767–771 (1984).

    ADS  CAS  Article  Google Scholar 

  26. 26

    Gatenby, P. A. et al. J. Immun. 129, 1997–2000 (1982).

    CAS  Google Scholar 

  27. 27

    Bernard, A. et al. (eds) Leucocyte Typing (Springer, Berlin, 1984).

    Google Scholar 

  28. 28

    Meuer, S. C., Schlossman, S. F. & Reinherz, E. L. Proc. natn. Acad. Sci. U.S.A. 79, 4395–4399 (1982).

    ADS  CAS  Article  Google Scholar 

  29. 29

    Biddison, W. E. et al. J. exp. Med. 159, 783–797 (1984).

    CAS  Article  Google Scholar 

  30. 30

    Nicholson, J. K. A. et al. J. clin. Invest. 73, 191–201 (1984).

    CAS  Article  Google Scholar 

  31. 31

    Sundström, C. & Nilsson, K. Int. J. Cancer 17, 565–577 (1976).

    Article  Google Scholar 

  32. 32

    Wood, G. S., Warner, N. L. & Warnke, R. A. J. Immun. 131, 212–216 (1983).

    CAS  PubMed  Google Scholar 

  33. 33

    Moscicki, R. A. et al. J. Immun. 131, 743–748 (1983).

    CAS  PubMed  Google Scholar 

  34. 34

    Fingeroth, J. D. et al. Proc. natn. Acad. Sci. U.S.A. 81, 4510–4514 (1984).

    ADS  CAS  Article  Google Scholar 

  35. 35

    Lentz, T. L. et al. Science 215, 182–184 (1982).

    ADS  CAS  Article  Google Scholar 

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Dalgleish, A., Beverley, P., Clapham, P. et al. The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature 312, 763–767 (1984). https://doi.org/10.1038/312763a0

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