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HIV-1 Nef protein protects infected primary cells against killing by cytotoxic T lymphocytes

Nature volume 391, pages 397–401 (1998)Cite this article

Abstract

Cytotoxic T lymphocytes (CTLs) lyse virally infected cells that display viral peptide epitopes in association with major histocompatibility complex (MHC) class I molecules on the cell surface. However, despite a strong CTL response directed against viral epitopes, untreated people infected with the human immunodeficiency virus (HIV-1) develop AIDS. To resolve this enigma, we have examined the ability of CTLs to recognize and kill infected primary T lymphocytes. We found that CTLs inefficiently lysed primary cells infected with HIV-1 if the viral nef gene product was expressed. Resistance of infected cells to CTL killing correlated with nef-mediated downregulation of MHC class I (ref. 1) and could be overcome by adding an excess of the relevant HIV-1 epitope as soluble peptide. Thus, Nef protected infected cells by reducing the epitope density on their surface. This effect of nef may allow evasion of CTL lysis by HIV-1-infected cells.

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Figure 1: Genomic organization of HIV-1 vectors containing PLAP.
Figure 2: Flow-cytometric measurement of anti-HIV CTL-mediated cytotoxicity (clone 161XJA14).
Figure 3: Nef protects cells from killing by the gag-specific CTL clone 18030D23.
Figure 4: Nef protects cells from killing by CTL clone 161JXA14.
Figure 5: Cells infected with the NL-PI HIV-1 molecular clone are protected by Nef against CTL lysis, and CTL killing detected by cytofluorimetry is dependent on expression of the appropriate epitope.

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Acknowledgements

We thank H. Eisen, H. Ploegh, D. Camerini and members of D.B.'s laboratory; and A. K. Trocha, O. O. Yang, N. Jones and E. Rosenberg for help with culturing CTL clones, for chromium-release assays and for human lymphocytes. K.C. was the recipient of a Howard Hughes fellowship award for physicians. B.K.C. was supported by a Medical Scientist Training Program Award. D.B. is an American Cancer Society Research Professor. Supported at M.I.T. by funds from the Ivan R. Cottrell Chair and at M.G.H. by grants from the N.I.H.

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Author notes

  1. David Baltimore

    Present address: California Institute of Technology, Pasadena, California, 91125, USA

Authors and Affiliations

  1. Department of Biology, Massachusetts Institute of Technology, Cambridge, 02139, Massachusetts, USA

    Kathleen L. Collins & David Baltimore

  2. Combined Infectious Disease Training Program, Brigham and Women's Hospital, and Massachusetts General Hospital, Boston, 02115, Massachusetts, USA

    Kathleen L. Collins, Spyros A. Kalams & Bruce D. Walker

  3. Harvard Medical School, Boston, 02115, Massachusetts, USA

    Kathleen L. Collins

  4. AIDS Research Center and Infectious Disease Unit, Massachusetts General Hospital, Charlestown, 02129, Massachusetts, USA

    Benjamin K. Chen

  5. Rockefeller University, New York, 10021, New York, USA

    Spyros A. Kalams & Bruce D. Walker

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Correspondence to David Baltimore.

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Collins, K., Chen, B., Kalams, S. et al. HIV-1 Nef protein protects infected primary cells against killing by cytotoxic T lymphocytes. Nature 391, 397–401 (1998). https://doi.org/10.1038/34929

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