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

Author

Listed:
  • Kathleen L. Collins

    (Massachusetts Institute of Technology
    Combined Infectious Disease Training Program, Brigham and Women's Hospital, and Massachusetts General Hospital
    Harvard Medical School)

  • Benjamin K. Chen

    (AIDS Research Center and Infectious Disease Unit, Massachusetts General Hospital)

  • Spyros A. Kalams

    (Combined Infectious Disease Training Program, Brigham and Women's Hospital, and Massachusetts General Hospital
    Rockefeller University)

  • Bruce D. Walker

    (Combined Infectious Disease Training Program, Brigham and Women's Hospital, and Massachusetts General Hospital
    Rockefeller University)

  • David Baltimore

    (Massachusetts Institute of Technology
    California Institute of Technology)

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.

Suggested Citation

  • Kathleen L. Collins & Benjamin K. Chen & Spyros A. Kalams & Bruce D. Walker & David Baltimore, 1998. "HIV-1 Nef protein protects infected primary cells against killing by cytotoxic T lymphocytes," Nature, Nature, vol. 391(6665), pages 397-401, January.
    • Handle: RePEc:nat:nature:v:391:y:1998:i:6665:d:10.1038_34929
    DOI: 10.1038/34929
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    Cited by:

    1. Eva M. Stevenson & Sandra Terry & Dennis Copertino & Louise Leyre & Ali Danesh & Jared Weiler & Adam R. Ward & Pragya Khadka & Evan McNeil & Kevin Bernard & Itzayana G. Miller & Grant B. Ellsworth & C, 2022. "SARS CoV-2 mRNA vaccination exposes latent HIV to Nef-specific CD8+ T-cells," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    2. Benjamin B. Policicchio & Erwing Fabian Cardozo-Ojeda & Cuiling Xu & Dongzhu Ma & Tianyu He & Kevin D. Raehtz & Ranjit Sivanandham & Adam J. Kleinman & Alan S. Perelson & Cristian Apetrei & Ivona Pand, 2023. "CD8+ T cells control SIV infection using both cytolytic effects and non-cytolytic suppression of virus production," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    3. Bernhard Konrad & Naveen Vaidya & Robert Smith?, 2011. "Modelling Mutation to a Cytotoxic T-lymphocyte HIV Vaccine," Mathematical Population Studies, Taylor & Francis Journals, vol. 18(2), pages 122-149.
    4. Ulrich D Kadolsky & Becca Asquith, 2010. "Quantifying the Impact of Human Immunodeficiency Virus-1 Escape From Cytotoxic T-Lymphocytes," PLOS Computational Biology, Public Library of Science, vol. 6(11), pages 1-11, November.
    5. Becca Asquith, 2008. "The Evolutionary Selective Advantage of HIV-1 Escape Variants and the Contribution of Escape to the HLA-Associated Risk of AIDS Progression," PLOS ONE, Public Library of Science, vol. 3(10), pages 1-10, October.
    6. Nathaniel D Bachtel & Gisele Umviligihozo & Suzanne Pickering & Talia M Mota & Hua Liang & Gregory Q Del Prete & Pramita Chatterjee & Guinevere Q Lee & Rasmi Thomas & Mark A Brockman & Stuart Neil & M, 2018. "HLA-C downregulation by HIV-1 adapts to host HLA genotype," PLOS Pathogens, Public Library of Science, vol. 14(9), pages 1-25, September.

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