IDEAS home Printed from https://ideas.repec.org/a/plo/pone00/0003486.html
   My bibliography  Save this article

The Evolutionary Selective Advantage of HIV-1 Escape Variants and the Contribution of Escape to the HLA-Associated Risk of AIDS Progression

Author

Listed:
  • Becca Asquith

Abstract

HIV-1 escape from surveillance by cytotoxic T lymphocytes (CTL) is thought to cause at least transient weakening of immune control. However, the CTL response is highly adaptable and the long-term consequences of viral escape are not fully understood. The objective of this study was to address the question “to what extent does HIV-1 escape from CTL contribute to HLA-associated AIDS progression?” We combined an analysis of 21 escape events in longitudinally-studied HIV-1 infected people with a population-level analysis of the functional CTL response in 150 subjects (by IFNg ELISpot) and an analysis of the HIV-1 sequence database to quantify the contribution of escape to the HLA-associated rate of AIDS progression. We found that CTL responses restricted by protective HLA class I alleles, which are associated with slow progression to AIDS, recognised epitopes where escape variants had a weak evolutionary selective advantage (P = 0.008) and occurred infrequently (P = 0.017). Epitopes presented by protective HLA class I alleles were more likely to elicit a CTL response (P = 0.001) and less likely to contain sequence variation (P = 0.006). A third of between-individual variation in HLA-associated disease risk was predicted by the selective advantage of escape variants: a doubling in the evolutionary selective advantage was associated with a decrease in the AIDS-free period of 1.2 yrs. These results contribute to our understanding of what makes a CTL response protective and why some individuals progress to AIDS more rapidly than others.

Suggested Citation

  • 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.
  • Handle: RePEc:plo:pone00:0003486
    DOI: 10.1371/journal.pone.0003486
    as

    Download full text from publisher

    File URL: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0003486
    Download Restriction: no

    File URL: https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0003486&type=printable
    Download Restriction: no

    File URL: https://libkey.io/10.1371/journal.pone.0003486?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Daniel C. Douek & Jason M. Brenchley & Michael R. Betts & David R. Ambrozak & Brenna J. Hill & Yukari Okamoto & Joseph P. Casazza & Janaki Kuruppu & Kevin Kunstman & Steven Wolinsky & Zvi Grossman & M, 2002. "HIV preferentially infects HIV-specific CD4+ T cells," Nature, Nature, vol. 417(6884), pages 95-98, May.
    2. Cheryl L. Day & Daniel E. Kaufmann & Photini Kiepiela & Julia A. Brown & Eshia S. Moodley & Sharon Reddy & Elizabeth W. Mackey & Joseph D. Miller & Alasdair J. Leslie & Chantal DePierres & Zenele Mncu, 2006. "PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression," Nature, Nature, vol. 443(7109), pages 350-354, September.
    3. 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.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. 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.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    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. Norma Rallón & Marcial García & Javier García-Samaniego & Alfonso Cabello & Beatriz Álvarez & Clara Restrepo & Sara Nistal & Miguel Górgolas & José M Benito, 2018. "Expression of PD-1 and Tim-3 markers of T-cell exhaustion is associated with CD4 dynamics during the course of untreated and treated HIV infection," PLOS ONE, Public Library of Science, vol. 13(3), pages 1-14, March.
    4. 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.
    5. 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.
    6. 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.
    7. Haibin Wang & Rui Xu, 2013. "Stability and Hopf Bifurcation in an HIV-1 Infection Model with Latently Infected Cells and Delayed Immune Response," Discrete Dynamics in Nature and Society, Hindawi, vol. 2013, pages 1-12, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:plo:pone00:0003486. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: plosone (email available below). General contact details of provider: https://journals.plos.org/plosone/ .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.