IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-48985-9.html
   My bibliography  Save this article

HIV-1 subtype A1, D, and recombinant proviral genome landscapes during long-term suppressive therapy

Author

Listed:
  • Guinevere Q. Lee

    (Weill Cornell Medicine)

  • Pragya Khadka

    (Weill Cornell Medicine)

  • Sarah N. Gowanlock

    (Western University)

  • Dennis C. Copertino

    (Weill Cornell Medicine)

  • Maggie C. Duncan

    (Simon Fraser University
    British Columbia Centre for Excellence in HIV/AIDS)

  • F. Harrison Omondi

    (Simon Fraser University
    British Columbia Centre for Excellence in HIV/AIDS)

  • Natalie N. Kinloch

    (Simon Fraser University
    British Columbia Centre for Excellence in HIV/AIDS)

  • Jingo Kasule

    (Rakai Health Sciences Program)

  • Taddeo Kityamuweesi

    (Rakai Health Sciences Program)

  • Paul Buule

    (Rakai Health Sciences Program)

  • Samiri Jamiru

    (Rakai Health Sciences Program)

  • Stephen Tomusange

    (Rakai Health Sciences Program)

  • Aggrey Anok

    (Rakai Health Sciences Program)

  • Zhengming Chen

    (Weill Cornell Medicine)

  • R. Brad Jones

    (Weill Cornell Medicine)

  • Ronald M. Galiwango

    (Rakai Health Sciences Program)

  • Steven J. Reynolds

    (Rakai Health Sciences Program
    National Institute of Allergy and Infectious Diseases, National Institutes of Health
    Johns Hopkins University School of Medicine)

  • Thomas C. Quinn

    (National Institute of Allergy and Infectious Diseases, National Institutes of Health
    Johns Hopkins University School of Medicine)

  • Zabrina L. Brumme

    (Simon Fraser University
    British Columbia Centre for Excellence in HIV/AIDS)

  • Andrew D. Redd

    (National Institute of Allergy and Infectious Diseases, National Institutes of Health
    Johns Hopkins University School of Medicine
    University of Cape Town)

  • Jessica L. Prodger

    (Western University
    Western University)

Abstract

The primary obstacle to curing HIV-1 is a reservoir of CD4+ cells that contain stably integrated provirus. Previous studies characterizing the proviral landscape, which have been predominantly conducted in males in the United States and Europe living with HIV-1 subtype B, have revealed that most proviruses that persist during antiretroviral therapy (ART) are defective. In contrast, less is known about proviral landscapes in females with non-B subtypes, which represents the largest group of individuals living with HIV-1. Here, we analyze genomic DNA from resting CD4+ T-cells from 16 female and seven male Ugandans with HIV-1 receiving suppressive ART (n = 23). We perform near-full-length proviral sequencing at limiting dilution to examine the proviral genetic landscape, yielding 607 HIV-1 subtype A1, D, and recombinant proviral sequences (mean 26/person). We observe that intact genomes are relatively rare and clonal expansion occurs in both intact and defective genomes. Our modification of the primers and probes of the Intact Proviral DNA Assay (IPDA), developed for subtype B, rescues intact provirus detection in Ugandan samples for which the original IPDA fails. This work will facilitate research on HIV-1 persistence and cure strategies in Africa, where the burden of HIV-1 is heaviest.

Suggested Citation

  • Guinevere Q. Lee & Pragya Khadka & Sarah N. Gowanlock & Dennis C. Copertino & Maggie C. Duncan & F. Harrison Omondi & Natalie N. Kinloch & Jingo Kasule & Taddeo Kityamuweesi & Paul Buule & Samiri Jami, 2024. "HIV-1 subtype A1, D, and recombinant proviral genome landscapes during long-term suppressive therapy," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48985-9
    DOI: 10.1038/s41467-024-48985-9
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-48985-9
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-48985-9?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. Katherine M. Bruner & Zheng Wang & Francesco R. Simonetti & Alexandra M. Bender & Kyungyoon J. Kwon & Srona Sengupta & Emily J. Fray & Subul A. Beg & Annukka A. R. Antar & Katharine M. Jenike & Lynn N, 2019. "A quantitative approach for measuring the reservoir of latent HIV-1 proviruses," Nature, Nature, vol. 566(7742), pages 120-125, February.
    2. Guinevere Q. Lee & Kavidha Reddy & Kevin B. Einkauf & Kamini Gounder & Joshua M. Chevalier & Krista L. Dong & Bruce D. Walker & Xu G. Yu & Thumbi Ndung’u & Mathias Lichterfeld, 2019. "HIV-1 DNA sequence diversity and evolution during acute subtype C infection," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    Full references (including those not matched with items on IDEAS)

    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. González, Ramón E.R. & Figueirêdo, P.H. & Coutinho, S., 2020. "Dynamics of HIV Infection: An entropic–energetic view," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 551(C).
    3. Miriam Rosás-Umbert & Jesper D. Gunst & Marie H. Pahus & Rikke Olesen & Mariane Schleimann & Paul W. Denton & Victor Ramos & Adam Ward & Natalie N. Kinloch & Dennis C. Copertino & Tuixent Escribà & An, 2022. "Administration of broadly neutralizing anti-HIV-1 antibodies at ART initiation maintains long-term CD8+ T cell immunity," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    4. Caroline Dufour & Corentin Richard & Marion Pardons & Marta Massanella & Antoine Ackaoui & Ben Murrell & Bertrand Routy & Réjean Thomas & Jean-Pierre Routy & Rémi Fromentin & Nicolas Chomont, 2023. "Phenotypic characterization of single CD4+ T cells harboring genetically intact and inducible HIV genomes," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    5. Fredrick Otieno Oginga & Felisters Akal Edung & Vasco Dominic Kulimankudya & Brenda Lijodi & Jeremiah Motari & Charles Stephen Okila, 2024. "Advancements in HIV/AIDS Cure Research: Effects on Patient Adherence and Behavioral Trends in the General Population a Scoping Review," International Journal of Research and Scientific Innovation, International Journal of Research and Scientific Innovation (IJRSI), vol. 11(10), pages 355-368, October.
    6. Daniel B. Reeves & Christian Gaebler & Thiago Y. Oliveira & Michael J. Peluso & Joshua T. Schiffer & Lillian B. Cohn & Steven G. Deeks & Michel C. Nussenzweig, 2023. "Impact of misclassified defective proviruses on HIV reservoir measurements," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    7. Daniel B. Reeves & Charline Bacchus-Souffan & Mark Fitch & Mohamed Abdel-Mohsen & Rebecca Hoh & Haelee Ahn & Mars Stone & Frederick Hecht & Jeffrey Martin & Steven G. Deeks & Marc K. Hellerstein & Jos, 2023. "Estimating the contribution of CD4 T cell subset proliferation and differentiation to HIV persistence," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    8. Catherine DeMarino & Julia Denniss & Maria Cowen & Gina Norato & Devon K. Dietrich & Lisa Henderson & Elyse Gollomp & Joseph Snow & Darshan Pandya & Bryan Smith & Avindra Nath, 2024. "HIV-1 RNA in extracellular vesicles is associated with neurocognitive outcomes," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    9. Aliu Oguntade Fatai & Raymond Osi Alenoghena, 2024. "The Role of Deposit Growth in The Productivity of Deposit Money Banks in Nigeria: Case Study of Union and Wema Banks in Lagos State," International Journal of Research and Scientific Innovation, International Journal of Research and Scientific Innovation (IJRSI), vol. 10(12), pages 234-246, January.
    10. Maria Pino & Amélie Pagliuzza & M. Betina Pampena & Claire Deleage & Elise G. Viox & Kevin Nguyen & Inbo Shim & Adam Zhang & Justin L. Harper & Sadia Samer & Colin T. King & Barbara Cervasi & Kiran P., 2022. "Limited impact of fingolimod treatment during the initial weeks of ART in SIV-infected rhesus macaques," Nature Communications, Nature, vol. 13(1), 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:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48985-9. 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: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    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.