IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-31692-8.html
   My bibliography  Save this article

CD8 lymphocytes mitigate HIV-1 persistence in lymph node follicular helper T cells during hyperacute-treated infection

Author

Listed:
  • Omolara O. Baiyegunhi

    (Africa Health Research Institute (AHRI)
    The Doris Duke Medical Research Institute, University of KwaZulu-Natal)

  • Jaclyn Mann

    (The Doris Duke Medical Research Institute, University of KwaZulu-Natal)

  • Trevor Khaba

    (The Doris Duke Medical Research Institute, University of KwaZulu-Natal)

  • Thandeka Nkosi

    (Africa Health Research Institute (AHRI))

  • Anele Mbatha

    (The Doris Duke Medical Research Institute, University of KwaZulu-Natal)

  • Funsho Ogunshola

    (Africa Health Research Institute (AHRI)
    Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University)

  • Caroline Chasara

    (Africa Health Research Institute (AHRI))

  • Nasreen Ismail

    (The Doris Duke Medical Research Institute, University of KwaZulu-Natal)

  • Thandekile Ngubane

    (The Doris Duke Medical Research Institute, University of KwaZulu-Natal)

  • Ismail Jajbhay

    (Prince Mshiyeni Memorial Hospital)

  • Johan Pansegrouw

    (Prince Mshiyeni Memorial Hospital)

  • Krista L. Dong

    (Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University)

  • Bruce D. Walker

    (Africa Health Research Institute (AHRI)
    The Doris Duke Medical Research Institute, University of KwaZulu-Natal
    Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University
    Institute for Medical Sciences and Engineering and Department of Biology, Massachusetts Institute of Technology)

  • Thumbi Ndung’u

    (Africa Health Research Institute (AHRI)
    The Doris Duke Medical Research Institute, University of KwaZulu-Natal
    Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University
    Max Planck Institute for Infection Biology)

  • Zaza M. Ndhlovu

    (Africa Health Research Institute (AHRI)
    The Doris Duke Medical Research Institute, University of KwaZulu-Natal
    Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University)

Abstract

HIV persistence in tissue sites despite ART is a major barrier to HIV cure. Detailed studies of HIV-infected cells and immune responses in native lymph node tissue environment is critical for gaining insight into immune mechanisms impacting HIV persistence and clearance in tissue sanctuary sites. We compared HIV persistence and HIV-specific T cell responses in lymph node biopsies obtained from 14 individuals who initiated therapy in Fiebig stages I/II, 5 persons treated in Fiebig stages III-V and 17 late treated individuals who initiated ART in Fiebig VI and beyond. Using multicolor immunofluorescence staining and in situ hybridization, we detect HIV RNA and/or protein in 12 of 14 Fiebig I/II treated persons on suppressive therapy for 1 to 55 months, and in late treated persons with persistent antigens. CXCR3+ T follicular helper cells harbor the greatest amounts of gag mRNA transcripts. Notably, HIV-specific CD8+ T cells responses are associated with lower HIV antigen burden, suggesting that these responses may contribute to HIV suppression in lymph nodes during therapy. These results reveal HIV persistence despite the initiation of ART in hyperacute infection and highlight the contribution of virus-specific responses to HIV suppression in tissue sanctuaries during suppressive ART.

Suggested Citation

  • Omolara O. Baiyegunhi & Jaclyn Mann & Trevor Khaba & Thandeka Nkosi & Anele Mbatha & Funsho Ogunshola & Caroline Chasara & Nasreen Ismail & Thandekile Ngubane & Ismail Jajbhay & Johan Pansegrouw & Kri, 2022. "CD8 lymphocytes mitigate HIV-1 persistence in lymph node follicular helper T cells during hyperacute-treated infection," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31692-8
    DOI: 10.1038/s41467-022-31692-8
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-31692-8
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-022-31692-8?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. Johannes F. Scheid & Joshua A. Horwitz & Yotam Bar-On & Edward F. Kreider & Ching-Lan Lu & Julio C. C. Lorenzi & Anna Feldmann & Malte Braunschweig & Lilian Nogueira & Thiago Oliveira & Irina Shimelio, 2016. "HIV-1 antibody 3BNC117 suppresses viral rebound in humans during treatment interruption," Nature, Nature, vol. 535(7613), pages 556-560, July.
    2. Ramon Lorenzo-Redondo & Helen R. Fryer & Trevor Bedford & Eun-Young Kim & John Archer & Sergei L. Kosakovsky Pond & Yoon-Seok Chung & Sudhir Penugonda & Jeffrey G. Chipman & Courtney V. Fletcher & Tim, 2016. "Persistent HIV-1 replication maintains the tissue reservoir during therapy," Nature, Nature, vol. 530(7588), pages 51-56, February.
    3. James B. Whitney & Alison L. Hill & Srisowmya Sanisetty & Pablo Penaloza-MacMaster & Jinyan Liu & Mayuri Shetty & Lily Parenteau & Crystal Cabral & Jennifer Shields & Stephen Blackmore & Jeffrey Y. Sm, 2014. "Rapid seeding of the viral reservoir prior to SIV viraemia in rhesus monkeys," Nature, Nature, vol. 512(7512), pages 74-77, August.
    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. Daniel B. Reeves & Bryan T. Mayer & Allan C. deCamp & Yunda Huang & Bo Zhang & Lindsay N. Carpp & Craig A. Magaret & Michal Juraska & Peter B. Gilbert & David C. Montefiori & Katharine J. Bar & E. Fab, 2023. "High monoclonal neutralization titers reduced breakthrough HIV-1 viral loads in the Antibody Mediated Prevention trials," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. 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.
    3. 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.
    4. Xiaolei Wang & Eunice Vincent & Summer Siddiqui & Katherine Turnbull & Hong Lu & Robert Blair & Xueling Wu & Meagan Watkins & Widade Ziani & Jiasheng Shao & Lara A. Doyle-Meyers & Kasi E. Russell-Lodr, 2022. "Early treatment regimens achieve sustained virologic remission in infant macaques infected with SIV at birth," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    5. Caroline Passaes & Delphine Desjardins & Anaïs Chapel & Valérie Monceaux & Julien Lemaitre & Adeline Mélard & Federico Perdomo-Celis & Cyril Planchais & Maël Gourvès & Nastasia Dimant & Annie David & , 2024. "Early antiretroviral therapy favors post-treatment SIV control associated with the expansion of enhanced memory CD8+ T-cells," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    6. Victoria E. K. Walker-Sperling & Noe B. Mercado & Abishek Chandrashekar & Erica N. Borducchi & Jinyan Liu & Joseph P. Nkolola & Mark Lewis & Jeffrey P. Murry & Yunling Yang & Romas Geleziunas & Merlin, 2022. "Therapeutic efficacy of combined active and passive immunization in ART-suppressed, SHIV-infected rhesus macaques," Nature Communications, Nature, vol. 13(1), pages 1-8, December.
    7. Christoph Kreer & Cosimo Lupo & Meryem S. Ercanoglu & Lutz Gieselmann & Natanael Spisak & Jan Grossbach & Maike Schlotz & Philipp Schommers & Henning Gruell & Leona Dold & Andreas Beyer & Armita Nourm, 2023. "Probabilities of developing HIV-1 bNAb sequence features in uninfected and chronically infected individuals," Nature Communications, Nature, vol. 14(1), pages 1-14, 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:13:y:2022:i:1:d:10.1038_s41467-022-31692-8. 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.