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Contribution of intact viral genomes persisting in blood and tissues during ART to plasma viral rebound in SHIV-infected rhesus macaques

  1. Author:
    Trifone, César
    Richard, Corentin
    Pagliuzza, Amélie
    Dufour, Caroline
    Lemieux, Audrée
    Clark, Natasha M
    Janaka, Sanath K
    Fennessey,Christine
    Keele,Brandon
    Fromentin, Rémi
    Estes, Jacob D
    Kaufmann, Daniel E
    Finzi, Andrés
    Evans, David T
    Chomont, Nicolas

  2. Author Address

    1Centre de Recherche du CHUM, Montréal, QC H2X 0A9, Canada. 2Département de Microbiologie, infectiologie et immunologie, Faculté de Médecine, Université de Montréal, Montréal, QC H3T 1J4, Canada. 3University College of London, London, England WC1E 6BT, UK. 4Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53707, USA. 5AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21701, USA. 6Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR 97239, USA. 7Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97239, USA. 8Département de Médecine, Université de Montréal, Montréal, QC H3T 1J4, Canada. 9Division of Infectious Diseases, Department of Medicine, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland.
    1. Year: 2025
    2. Date: Mar 21
    3. Epub Date: 2025 02 11
  2. Journal: iScience
    1. 28
    2. 3
    3. Pages: 111998
  4. Type of Article: Article
  5. Article Number: 111998
  1. Abstract:

    Persistent SIV/HIV reservoirs are the primary obstacle to a cure and the source of viral rebound after ART interruption (ATI). However, the anatomical source of viral rebound remains elusive. Here, we characterized the proviral landscape in the blood, inguinal, and axillary lymph nodes and colon biopsies of five SHIV-infected rhesus macaques (RMs), under ART for 28 weeks. From the 144 near full-length (NFL) proviral sequences obtained pre-ATI, 35% were genetically intact and only 2.8% were found in multiple copies. Envelope sequences of plasma rebounding viruses after ATI, more frequently matched pre-ATI intact proviruses retrieved from lymph nodes compared to sequences isolated from the blood or the colon (4, 1, and 1 pair of matched sequences, respectively). Our results suggest that clonal expansion of infected cells rare in this model, and that intact proviruses persisting in the lymph nodes may be a preferential source of viral rebound upon ATI. © 2025 The Author(s).

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External Sources

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  2. DOI: 10.1016/j.isci.2025.111998
  3. PMID: 40104070
  4. PMCID: PMC11914814
  5. PII : S2589-0042(25)00258-5

Library Notes

  1. Fiscal Year: FY2024-2025
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