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The largest HIV-1-infected T cell clones in children on long-term combination antiretroviral therapy contain solo LTRs

  1. Author:
    Botha, Johannes C [ORCID]
    Demirov,Dimiter
    Gordijn, Carli
    Katusiime, Mary Grace
    Bale, Michael J
    Wu,Xiaolin
    Wells, Daria
    Hughes,Stephen
    Cotton, Mark F
    Mellors, John W
    Kearney, Mary F
    van Zyl, Gert U
  2. Author Address

    Stellenbosch University , Cape Town, South Africa., Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research , Frederick, Maryland, USA., HIV Dynamics and Replication Program, National Cancer Institute , Frederick, Maryland, USA., Laboratory of Epigenetics and Immunity, Department of Pathology and Laboratory Medicine, Weill Cornell Medicine , New York, New York, USA., Division of Infectious Diseases, Department of Medicine, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania, USA.,
    1. Year: 2023
    2. Date: Aug 02
    3. Epub Date: 2023 08 02
  1. Journal: mBio
    1. Pages: e0111623
  2. Type of Article: Article
  3. Article Number: e0111623
  1. Abstract:

    Combination antiretroviral therapy (cART) suppresses viral replication but does not cure HIV infection because a reservoir of infectious (intact) HIV proviruses persists in long-lived CD4+T cells. However, a large majority (>95%) of HIV-infected cells that persist on effective cART carry defective (non-infectious) proviruses. Defective proviruses consisting of only a single LTR (solo long terminal repeat) are commonly found as endogenous retroviruses in many animal species, but the frequency of solo-LTR HIV proviruses has not been well defined. Here we show that, in five pediatric donors whose viremia was suppressed on cART for at least 5 years, the proviruses in the nine largest clones of HIV-infected cells were solo LTRs. The sizes of five of these clones were assayed longitudinally by integration site-specific quantitative PCR. Minor waxing and waning of the clones was observed, suggesting that these clones are generally stable over time. Our findings show that solo LTRs comprise a large fraction of the proviruses in infected cell clones that persist in children on long-term cART. IMPORTANCE This work highlights that severely deleted HIV-1 proviruses comprise a significant proportion of the proviral landscape and are often overlooked.

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External Sources

  1. DOI: 10.1128/mbio.01116-23
  2. PMID: 37530525

Library Notes

  1. Fiscal Year: FY2022-2023
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