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Early Emergence and Long-Term Persistence of HIV-Infected T-Cell Clones in Children

  1. Author:
    Bale, Michael J.
    Katusiime, Mary Grace
    Wells, Daria
    Wu, Xiaolin
    Spindler, Jonathan
    Halvas, Elias K.
    Cyktor, Joshua C.
    Wiegand, Ann
    Shao, Wei
    Cotton, Mark F.
    Hughes, Stephen H.
    Mellors, John W.
    Coffin, John M.
    Van Zyl, Gert U.
    Kearney, Mary F.

  2. Author Address

    NCI, HIV Dynam & Replicat Program, CCR, Frederick, MD 21701 USA.Frederick Natl Lab Canc Res, Leidos Biomed Res Inc, Frederick, MD USA.Univ Pittsburgh, Dept Med, Pittsburgh, PA USA.Stellenbosch Univ, Tygerberg Childrens Hosp, Dept Pediat & Child Hlth, Cape Town, South Africa.Stellenbosch Univ, Family Ctr Res Ubuntu, Cape Town, South Africa.Tufts Univ, Dept Mol Biol & Microbiol, Boston, MA 02111 USA.Stellenbosch Univ, Div Med Virol, Cape Town, South Africa.Natl Hlth Lab Serv Tygerberg, Cape Town, South Africa.Weill Cornell Med Coll, New York, NY USA.
    1. Year: 2021
    2. Date: Apr 8
  2. Journal: mBio
  3. Amer Soc Microbiology
    1. 12
    2. 2
  5. Type of Article: Article
  6. Article Number: ARTN e00568-21
  7. ISSN: 2150-7511
  1. Abstract:

    Little is known about the emergence and persistence of human immunodeficiency virus (HIV)-infected T-cell clones in perinatally infected children. We analyzed peripheral blood mononuclear cells (PBMCs) for clonal expansion in 11 children who initiated antiretroviral therapy (ART) between 1.8 and 17.4months of age and with viremia suppressed for 6 to 9 years. We obtained 8,662 HIV type 1 (HIV-1) integration sites from pre-ART samples and 1,861 sites from on-ART samples. Expanded clones of infected cells were detected pre-ART in 10/11 children. In 8 children, infected cell clones detected pre-ART persisted for 6 to 9 years on ART. A comparison of integration sites in the samples obtained on ART with healthy donor PBMCs infected ex vivo showed selection for cells with proviruses integrated in BACH2 and STAT5B. Our analyses indicate that, despite marked differences in T-cell composition and dynamics between children and adults, HIV-infected cell clones are established early in children, persist for up to 9 years on ART, and can be driven by proviral integration in proto-oncogenes.

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External Sources

  1. View Full Text
  2. DOI: 10.1128/mBio.00568-21
  3. PMID: 33832973
  4. PMCID: PMC8092253
  5. View record in Web of Science®
  6. WOS: 000643734400005

Library Notes

  1. Open Access Publication
  2. Fiscal Year: FY2020-2021
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