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HIV proviral DNA integration can drive T cell growth ex vivo

  1. Author:
    Yoon, John K [ORCID]
    Holloway, Joseph R
    Wells,Daria [ORCID]
    Kaku, Machika [ORCID]
    Jetton, David
    Brown, Rebecca [ORCID]
    Coffin, John M

  2. Author Address

    Program in Immunology, Graduate School of Biomedical Sciences, Tufts University, Boston, MA 02111., Program in Pharmacology and Experimental Therapeutics, Graduate School of Biomedical Sciences, Tufts University, Boston, MA 02111., Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick, MD 21704., Program in Genetics, Graduate School of Biomedical Sciences, Tufts University, Boston, MA 02111., Program in Immunology, Graduate School of Biomedical Sciences, Tufts University, Boston, MA 02111; john.coffin@tufts.edu., Department of Molecular Biology and Microbiology, Tufts University, Boston, MA 02111.,
    1. Year: 2020
    2. Date: Dec 29
    3. Epub Date: 2020 12 14
  2. Journal: Proceedings of the National Academy of Sciences of the United States of America
    1. 117
    2. 52
    3. Pages: 32880-32882
  4. Type of Article: Article
  5. ISSN: 0027-8424
  1. Abstract:

    In vivo clonal expansion of HIV-infected T cells is an important mechanism of viral persistence. In some cases, clonal expansion is driven by HIV proviral DNA integrated into one of a handful of genes. To investigate this phenomenon in vitro, we infected primary CD4+ T cells with an HIV construct expressing GFP and, after nearly 2 mo of culture and multiple rounds of activation, analyzed the resulting integration site distribution. In each of three replicates from each of two donors, we detected large clusters of integration sites with multiple breakpoints, implying clonal selection. These clusters all mapped to a narrow region within the STAT3 gene. The presence of hybrid transcripts splicing HIV to STAT3 sequences supports a model of LTR-driven STAT3 overexpression as a driver of preferential growth. Thus, HIV integration patterns linked to selective T cell outgrowth can be reproduced in cell culture. The single report of an HIV provirus in a case of AIDS-associated B-cell lymphoma with an HIV provirus in the same part of STAT3 also has implications for HIV-induced malignancy. Copyright © 2020 the Author(s). Published by PNAS.

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External Sources

  1. View Full Text
  2. DOI: 10.1073/pnas.2013194117
  3. PMID: 33318172
  4. PMCID: PMC7777207
  5. View record in Web of Science®
  6. WOS: 000604551600015
  7. PII : 2013194117

Library Notes

  1. Fiscal Year: FY2020-2021
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