Different human resting memory CD4 + T cell subsets show similar low inducibility of latent HIV-1 proviruses.

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  • Additional Information
    • Source:
      Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 101505086 Publication Model: Print Cited Medium: Internet ISSN: 1946-6242 (Electronic) Linking ISSN: 19466234 NLM ISO Abbreviation: Sci Transl Med Subsets: MEDLINE
    • Publication Information:
      Original Publication: Washington, DC : American Association for the Advancement of Science
    • Subject Terms:
      Immunologic Memory*; CD4-Positive T-Lymphocytes/*immunology ; HIV-1/*immunology ; Proviruses/*immunology ; T-Lymphocyte Subsets/*immunology; Adult ; Cell Differentiation/genetics ; Cell Proliferation/drug effects ; DNA, Viral/blood ; DNA, Viral/genetics ; Gene Expression Regulation, Viral ; HIV-1/genetics ; HIV-1/growth & development ; Humans ; Lymphocyte Activation/immunology ; Lymphocyte Count ; Phenotype ; Phylogeny ; Transcription, Genetic ; Virus Replication/genetics
    • Abstract:
      The latent reservoir of HIV-1 in resting CD4 + T cells is a major barrier to cure. It is unclear whether the latent reservoir resides principally in particular subsets of CD4 + T cells, a finding that would have implications for understanding its stability and developing curative therapies. Recent work has shown that proliferation of HIV-1-infected CD4 + T cells is a major factor in the generation and persistence of the latent reservoir and that latently infected T cells that have clonally expanded in vivo can proliferate in vitro without producing virions. In certain CD4 + memory T cell subsets, the provirus may be in a deeper state of latency, allowing the cell to proliferate without producing viral proteins, thus permitting escape from immune clearance. To evaluate this possibility, we used a multiple stimulation viral outgrowth assay to culture resting naïve, central memory (TCM), transitional memory (TTM), and effector memory (TEM) CD4 + T cells from 10 HIV-1-infected individuals on antiretroviral therapy. On average, only 1.7% of intact proviruses across all T cell subsets were induced to transcribe viral genes and release replication-competent virus after stimulation of the cells. We found no consistent enrichment of intact or inducible proviruses in any T cell subset. Furthermore, we observed notable plasticity among the canonical memory T cell subsets after activation in vitro and saw substantial person-to-person variability in the inducibility of infectious virus release. This finding complicates the vision for a targeted approach for HIV-1 cure based on T cell memory subsets.
      (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
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    • Grant Information:
      UM1 AI126620 United States AI NIAID NIH HHS; P30 AI094189 United States AI NIAID NIH HHS; UM1 AI126603 United States AI NIAID NIH HHS; UM1 AI126611 United States AI NIAID NIH HHS; P30 AI027763 United States AI NIAID NIH HHS
    • Accession Number:
      0 (DNA, Viral)
    • Publication Date:
      Date Created: 20200131 Date Completed: 20200925 Latest Revision: 20240330
    • Publication Date:
      20250114
    • Accession Number:
      PMC7875249
    • Accession Number:
      10.1126/scitranslmed.aax6795
    • Accession Number:
      31996465