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

Sci Transl Med. 2020 Jan 29;12(528):eaax6795. doi: 10.1126/scitranslmed.aax6795.


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.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Differentiation / genetics
  • Cell Proliferation / drug effects
  • DNA, Viral / blood
  • DNA, Viral / genetics
  • Gene Expression Regulation, Viral
  • HIV-1 / genetics
  • HIV-1 / growth & development
  • HIV-1 / immunology*
  • Humans
  • Immunologic Memory*
  • Lymphocyte Activation / immunology
  • Lymphocyte Count
  • Phenotype
  • Phylogeny
  • Proviruses / immunology*
  • T-Lymphocyte Subsets / immunology*
  • Transcription, Genetic
  • Virus Replication / genetics


  • DNA, Viral