Effector memory differentiation increases detection of replication-competent HIV-l in resting CD4+ T cells from virally suppressed individuals

PLoS Pathog. 2019 Oct 14;15(10):e1008074. doi: 10.1371/journal.ppat.1008074. eCollection 2019 Oct.


Studies have demonstrated that intensive ART alone is not capable of eradicating HIV-1, as the virus rebounds within a few weeks upon treatment interruption. Viral rebound may be induced from several cellular subsets; however, the majority of proviral DNA has been found in antigen experienced resting CD4+ T cells. To achieve a cure for HIV-1, eradication strategies depend upon both understanding mechanisms that drive HIV-1 persistence as well as sensitive assays to measure the frequency of infected cells after therapeutic interventions. Assays such as the quantitative viral outgrowth assay (QVOA) measure HIV-1 persistence during ART by ex vivo activation of resting CD4+ T cells to induce latency reversal; however, recent studies have shown that only a fraction of replication-competent viruses are inducible by primary mitogen stimulation. Previous studies have shown a correlation between the acquisition of effector memory phenotype and HIV-1 latency reversal in quiescent CD4+ T cell subsets that harbor the reservoir. Here, we apply our mechanistic understanding that differentiation into effector memory CD4+ T cells more effectively promotes HIV-1 latency reversal to significantly improve proviral measurements in the QVOA, termed differentiation QVOA (dQVOA), which reveals a significantly higher frequency of the inducible HIV-1 replication-competent reservoir in resting CD4+ T cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anti-Retroviral Agents / therapeutic use
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / virology*
  • Cell Differentiation
  • Cell Proliferation
  • Cells, Cultured
  • HIV Infections / immunology
  • HIV-1 / growth & development
  • HIV-1 / immunology*
  • HIV-1 / physiology*
  • Humans
  • Immunologic Memory / immunology*
  • Male
  • Middle Aged
  • Proviruses / growth & development
  • Viral Load / drug effects
  • Virus Latency / drug effects
  • Virus Latency / immunology*
  • Virus Replication / drug effects


  • Anti-Retroviral Agents