CD32a is a marker of a CD4 T-cell HIV reservoir harbouring replication-competent proviruses

Nature. 2017 Mar 23;543(7646):564-567. doi: 10.1038/nature21710. Epub 2017 Mar 15.

Abstract

The persistence of the HIV reservoir in infected individuals is a major obstacle to the development of a cure for HIV. Here, using an in vitro model of HIV-infected quiescent CD4 T cells, we reveal a gene expression signature of 103 upregulated genes that are specific for latently infected cells, including genes for 16 transmembrane proteins. In vitro screening for surface expression in HIV-infected quiescent CD4 T cells shows that the low-affinity receptor for the immunoglobulin G Fc fragment, CD32a, is the most highly induced, with no detectable expression in bystander cells. Notably, productive HIV-1 infection of T-cell-receptor-stimulated CD4 T cells is not associated with CD32a expression, suggesting that a quiescence-dependent mechanism is required for its induction. Using blood samples from HIV-1-positive participants receiving suppressive antiretroviral therapy, we identify a subpopulation of 0.012% of CD4 T cells that express CD32a and host up to three copies of HIV DNA per cell. This CD32a+ reservoir was highly enriched in inducible replication-competent proviruses and can be predominant in some participants. Our discovery that CD32a+ lymphocytes represent the elusive HIV-1 reservoir may lead to insights that will facilitate the specific targeting and elimination of this reservoir.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / therapeutic use
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / metabolism*
  • CD4-Positive T-Lymphocytes / virology*
  • Cell Division
  • Cell Separation
  • Cells, Cultured
  • DNA, Viral / analysis
  • Gene Expression Profiling
  • HEK293 Cells
  • HIV Infections / blood
  • HIV Infections / drug therapy
  • HIV Infections / immunology
  • HIV Infections / virology*
  • HIV-1 / genetics
  • HIV-1 / growth & development*
  • HIV-1 / isolation & purification
  • Humans
  • Proviruses / genetics
  • Proviruses / growth & development*
  • Proviruses / isolation & purification
  • Receptors, IgG / metabolism*
  • Up-Regulation / genetics
  • Virus Latency / drug effects
  • Virus Latency / genetics
  • Virus Latency / immunology
  • Virus Replication*

Substances

  • Anti-HIV Agents
  • DNA, Viral
  • Fc gamma receptor IIA
  • Receptors, IgG