Clonally Expanded CD4+ T Cells Can Produce Infectious HIV-1 in Vivo

Proc Natl Acad Sci U S A. 2016 Feb 16;113(7):1883-8. doi: 10.1073/pnas.1522675113. Epub 2016 Feb 8.

Abstract

Reservoirs of infectious HIV-1 persist despite years of combination antiretroviral therapy and make curing HIV-1 infections a major challenge. Most of the proviral DNA resides in CD4(+)T cells. Some of these CD4(+)T cells are clonally expanded; most of the proviruses are defective. It is not known if any of the clonally expanded cells carry replication-competent proviruses. We report that a highly expanded CD4(+) T-cell clone contains an intact provirus. The highly expanded clone produced infectious virus that was detected as persistent plasma viremia during cART in an HIV-1-infected patient who had squamous cell cancer. Cells containing the intact provirus were widely distributed and significantly enriched in cancer metastases. These results show that clonally expanded CD4(+)T cells can be a reservoir of infectious HIV-1.

Keywords: HIV persistence; clonal expansion of infected cells; replication-competent HIV.

Publication types

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

MeSH terms

  • Anti-HIV Agents / therapeutic use
  • CD4-Positive T-Lymphocytes / virology*
  • HIV Infections / blood
  • HIV Infections / drug therapy
  • HIV Infections / virology
  • HIV-1 / pathogenicity
  • HIV-1 / physiology*
  • Humans
  • Molecular Sequence Data
  • Virulence
  • Virus Replication*

Substances

  • Anti-HIV Agents

Associated data

  • GENBANK/KU641402
  • GENBANK/KU644730
  • GENBANK/KU645194