Induction of HIV-1 latency and reactivation in primary memory CD4+ T cells

Blood. 2009 Jan 1;113(1):58-65. doi: 10.1182/blood-2008-07-168393. Epub 2008 Oct 10.

Abstract

The use of antiretroviral therapy in HIV type 1 (HIV-1)-infected patients does not lead to virus eradication. This is due, to a significant degree, to the fact that HIV-1 can establish a highly stable reservoir of latently infected cells. In this work, we describe an ex vivo experimental system that generates high levels of HIV-1 latently infected memory cells using primary CD4+ T cells. Using this model, we were able to dissect the T cell-signaling pathways and to characterize the long terminal repeat (LTR) cis-acting elements involved in reactivation of HIV-1 in memory CD4+ T cells. We conclude that Lck and nuclear factor of activated T cells (NFAT), but not NF-kappaB, are required for optimal latent virus reactivation in memory T cells. We also found that the cis-acting elements which are critical toward HIV-1 reactivation are the Sp1 and kappaB/NFAT transcription factor binding sites.

Publication types

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

MeSH terms

  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / virology*
  • Cell Line
  • Genetic Complementation Test
  • HIV Infections / immunology
  • HIV Infections / virology*
  • HIV-1 / genetics
  • HIV-1 / growth & development*
  • Humans
  • Immunologic Memory / immunology*
  • Kidney / cytology
  • Mutagenesis
  • NF-kappa B / metabolism
  • NFATC Transcription Factors / metabolism
  • Signal Transduction / immunology
  • Sp1 Transcription Factor / metabolism
  • Terminal Repeat Sequences / genetics
  • Virus Latency / genetics
  • Virus Latency / immunology
  • Virus Replication / genetics
  • Virus Replication / immunology

Substances

  • NF-kappa B
  • NFATC Transcription Factors
  • Sp1 Transcription Factor