HIV infection of primary human T cells is determined by tunable thresholds of T cell activation

Eur J Immunol. 2004 Jun;34(6):1705-14. doi: 10.1002/eji.200424892.


HIV infection of primary human T cells requires T cell activation signals. However, how strength, duration, and quality of TCR signals affect susceptibility of resting human T cells to HIV infection remains poorly understood. We found that the same threshold and duration of antigen signals that lead to optimal T cell activation are required for HIV to progress beyond the level of reverse transcription within resting T cells. Remarkably, sustained cytokine signaling from the IL-2 receptor following TCR triggering was critical in establishing productive infection. While blockade of TCR signaling pathways with inhibitors of the phosphatidylinositol 3-kinase pathway caused a partial pre-integration block, another inhibitor, rapamycin, completely suppressed the infection. In contrast, cyclosporin A or FK506, inhibitors of NFAT, failed to block infection if the T cells were pre-activated. Collectively, these results bring to light significant parallels between successful HIV infection and optimal thresholds of T cell activation. Furthermore, our results underscore the critical role of IL-2 signaling in establishing productive HIV infection. These findings have important implications for our understanding of the complex interplay of HIV with host factors induced upon T cell activation.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / virology*
  • Cell Division / immunology
  • Cyclosporine / pharmacology
  • DNA-Binding Proteins / immunology
  • HIV / immunology*
  • HIV Infections / immunology*
  • Humans
  • Kinetics
  • Lymphocyte Activation / immunology
  • NFATC Transcription Factors
  • Nuclear Proteins*
  • RNA-Directed DNA Polymerase / immunology
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Interleukin-2 / immunology
  • Reverse Transcriptase Inhibitors / pharmacology
  • Signal Transduction / immunology
  • Sirolimus / pharmacology
  • Tacrolimus / pharmacology
  • Transcription Factors / immunology
  • Virus Replication / immunology


  • DNA-Binding Proteins
  • NFATC Transcription Factors
  • Nuclear Proteins
  • Receptors, Antigen, T-Cell
  • Receptors, Interleukin-2
  • Reverse Transcriptase Inhibitors
  • Transcription Factors
  • Cyclosporine
  • RNA-Directed DNA Polymerase
  • Sirolimus
  • Tacrolimus