The HIV-1 Nef protein has a dual role in T cell receptor signaling in infected CD4+ T lymphocytes

Virology. 2011 Feb 20;410(2):316-26. doi: 10.1016/j.virol.2010.11.018. Epub 2010 Dec 21.

Abstract

The phenotypic changes that are induced by immune activation in CD4(+) T lymphocytes provide an optimal environment for efficient HIV-1 replication in these cells. The pathogenic Nef protein of HIV-1 modulates the T cell receptor (TCR) signaling, but whether this has a positive or negative effect on cellular activation is a matter of debate. Here we have investigated the response to TCR stimulation of primary CD4(+) T lymphocytes infected with wt or Nef-deficient HIV-1. Results show that, in freshly isolated quiescent T cells, Nef superinduces NFAT and IL-2 production bypassing early TCR effector molecules. Conversely, the early phosphorylation of PLC-γ1, the induction of NFAT, and the expression of IL-2 are impaired by Nef in sub-optimally activated/resting T cells. Our data indicate that Nef has a dual role in the modulation of TCR signaling aimed at favoring HIV-1 replication and spread in both quiescent and metabolically active CD4(+) T lymphocytes.

MeSH terms

  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / virology*
  • HIV-1 / genetics
  • HIV-1 / pathogenicity*
  • Interleukin-2 / biosynthesis
  • Lymphocyte Activation
  • NFATC Transcription Factors / biosynthesis
  • Receptors, Antigen, T-Cell / metabolism*
  • nef Gene Products, Human Immunodeficiency Virus / deficiency
  • nef Gene Products, Human Immunodeficiency Virus / metabolism*

Substances

  • Interleukin-2
  • NFATC Transcription Factors
  • Receptors, Antigen, T-Cell
  • nef Gene Products, Human Immunodeficiency Virus
  • nef protein, Human immunodeficiency virus 1