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

Francesca Neri, Giorgia Giolo, Marina Potestà, Stefania Petrini, Margherita Doria

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)316-326
Number of pages11
Issue number2
Publication statusPublished - Feb 20 2011


  • CD4 T lymphocytes
  • HIV-1
  • IL-2
  • Nef
  • NFAT
  • T cell activation
  • TCR

ASJC Scopus subject areas

  • Virology

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