title: The HIV-1 Nef protein has a dual role in T cell receptor signaling in infected CD4+ T lymphocytes.
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.
authors.affiliation: Laboratory of Immunoinfectivology, Children's Hospital Bambino Gesù, 00165 Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Neri
authors.forename: Giorgia
authors.initials: G
authors.lastname: Giolo
authors.forename: Marina
authors.initials: M
authors.lastname: Potestà
authors.forename: Stefania
authors.initials: S
authors.lastname: Petrini
authors.forename: Margherita
authors.initials: M
authors.lastname: Doria
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity*; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D050778:NFATC Transcription Factors / Q000096:biosynthesis; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000172:deficiency / Q000378:metabolism*
chemical_list: D007376:Interleukin-2; D050778:NFATC Transcription Factors; D011948:Receptors, Antigen, T-Cell; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1