%0 Journal Article %T HIV-1 Nef protein expression in human CD34(+) progenitors impairs the differentiation of an early T/NK cell precursor. %+ Faculté de médecine %+ Service d'immunologie clinique [Créteil] %+ Virus et Immunité %+ Developpement Normal et Pathologique du Système Immunitaire %+ Microenvironnement et Physiopathologie de la Differenciation %A Dorival, Céline %A Brizzi, Fanny %A Lelièvre, Jean-Daniel %A Sol-Foulon, Nathalie %A Six, Emmanuelle %A Henry, Adeline %A André-Schmutz, Isabelle %A Cavazzana-Calvo, Marina %A Coulombel, Laure %A Estaquier, Jérôme %A Schwartz, Olivier %A Lévy, Yves %< avec comité de lecture %@ 0042-6822 %J Virology %I Elsevier %V 377 %N 1 %P 207-15 %8 2008-07-20 %D 2008 %R 10.1016/j.virol.2008.04.009 %M 18555888 %Z Life Sciences [q-bio]/ImmunologyJournal articles %X HIV-1 impairs the production of T cells, through mechanisms that are still unknown. Here, we investigated the effect of the expression of HIV-1 Nef on the T-cell potential of human hematopoietic CD34(+) precursors. Those progenitors were transduced by using lentiviral vectors expressing Nef and cultured on OP9-DL1 cells allowing the differentiation of T cell from human hematopoietic precursors. We demonstrate that Nef impairs the generation of a CD3varepsilon(+)CD5(+) CD1a(+) precursor stage that has initiated a D-J rearrangement of the TCRbeta locus. Onward stages of T-cell development were also affected with a quantitative reduction of CD4(+) intraCD3varepsilon(+) Immature single positive cells (ISP), Double Positive (DP) CD4(+)CD8(+) TCRalphabeta T cells and CD56(+) NK cells. But B cell production was not affected. Limiting dilution analyses demonstrated a significant reduction in the frequency of T/NK progenitors among Nef-expressing CD34(+) cells. Altogether, these data demonstrate that Nef interferes with the differentiation of a primitive lymphoid human precursor with a T/NK potential. %G English %L pasteur-00293159 %U https://pasteur.hal.science/pasteur-00293159 %~ PASTEUR %~ UNIV-PARIS5 %~ CNRS %~ UNIV-PSUD %~ APHP %~ RIIP_PARIS %~ UPEC %~ UNIV-PARIS-SACLAY %~ UNIV-PSUD-SACLAY %~ UNIV-PARIS