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. 2008 Jul 20;377(1):207-15.
doi: 10.1016/j.virol.2008.04.009.

HIV-1 Nef protein expression in human CD34+ progenitors impairs the differentiation of an early T/NK cell precursor

Céline Dorival  1 , Fanny Brizzi, Jean-Daniel Lelièvre, Nathalie Sol-Foulon, Emmanuelle Six, Adeline Henry, Isabelle André-Schmutz, Marina Cavazzana-Calvo, Laure Coulombel, Jérôme Estaquier, Olivier Schwartz, Yves Lévy
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Free article

HIV-1 Nef protein expression in human CD34+ progenitors impairs the differentiation of an early T/NK cell precursor

Céline Dorival et al. Virology. .
Free article

Abstract

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 CD3epsilon(+)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(+) intraCD3epsilon(+) 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.

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