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

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 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.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-00293159
Contributor : Mireille Gau <>
Submitted on : Thursday, July 3, 2008 - 5:03:08 PM
Last modification on : Wednesday, September 16, 2020 - 4:54:37 PM

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Céline Dorival, Fanny Brizzi, Jean-Daniel Lelièvre, Nathalie Sol-Foulon, Emmanuelle Six, et al.. HIV-1 Nef protein expression in human CD34(+) progenitors impairs the differentiation of an early T/NK cell precursor.. Virology, Elsevier, 2008, 377 (1), pp.207-15. ⟨10.1016/j.virol.2008.04.009⟩. ⟨pasteur-00293159⟩

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