SAMHD1 restricts HIV-1 reverse transcription in quiescent CD4+ T-cells. - Institut Pasteur Access content directly
Journal Articles Retrovirology Year : 2012

SAMHD1 restricts HIV-1 reverse transcription in quiescent CD4+ T-cells.

Alexandra Cribier
  • Function : Author
  • PersonId : 932506
Christine Chable-Bessia
  • Function : Author
  • PersonId : 932507
Diana Ayinde
  • Function : Author
  • PersonId : 932508
Gillian Rice
  • Function : Author
  • PersonId : 932509
Yanick Crow
Ahmad Yatim
  • Function : Author
  • PersonId : 932510
Olivier Schwartz
Nadine Laguette

Abstract

ABSTRACT: BACKGROUND: Quiescent CD4+ T lymphocytes are highly refractory to HIV-1 infection due to a block at reverse transcription. RESULTS: Examination of SAMHD1 expression in peripheral blood lymphocytes shows that SAMHD1 is expressed in both CD4+ and CD8+ T cells at levels comparable to those found in myeloid cells. Treatment of CD4+ T cells with Virus-Like Particles (VLP) containing Vpx results in the loss of SAMHD1 expression that correlates with an increased permissiveness to HIV-1 infection and accumulation of reverse transcribed viral DNA without promoting transcription from the viral LTR. Importantly, CD4+ T-cells from patients with Aicardi-Goutières Syndrome harboring mutation in the SAMHD1 gene display an increased susceptibility to HIV-1 infection that is not further enhanced by VLP-Vpx-treatment. CONCLUSION: Here, we identified SAMHD1 as the restriction factor preventing efficient viral DNA synthesis in non-cycling resting CD4+ T-cells. These results highlight the crucial role of SAMHD1 in mediating restriction of HIV-1 infection in quiescent CD4+ T-cells and could impact our understanding of HIV-1 mediated CD4+ T-cell depletion and establishment of the viral reservoir, two of the HIV/AIDS hallmarks.
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Dates and versions

pasteur-00750469 , version 1 (10-11-2012)

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Benjamin Descours, Alexandra Cribier, Christine Chable-Bessia, Diana Ayinde, Gillian Rice, et al.. SAMHD1 restricts HIV-1 reverse transcription in quiescent CD4+ T-cells.. Retrovirology, 2012, 9 (1), pp.87. ⟨10.1186/1742-4690-9-87⟩. ⟨pasteur-00750469⟩
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