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

Benjamin Descours1*, Alexandra Cribier1, Christine Chable-Bessia1, Diana Ayinde3, Gillian Rice2, Yanick Crow2, Ahmad Yatim1, Olivier Schwartz3, Nadine Laguette1 and Monsef Benkirane1*

Author Affiliations

1 Institut de Génétique Humaine, CNRS UPR1142, Laboratoires de Virologie Moléculaire, Montpellier, France

2 Academic Unit of Medical Genetic, University of Manchester, Manchester, UK

3 Institut Pasteur, Virus and Immunity Unit, URA CNRS 3015, Paris, France

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Retrovirology 2012, 9:87  doi:10.1186/1742-4690-9-87

Published: 23 October 2012

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.

Keywords:
SAMHD1; Quiescent CD4+ T-cell; HIV-1; Reverse transcription; Restriction