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

Descours, Benjamin; Cribier, Alexandra; Chable-Bessia, Christine; Ayinde, Diana; Rice, Gillian; Crow, Yanick; Yatim, Ahmad; Schwartz, Olivier; Laguette, Nadine; Benkirane, Monsef

Retrovirology. 2012;9:87.

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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.

Bibliographic metadata

Type of resource:
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Publication type:
Published date:
Journal title:
Abbreviated journal title:
ISSN:
Place of publication:
England
Volume:
9
Pagination:
87
Digital Object Identifier:
10.1186/1742-4690-9-87
Pubmed Identifier:
23092122
Pii Identifier:
1742-4690-9-87
Access state:
Active

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Record metadata

Manchester eScholar ID:
uk-ac-man-scw:203138
Created by:
Crow, Yanick
Created:
30th July, 2013, 13:16:51
Last modified by:
Crow, Yanick
Last modified:
30th July, 2013, 13:16:51

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