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Retrovirology. 2012 Oct 23;9:87. doi: 10.1186/1742-4690-9-87.

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

Author information

1
Institut de Génétique Humaine, CNRS UPR1142, Laboratoires de Virologie Moléculaire, Montpellier, France. Benjamin.descours@igh.cnrs.fr

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.

PMID:
23092122
PMCID:
PMC3494655
DOI:
10.1186/1742-4690-9-87
[Indexed for MEDLINE]
Free PMC Article

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