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

Autor: Descours Benjamin, Cribier Alexandra, Chable-Bessia Christine, Ayinde Diana, Rice Gillian, Crow Yanick, Yatim Ahmad, Schwartz Olivier, Laguette Nadine, Benkirane Monsef
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Zdroj: Retrovirology, Vol 9, Iss 1, p 87 (2012)
Druh dokumentu: article
ISSN: 1742-4690
DOI: 10.1186/1742-4690-9-87
Popis: 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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