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

Benjamin Descours (1) , Alexandra Cribier (1) , Christine Chable-Bessia (1) , Diana Ayinde (2) , Gillian Rice (3) , Yanick Crow (3) , Ahmad Yatim (1) , Olivier Schwartz (2) , Nadine Laguette (1) , Monsef Benkirane (1)

1 IGH - Institut de génétique humaine
2 Virus et Immunité
3 Academic Unit of Medical Genetic

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, Restriction, Reverse transcription

Domains: Life Sciences [q-bio]; Human health and pathology; Infectious diseases

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⟩