title: SAMHD1 restricts HIV-1 reverse transcription in quiescent CD4(+) T-cells.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institut de Génétique Humaine, CNRS UPR1142, Laboratoires de Virologie Moléculaire, Montpellier, France. Benjamin.descours@igh.cnrs.fr
authors.forename: Benjamin
authors.initials: B
authors.lastname: Descours
authors.forename: Alexandra
authors.initials: A
authors.lastname: Cribier
authors.forename: Christine
authors.initials: C
authors.lastname: Chable-Bessia
authors.forename: Diana
authors.initials: D
authors.lastname: Ayinde
authors.forename: Gillian
authors.initials: G
authors.lastname: Rice
authors.forename: Yanick
authors.initials: Y
authors.lastname: Crow
authors.forename: Ahmad
authors.initials: A
authors.lastname: Yatim
authors.forename: Olivier
authors.initials: O
authors.lastname: Schwartz
authors.forename: Nadine
authors.initials: N
authors.lastname: Laguette
authors.forename: Monsef
authors.initials: M
authors.lastname: Benkirane
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D004279:DNA, Viral / Q000378:metabolism; D015497:HIV-1 / Q000276:immunology* / Q000472:pathogenicity*; D054884:Host-Pathogen Interactions; D006801:Humans; D020559:Monomeric GTP-Binding Proteins / Q000276:immunology / Q000378:metabolism*; D048348:Reverse Transcription; D000076106:SAM Domain and HD Domain-Containing Protein 1; D054334:Viral Regulatory and Accessory Proteins / Q000276:immunology / Q000378:metabolism
chemical_list: D004279:DNA, Viral; D054334:Viral Regulatory and Accessory Proteins; D000076106:SAM Domain and HD Domain-Containing Protein 1; C484280:SAMHD1 protein, human; D020559:Monomeric GTP-Binding Proteins