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

Retrovirology

Monsef Benkirane²  Nadine Laguette²  Olivier Schwartz¹  Ahmad Yatim²  Yanick Crow³  Gillian Rice³  Diana Ayinde¹  Christine Chable-Bessia²  Alexandra Cribier²  Benjamin Descours² 

[1] Institut Pasteur, Virus and Immunity Unit, URA CNRS 3015, Paris, France;Institut de Génétique Humaine, CNRS UPR1142, Laboratoires de Virologie Moléculaire, Montpellier, France;Academic Unit of Medical Genetic, University of Manchester, Manchester, UK

关键词: Restriction;    Reverse transcription;    HIV-1;    Quiescent CD4⁺ T-cell;    SAMHD1;   

Others  :  1209255
DOI  :  10.1186/1742-4690-9-87

 received in 2012-10-05, accepted in 2012-10-16,  发布年份 2012

【 摘 要 】

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.

【 授权许可】

   
2012 Descours et al.; licensee BioMed Central Ltd.

【 图 表 】

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