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. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
|