SAMHD1 Restricts HIV-1 Reverse Transcription in Quiescent CD4(+) T-cells

Retrovirology. 2012 Oct 23;9:87. doi: 10.1186/1742-4690-9-87.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / virology*
  • DNA, Viral / metabolism
  • HIV-1 / immunology*
  • HIV-1 / pathogenicity*
  • Host-Pathogen Interactions*
  • Humans
  • Monomeric GTP-Binding Proteins / immunology
  • Monomeric GTP-Binding Proteins / metabolism*
  • Reverse Transcription*
  • SAM Domain and HD Domain-Containing Protein 1
  • Viral Regulatory and Accessory Proteins / immunology
  • Viral Regulatory and Accessory Proteins / metabolism

Substances

  • DNA, Viral
  • Viral Regulatory and Accessory Proteins
  • SAM Domain and HD Domain-Containing Protein 1
  • SAMHD1 protein, human
  • Monomeric GTP-Binding Proteins