SAMHD1: a new insight into HIV-1 restriction in myeloid cells

Corine St Gelais,Li Wu

doi:10.1186/1742-4690-8-55

Abstract

Human myeloid-lineage cells are refractory to HIV-1 infection. The Vpx proteins from HIV-2 and sooty mangabey SIV render these cells permissive to HIV-1 infection through proteasomal degradation of a putative restriction factor. Two recent studies discovered the cellular protein SAMHD1 to be this restriction factor, demonstrating that Vpx induces proteasomal degradation of SAMHD1 and enhances HIV-1 infection in myeloid-lineage cells. SAMHD1 functions as a myeloid-cell-specific HIV-1 restriction factor by inhibiting viral DNA synthesis. Here we discuss the implications of these findings in delineating the mechanisms of HIV-1 restriction in myeloid-lineage cells and the potential role of Vpx in lentiviral pathogenesis.

Highlights

Myeloid-lineage cells, including monocytes, dendritic cells (DCs) and macrophages, play a multifaceted role in HIV-1 initial infection and viral dissemination; these cell types are restrictive to post-entry HIV-1 infection in vitro [1,2]
Hrecka and colleagues identified SAMHD1 from HEK 293T cells expressing tagged Vpx in a proteomic screen using multidimensional protein identification technology [10]. They demonstrated that Vpx relieves the inhibition of HIV-1 infection in monocyte-derived macrophages by mediating proteasomedependent degradation of SAMHD1 through the CUL4A/DCAF1 E3 ubiquitin ligase [10]
Laguette et al showed that over-expression of a HD domain mutant SAMHD1 in U937 cells fails to restrict HIV-1, suggesting that the phosphodiesterase activity of the HD domain is important for the restriction function of SAMHD1

Summary

Introduction

Myeloid-lineage cells, including monocytes, dendritic cells (DCs) and macrophages, play a multifaceted role in HIV-1 initial infection and viral dissemination; these cell types are restrictive to post-entry HIV-1 infection in vitro [1,2]. New findings and discussion Using mass spectrometry, Laguette et al identified SAMHD1 as a novel Vpx-interacting protein purified from differentiated human monocytic THP-1 cells that express tagged Vpx [9]. They demonstrated that Vpx relieves the inhibition of HIV-1 infection in monocyte-derived macrophages by mediating proteasomedependent degradation of SAMHD1 through the CUL4A/DCAF1 E3 ubiquitin ligase [10].

Results

Conclusion