SAMHD1 Restricts HIV-1 Cell-to-Cell Transmission And Limits Immune Detection In Monocyte-Derived Dendritic Cells.

Institut Pasteur, Unité Virus et Immunité, Département de Virologie, and CNRS, URA3015, 28 rue du Docteur Roux, F-75015, Paris, France.
Journal of Virology (Impact Factor: 4.65). 12/2012; DOI: 10.1128/JVI.02514-12
Source: PubMed

ABSTRACT SAMHD1 is a viral restriction factor expressed in dendritic cells and other cells, inhibiting infection by cell-free HIV-1 particles. SAMHD1 depletes the intracellular pool of dNTPs, thus impairing HIV-1 reverse transcription and productive infection in non-cycling cells. The Vpx protein from HIV-2 or SIVsm/SIVmac antagonizes the effect of SAMHD1 by triggering its degradation. A large part of HIV-1 spread occurs through direct contacts between infected cells and bystander target cells. Here, we asked whether SAMHD1 impairs direct HIV-1 transmission from infected T lymphocytes to monocyte-derived dendritic cells (MDDC). HIV-1-infected lymphocytes were cocultivated with MDDC that have been pre-treated or not with Vpx, or with siRNA against SAMHD1. We show that in the cocultures, SAMHD1 significantly inhibits productive cell-to-cell transmission to target MDDC and prevents type-I IFN response and expression of the interferon-stimulated gene MxA. Therefore, SAMHD1, by controlling the sensitivity of MDDC to HIV-1 infection during intercellular contacts, impacts their ability to sense the virus and to trigger an innate immune response.

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