title: SAMHD1 is the dendritic- and myeloid-cell-specific HIV-1 restriction factor counteracted by Vpx.
abstract: The primate lentivirus auxiliary protein Vpx counteracts an unknown restriction factor that renders human dendritic and myeloid cells largely refractory to HIV-1 infection. Here we identify SAMHD1 as this restriction factor. SAMHD1 is a protein involved in Aicardi-Goutières syndrome, a genetic encephalopathy with symptoms mimicking congenital viral infection, that has been proposed to act as a negative regulator of the interferon response. We show that Vpx induces proteasomal degradation of SAMHD1. Silencing of SAMHD1 in non-permissive cell lines alleviates HIV-1 restriction and is associated with a significant accumulation of viral DNA in infected cells. Concurrently, overexpression of SAMHD1 in sensitive cells inhibits HIV-1 infection. The putative phosphohydrolase activity of SAMHD1 is probably required for HIV-1 restriction. Vpx-mediated relief of restriction is abolished in SAMHD1-negative cells. Finally, silencing of SAMHD1 markedly increases the susceptibility of monocytic-derived dendritic cells to infection. Our results demonstrate that SAMHD1 is an antiretroviral protein expressed in cells of the myeloid lineage that inhibits an early step of the viral life cycle.
authors: Institut de Génétique Humaine, Laboratoire de Virologie Moléculaire, CNRS UPR1142, Montpellier 34000, France. nadine.laguette@igh.cnrs.fr
authors: Nadine
authors: N
authors: Laguette
authors: Bijan
authors: B
authors: Sobhian
authors: Nicoletta
authors: N
authors: Casartelli
authors: Mathieu
authors: M
authors: Ringeard
authors: Christine
authors: C
authors: Chable-Bessia
authors: Emmanuel
authors: E
authors: Ségéral
authors: Ahmad
authors: A
authors: Yatim
authors: Stéphane
authors: S
authors: Emiliani
authors: Olivier
authors: O
authors: Schwartz
authors: Monsef
authors: M
authors: Benkirane
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