title: SAMHD1 restricts HIV-1 cell-to-cell transmission and limits immune detection in monocyte-derived dendritic cells.
abstract: SAMHD1 is a viral restriction factor expressed in dendritic cells and other cells, inhibiting infection by cell-free human immunodeficiency virus type 1 (HIV-1) particles. SAMHD1 depletes the intracellular pool of deoxynucleoside triphosphates, thus impairing HIV-1 reverse transcription and productive infection in noncycling cells. The Vpx protein from HIV-2 or simian immunodeficiency virus (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 (MDDCs). HIV-1-infected lymphocytes were cocultivated with MDDCs that have been pretreated or not with Vpx or with small interfering RNA against SAMHD1. We show that in the cocultures, SAMHD1 significantly inhibits productive cell-to-cell transmission to target MDDCs and prevents the type I interferon response and expression of the interferon-stimulated gene MxA. Therefore, SAMHD1, by controlling the sensitivity of MDDCs to HIV-1 infection during intercellular contacts, impacts their ability to sense the virus and to trigger an innate immune response.
authors.affiliation: Institut Pasteur, Unité Virus et Immunité, Département de Virologie, and CNRS, URA3015, Paris, France.
authors.forename: Isabel
authors.initials: I
authors.lastname: Puigdomènech
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Casartelli
authors.forename: Françoise
authors.initials: F
authors.lastname: Porrot
authors.forename: Olivier
authors.initials: O
authors.lastname: Schwartz
mesh_terms: D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology*; D019204:GTP-Binding Proteins / Q000096:biosynthesis; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D064547:Myxovirus Resistance Proteins; D034622:RNA Interference; D034741:RNA, Small Interfering; D000076106:SAM Domain and HD Domain-Containing Protein 1; D013601:T-Lymphocytes / Q000821:virology*; D054334:Viral Regulatory and Accessory Proteins / Q000502:physiology; D014779:Virus Replication
chemical_list: D007370:Interferon Type I; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D034741:RNA, Small Interfering; C074286:VPX protein, Human immunodeficiency virus 2; D054334:Viral Regulatory and Accessory Proteins; D000076106:SAM Domain and HD Domain-Containing Protein 1; C484280:SAMHD1 protein, human; D019204:GTP-Binding Proteins; D020559:Monomeric GTP-Binding Proteins