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PMID: 22327569 Published · epublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

SAMHD1 restricts the replication of human immunodeficiency virus type 1 by depleting the intracellular pool of deoxynucleoside triphosphates.

Nature immunology ·Vol. 13 ·No. 3 ·2012-02-12 ·Pages 223-228

Lahouassa H, Daddacha W, Hofmann H, Ayinde D, Logue EC, Dragin L, Bloch N, Maudet C, Bertrand M, Gramberg T, Pancino G, Priet S, Canard B, Laguette N, Benkirane M, Transy C, Landau NR, Kim B, Margottin-Goguet F

Abstract

SAMHD1 restricts the infection of dendritic and other myeloid cells by human immunodeficiency virus type 1 (HIV-1), but in lentiviruses of the simian immunodeficiency virus of sooty mangabey (SIVsm)-HIV-2 lineage, SAMHD1 is counteracted by the virion-packaged accessory protein Vpx. Here we found that SAMHD1 restricted infection by hydrolyzing intracellular deoxynucleoside triphosphates (dNTPs), lowering their concentrations to below those required for the synthesis of the viral DNA by reverse transcriptase (RT). SAMHD1-mediated restriction was alleviated by the addition of exogenous deoxynucleosides. An HIV-1 with a mutant RT with low affinity for dNTPs was particularly sensitive to SAMHD1-mediated restriction. Vpx prevented the SAMHD1-mediated decrease in dNTP concentration and induced the degradation of human and rhesus macaque SAMHD1 but had no effect on mouse SAMHD1. Nucleotide-pool depletion could be a general mechanism for protecting cells from infectious agents that replicate through a DNA intermediate.

MeSH Terms
Animals Cell Line HIV-1/physiology Humans Intracellular Space/metabolism Macaca mulatta Macrophages/immunology Mice Monomeric GTP-Binding Proteins/genetics,immunology,metabolism Nucleotides/metabolism SAM Domain and HD Domain-Containing Protein 1 Virus Replication
Chemicals
Nucleotides SAM Domain and HD Domain-Containing Protein 1 SAMHD1 protein, human Samhd1 protein, mouse Monomeric GTP-Binding Proteins
Authors & Affiliations
19 authors, click to expand affiliations / ORCID
Lahouassa Hichem
Inserm, U1016, Institut Cochin, 27 rue du faubourg St Jacques, Bat G. Roussy, 75014 Paris France. | Cnrs, UMR8104, Paris, France. | Univ Paris Descartes, Paris, France.
Daddacha Waaqo
Department of Microbiology and Immunology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA.
Hofmann Henning
New York University School of Medicine, Microbiology Department, 550 First Ave., New York, NY 10016, USA.
Ayinde Diana
Inserm, U1016, Institut Cochin, 27 rue du faubourg St Jacques, Bat G. Roussy, 75014 Paris France. | Cnrs, UMR8104, Paris, France. | Univ Paris Descartes, Paris, France.
Logue Eric C
New York University School of Medicine, Microbiology Department, 550 First Ave., New York, NY 10016, USA.
Dragin Loïc
Inserm, U1016, Institut Cochin, 27 rue du faubourg St Jacques, Bat G. Roussy, 75014 Paris France. | Cnrs, UMR8104, Paris, France. | Univ Paris Descartes, Paris, France.
Bloch Nicolin
New York University School of Medicine, Microbiology Department, 550 First Ave., New York, NY 10016, USA.
Maudet Claire
Inserm, U1016, Institut Cochin, 27 rue du faubourg St Jacques, Bat G. Roussy, 75014 Paris France. | Cnrs, UMR8104, Paris, France. | Univ Paris Descartes, Paris, France.
Bertrand Matthieu
Inserm, U1016, Institut Cochin, 27 rue du faubourg St Jacques, Bat G. Roussy, 75014 Paris France. | Cnrs, UMR8104, Paris, France. | Univ Paris Descartes, Paris, France.
Gramberg Thomas
Virologisches Institut, Klinische und Molekulare Virologie, Universitat Erlangen-Nurnberg, 91054 Erlangen.
Pancino Gianfranco
Institut Pasteur, Unité de Régulation des Infections Rétrovirales, 25 rue du Dr Roux, 75724 Paris Cedex 15, France.
Priet Stéphane
Laboratoire d'Architecture et Fonction des Macromolécules Biologiques, UMR6098, CNRS-Universitéd'Aix-Marseille, 13288 Marseille cedex 09, France.
Canard Bruno
Laboratoire d'Architecture et Fonction des Macromolécules Biologiques, UMR6098, CNRS-Universitéd'Aix-Marseille, 13288 Marseille cedex 09, France.
Laguette Nadine
Institut de Génétique Humaine, Laboratoire de Virologie Moléculaire, CNRS UPR1142, Montpellier 34000, France.
Benkirane Monsef
Institut de Génétique Humaine, Laboratoire de Virologie Moléculaire, CNRS UPR1142, Montpellier 34000, France.
Transy Catherine
Inserm, U1016, Institut Cochin, 27 rue du faubourg St Jacques, Bat G. Roussy, 75014 Paris France. | Cnrs, UMR8104, Paris, France. | Univ Paris Descartes, Paris, France.
Landau Nathaniel R
New York University School of Medicine, Microbiology Department, 550 First Ave., New York, NY 10016, USA.
Kim Baek
Department of Microbiology and Immunology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA.
Margottin-Goguet Florence
Inserm, U1016, Institut Cochin, 27 rue du faubourg St Jacques, Bat G. Roussy, 75014 Paris France. | Cnrs, UMR8104, Paris, France. | Univ Paris Descartes, Paris, France.
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Article Info
Journal
Nature immunology
Abbr.
Nat Immunol
ISSN
1529-2916
DOI
10.1038/ni.2236
Published
2012-02-12
Epub
2012-00-12
Pages
223-228
Language
English
Region
United States
NLM ID
100941354
PMCID
PMC3771401
Subset
IM
Grants
European Research Council · 250333 · International
PHS HHS · A1067059 · United States
PHS HHS · A1077401 · United States
NIAID NIH HHS · AI049781 · United States
NIGMS NIH HHS · F31 GM095190 · United States
NIAID NIH HHS · R01 AI049781 · United States
NIGMS NIH HHS · R01 GM104198 · United States
Corrections
ErratumIn
-
CommentIn
PMID: 22392493
External Links
PubMed source DOI: 10.1038/ni.2236 PMC Full Text View journal details
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