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

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Lahouassa, Hichem, Daddacha, Waaqo, Hofmann, Henning, Ayinde, Diana, Logue, Eric C, Dragin, Loïc, Bloch, Nicolin, Maudet, Claire +11 more·2012·Nature Immunology
DOI 10.1038/ni.2236PMC PMC3771401
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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.

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  • SAMHD1 inhibits reverse transcription by depleting the cellular pool of deoxynucleotide triphosphates.

    “For example, sterile alpha motif and HD domain 1 (SAMHD1) inhibits reverse transcription by depleting the cellular pool of deoxynucleotide triphosphates [63,64]”

    From HIV-1 and HTLV-1 Transmission Modes: Mechanisms and Importance for Virus Spread (2022) · cites this paper as [64]

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Authors
Lahouassa, H., Daddacha, W., Hofmann, H., Ayinde, D., Logue, E. C., Dragin, L., Bloch, N., Maudet, C., Bertrand, M., Gramberg, T., Pancino, G., Priet, S., Canard, B., Laguette, N., Benkirane, M., Transy, C., Landau, N. R., Kim, B., & Margottin-Goguet, F.
Affiliations
  • Centre National de la Recherche Scientifique (FR)
  • University of Rochester Medicine (US)
  • New York University (US)
  • Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
  • Institut Pasteur (FR)
Corresponding author
  • Landau, Nathaniel R
  • Kim, Baek
  • Margottin-Goguet, Florence
ORCID
Venue
Nature Immunology
Publisher
Springer Science and Business Media LLC
Published
2012-02-12
Volume
13
Issue
3
Pages
223-228
ISSN
  • 1529-2908 (ISSN-L)
  • 1529-2916
DOI
10.1038/ni.2236
PMC
PMC3771401
OpenAlex
W1992007798
Cited by
852
References
4
Citations by year
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FWCI
44.27
Type
journal article
Language
en
Update notices
Open access
Licence
Locations
  • Nature Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • HAL (submittedVersion)
Funders
  • U.S. Public Health Service (A1077401, A1067059)
  • National Institute of General Medical Sciences (F31GM095190, R01GM104198)
  • National Institute of Allergy and Infectious Diseases (R56AI049781, R01AI049781, AI049781)
Topics
  • Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
  • Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
Keywords
SAMHD1, HIV-1, deoxyribonucleoside triphosphates, Vpx, reverse transcriptase, antiviral restriction, dendritic cells, myeloid cells, nucleotide hydrolysis
MeSH terms
SAM Domain and HD Domain-Containing Protein 1, Animals, Cell Line, Humans, Macaca mulatta, Macrophages, Nucleotides, Virus Replication, HIV-1, Monomeric GTP-Binding Proteins, Intracellular Space, Mice

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