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

Hichem Lahouassa, Waaqo Daddacha, Henning Hofmann, Diana Ayinde, Eric C. Logue, Loïc Dragin, Nicolin Bloch, Claire Maudet, Matthieu Bertrand, Thomas Gramberg, Gianfranco Pancino, Stéphane Priet, Bruno Canard, Nadine Laguette, Monsef Benkirane, Catherine Transy, Nathaniel R. Landau, Baek Kim, Florence Margottin-Goguet

Research output: Contribution to journalArticle

493 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)223-228
Number of pages6
JournalNature Immunology
Volume13
Issue number3
DOIs
StatePublished - Mar 1 2012
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

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. (2012). SAMHD1 restricts the replication of human immunodeficiency virus type 1 by depleting the intracellular pool of deoxynucleoside triphosphates. Nature Immunology, 13(3), 223-228. https://doi.org/10.1038/ni.2236