@article{b0d7802d2359415ca64af86eabc0b2f2,
title = "SAMHD1 restricts HIV-1 infection in resting CD4 + T cells",
abstract = "Unlike activated CD4 + T cells, resting CD4 + T cells are highly resistant to productive HIV-1 infection. Early after HIV-1 entry, a major block limits reverse transcription of incoming viral genomes. Here we show that the deoxynucleoside triphosphate triphosphohydrolase SAMHD1 prevents reverse transcription of HIV-1 RNA in resting CD4 + T cells. SAMHD1 is abundantly expressed in resting CD4 + T cells circulating in peripheral blood and residing in lymphoid organs. The early restriction to infection in unstimulated CD4 + T cells is overcome by HIV-1 or HIV-2 virions into which viral Vpx is artificially or naturally packaged, respectively, or by addition of exogenous deoxynucleosides. Vpx-mediated proteasomal degradation of SAMHD1 and elevation of intracellular deoxynucleotide pools precede successful infection by Vpx-carrying HIV. Resting CD4 + T cells from healthy donors following SAMHD1 silencing or from a patient with Aicardi-Gouti{\`e}res syndrome homozygous for a nonsense mutation in SAMHD1 were permissive for HIV-1 infection. Thus, SAMHD1 imposes an effective restriction to HIV-1 infection in the large pool of noncycling CD4 + T cells in vivo. Bypassing SAMHD1 was insufficient for the release of viral progeny, implicating other barriers at later stages of HIV replication. Together, these findings may unveil new ways to interfere with the immune evasion and T cell immunopathology of pandemic HIV-1.",
author = "Baldauf, {Hanna Mari} and Xiaoyu Pan and Elina Erikson and Sarah Schmidt and Waaqo Daddacha and Manja Burggraf and Kristina Schenkova and Ina Ambiel and Guido Wabnitz and Thomas Gramberg and Sylvia Panitz and Egbert Flory and Landau, {Nathaniel R.} and Serkan Sertel and Frank Rutsch and Felix Lasitschka and Baek Kim and Renate K{\"o}nig and Fackler, {Oliver T.} and Keppler, {Oliver T.}",
note = "Funding Information: We thank M. Emerman (Fred Hutchinson Cancer Research Center, Seattle, USA; for pROD9, pROD9-∆Env-GFP, pROD9-∆Env-delVpx-GFP), M. Fujita (Research Institute for Drug Discovery, Kumamoto University, Japan; for pEF-FVpxHIV-2GH1), H.-G. Kr{\"a}usslich (Department of Infectious Diseases, Virology, University of Heidelberg, Germany; for AMD3100), B. M{\"u}ller (Department of Infectious Diseases, Virology, University of Heidelberg, Germany; for pDisplay GFP and sheep anti–HIV-1 p24 antibody) and J. M{\"u}nch (Institute of Molecular Virology, University Hospital Ulm, Germany; for HIV-1 GFP) for reagents. We thank T. Adam, A. Imle, P. Klein, S. Kutscheidt, A. Ruggieri and the Nikon Imaging Center at University of Heidelberg for technical assistance, and G. Howard for editorial assistance. This work was in part funded by the Deutsche Forschungsgemeinschaft (O.T.K., grant KE742/4-1), SFB 938/Z2 (F.L.) and the US National Institutes of Health (GM1041981 and AI049781 to B.K.; and F31 GM095190 to W.D.). O.T.F. and O.T.K. are members of the CellNetworks Cluster of Excellence EXC81 and the German Centre for Infection Research, University of Heidelberg. H.-M.B. is recipient of a fellowship of the Medical Faculty of the University of Heidelberg.",
year = "2012",
month = nov,
doi = "10.1038/nm.2964",
language = "English (US)",
volume = "18",
pages = "1682--1687",
journal = "Nature Medicine",
issn = "1078-8956",
publisher = "Nature Publishing Group",
number = "11",
}