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

被引：664

作者：

Lahouassa, Hichem ^{[2
,3
,4
]}

Daddacha, Waaqo ^{[5
]}

Hofmann, Henning ^{[1
]}

Ayinde, Diana ^{[2
,3
,4
]}

Logue, Eric C. ^{[1
]}

Dragin, Loic ^{[2
,3
,4
]}

Bloch, Nicolin ^{[1
]}

Maudet, Claire ^{[2
,3
,4
]}

Bertrand, Matthieu ^{[2
,3
,4
]}

Gramberg, Thomas ^{[6
]}

Pancino, Gianfranco ^{[7
]}

Priet, Stephane ^{[8
]}

Canard, Bruno ^{[8
]}

Laguette, Nadine ^{[9
]}

Benkirane, Monsef ^{[9
]}

Transy, Catherine ^{[2
,3
,4
]}

Landau, Nathaniel R. ^{[1
]}

Kim, Baek ^{[5
]}

Margottin-Goguet, Florence ^{[2
,3
,4
]}

机构：

[1] NYU, Sch Med, Dept Microbiol, New York, NY 10016 USA

[2] Inst Natl Sante & Rech Med U1016, Inst Cochin, Paris, France

[3] Ctr Natl Rech Sci, UMR8104, Paris, France

[4] Univ Paris 05, Paris, France

[5] Univ Rochester, Med Ctr, Dept Microbiol & Immunol, Rochester, NY 14642 USA

[6] Univ Erlangen Nurnberg, Inst Virol, D-91054 Erlangen, Germany

[7] Inst Pasteur, Unite Regulat Infect Retrovirales, Paris, France

[8] Univ Aix Marseille, Lab Architecture & Fonct Macromol Biol, UMR6098, Ctr Natl Rech Sci, Marseille, France

[9] Ctr Natl Rech Sci UPR1142, Inst Genet Humaine, Mol Virol Lab, Montpellier, France

来源：

NATURE IMMUNOLOGY | 2012年 / 13卷 / 03期

基金：

美国国家卫生研究院; 欧洲研究理事会;

关键词：

HUMAN DENDRITIC CELLS; MITOCHONDRIAL-DNA DEPLETION; AICARDI-GOUTIERES-SYNDROME; INNATE IMMUNE-RESPONSE; REVERSE-TRANSCRIPTASE; RIBONUCLEOTIDE REDUCTASE; MONONUCLEAR PHAGOCYTES; HUMAN MACROPHAGES; BINDING PROTEIN; VPX;

D O I：

10.1038/ni.2236

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：223 / +

页数：2

共 49 条

[1] APOBEC3A Is a Specific Inhibitor of the Early Phases of HIV-1 Infection in Myeloid Cells
Berger, Gregory
Durand, Stephanie
Fargier, Guillaume
Xuan-Nhi Nguyen
Cordeil, Stepanie
Bouaziz, Serge
Muriaux, Delphine
Darlix, Jean-Luc
Cimarelli, Andrea
[J]. PLOS PATHOGENS, 2011, 7 (09)
[2] A simple, versatile and efficient method to genetically modify human monocyte-derived dendritic cells with HIV-1-derived lentiviral vectors
Berger, Gregory
Durand, Stephanie
Goujon, Caroline
Xuan-Nhi Nguyen
Cordeil, Stephanie
Darlix, Jean-Luc
Cimarelli, Andrea
[J]. NATURE PROTOCOLS, 2011, 6 (06) : 806 - 816
[3] Mutation of RRM2B, encoding p53-controlled ribonucleotide reductase (p53R2), causes severe mitochondrial DNA depletion
Bourdon, Alice
Minai, Limor
Serre, Valerie
Jais, Jean-Philippe
Sarzi, Emmanuelle
Aubert, Sophie
Chretien, Dominique
de Lonlay, Pascale
Paquis-Flucklinger, Veronique
Arakawa, Hirofumi
Nakamura, Yusuke
Munnich, Arnold
Rotig, Agnes
[J]. NATURE GENETICS, 2007, 39 (06) : 776 - 780
[4] The first founder DGUOK mutation associated with hepatocerebral mitochondrial DNA depletion syndrome
Brahimi, N.
Jambou, M.
Sarzi, E.
Serre, V.
Boddaert, N.
Romano, S.
de Lonlay, P.
Slama, A.
Munnich, A.
Roetig, A.
Bonnefont, J. P.
Lebre, A. S.
[J]. MOLECULAR GENETICS AND METABOLISM, 2009, 97 (03) : 221 - 226
[5] Elucidation of the role of arg 110 of murine leukemia virus reverse transcriptase in the catalytic mechanism: Biochemical characterization of its mutant enzymes
Chowdhury, K
Kaushik, N
Pandey, VN
Modak, MJ
[J]. BIOCHEMISTRY, 1996, 35 (51) : 16610 - 16620
[6] THE KINETICS OF HUMAN-IMMUNODEFICIENCY-VIRUS REVERSE TRANSCRIPTION ARE SLOWER IN PRIMARY HUMAN MACROPHAGES THAN IN A LYMPHOID-CELL LINE
COLLIN, M
GORDON, S
[J]. VIROLOGY, 1994, 200 (01) : 114 - 120
[7] VPR IS REQUIRED FOR EFFICIENT REPLICATION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 IN MONONUCLEAR PHAGOCYTES
CONNOR, RI
CHEN, BK
CHOE, S
LANDAU, NR
[J]. VIROLOGY, 1995, 206 (02) : 935 - 944
[8] Mutations in the gene encoding the 3′-5′ DNA exonuclease TREX1 cause Aicardi-Goutieres syndrome at the AGS1 locus
Crow, Yanick J.
Hayward, Bruce E.
Parmar, Rekha
Robins, Peter
Leitch, Andrea
Ali, Manir
Black, Deborah N.
van Bokhoven, Hans
Brunner, Han G.
Hamel, Ben C.
Corry, Peter C.
Cowan, Frances M.
Frints, Suzanne G.
Klepper, Joerg
Livingston, John H.
Lynch, Sally Ann
Massey, Roger F.
Meritet, Jean Francois
Michaud, Jacques L.
Ponsot, Gerard
Voit, Thomas
Lebon, Pierre
Bonthron, David T.
Jackson, Andrew P.
Barnes, Deborah E.
Lindahl, Tomas
[J]. NATURE GENETICS, 2006, 38 (08) : 917 - 920
[9] Macrophage tropism of HIV-1 depends on efficient cellular dNTP utilization by reverse transcriptase
Diamond, TL
Roshal, M
Jamburuthugoda, VK
Reynolds, HM
Merriam, AR
Lee, KY
Balakrishnan, M
Bambara, RA
Planelles, V
Dewhurst, S
Kim, B
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (49) : 51545 - 51553
[10] Mechanistic understanding of an altered fidelity simian immunodeficiency virus reverse transcriptase mutation, V148I, identified in a pig-tailed macaque
Diamond, TL
Souroullas, G
Weiss, KK
Lee, KY
Bambara, RA
Dewhurst, S
Kim, B
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (32) : 29913 - 29924

← 1 2 3 4 5 →