dc.contributor.author |
Goldstone, David |
en |
dc.contributor.author |
Ennis-Adeniran, V |
en |
dc.contributor.author |
Hedden, JJ |
en |
dc.contributor.author |
Groom, HCT |
en |
dc.contributor.author |
Rice, GI |
en |
dc.contributor.author |
Christodoulou, E |
en |
dc.contributor.author |
Walker, PA |
en |
dc.contributor.author |
Kelly, G |
en |
dc.contributor.author |
Haire, LF |
en |
dc.contributor.author |
Yap, MW |
en |
dc.contributor.author |
de Carvalho, LPS |
en |
dc.contributor.author |
Stoye, JP |
en |
dc.contributor.author |
Crow, YJ |
en |
dc.contributor.author |
Taylor, IA |
en |
dc.contributor.author |
Webb, M |
en |
dc.date.accessioned |
2012-05-13T21:30:37Z |
en |
dc.date.issued |
2011-12-15 |
en |
dc.identifier.citation |
NATURE 480(7377):379-383 15 Dec 2011 |
en |
dc.identifier.issn |
0028-0836 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/17932 |
en |
dc.description.abstract |
SAMHD1, an analogue of the murine interferon (IFN)-gamma-induced gene Mg11 (ref. 1), has recently been identified as a human immunodeficiency virus-1 (HIV-1) restriction factor that blocks early-stage virus replication in dendritic and other myeloid cells(2,3) and is the target of the lentiviral protein Vpx, which can relieve HIV-1 restriction(4-7). SAMHD1 is also associated with Aicardi-Goutieres syndrome (AGS), an inflammatory encephalopathy characterized by chronic cerebrospinal fluid lymphocytosis and elevated levels of the antiviral cytokine IFN-alpha(8). The pathology associated with AGS resembles congenital viral infection, such as transplacentally acquired HIV. Here we show that human SAMHD1 is a potent dGTP-stimulated triphosphohydrolase that converts deoxynucleoside triphosphates to the constituent deoxynucleoside and inorganic triphosphate. The crystal structure of the catalytic core of SAMHD1 reveals that the protein is dimeric and indicates a molecular basis for dGTP stimulation of catalytic activity against dNTPs. We propose that SAMHD1, which is highly expressed in dendritic cells, restricts HIV-1 replication by hydrolysing the majority of cellular dNTPs, thus inhibiting reverse transcription and viral complementary DNA (cDNA) synthesis. |
en |
dc.language |
English |
en |
dc.publisher |
NATURE PUBLISHING GROUP |
en |
dc.relation.ispartofseries |
NATURE |
en |
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from http://www.sherpa.ac.uk/romeo/issn/0028-0836/ |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.subject |
Science & Technology |
en |
dc.subject |
Multidisciplinary Sciences |
en |
dc.subject |
Science & Technology - Other Topics |
en |
dc.subject |
AICARDI-GOUTIERES-SYNDROME |
en |
dc.subject |
HUMAN DENDRITIC CELLS |
en |
dc.subject |
REVERSE-TRANSCRIPTASE |
en |
dc.subject |
DNTP TRIPHOSPHOHYDROLASE |
en |
dc.subject |
INFECTION |
en |
dc.subject |
PROTEIN |
en |
dc.subject |
VPX |
en |
dc.subject |
MACROPHAGE |
en |
dc.subject |
MUTATIONS |
en |
dc.subject |
TREX1 |
en |
dc.title |
HIV-1 restriction factor SAMHD1 is a deoxynucleoside triphosphate triphosphohydrolase |
en |
dc.type |
Journal Article |
en |
dc.identifier.doi |
10.1038/nature10623 |
en |
pubs.issue |
7377 |
en |
pubs.begin-page |
379 |
en |
pubs.volume |
480 |
en |
dc.rights.holder |
Copyright: NATURE PUBLISHING GROUP |
en |
dc.identifier.pmid |
22056990 |
en |
pubs.author-url |
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=000298033000054&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=6e41486220adb198d0efde5a3b153e7d |
en |
pubs.end-page |
383 |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/RestrictedAccess |
en |
pubs.subtype |
Article |
en |
pubs.elements-id |
285407 |
en |
pubs.org-id |
Science |
en |
pubs.org-id |
Biological Sciences |
en |
dc.identifier.eissn |
1476-4687 |
en |
pubs.record-created-at-source-date |
2013-06-05 |
en |
pubs.dimensions-id |
22056990 |
en |