Imperial College London
Alternate

Emeritus ProfessorJonathanStoye

Faculty of Medicine, Department of Infectious Disease

Emeritus Professor of Endogenous Retroviruses
 
 
 
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Contact

 

j.stoye Website

 
 
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Location

 

Francis Crick InstituteThe Francis Crick Institute

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Summary

 

Publications

Citation

BibTex format

@article{Ordonez:2017:10.1038/srep42824,
author = {Ordonez, P and Kunzelmann, S and Groom, HCT and Yap, MW and Weising, S and Meier, C and Bishop, KN and Taylor, IA and Stoye, JP},
doi = {10.1038/srep42824},
journal = {Scientific Reports},
title = {SAMHD1 enhances nucleoside-analogue efficacy against HIV-1 in myeloid cells},
url = {http://dx.doi.org/10.1038/srep42824},
volume = {7},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - SAMHD1 is an intracellular enzyme that specifically degrades deoxynucleoside triphosphates intocomponent nucleoside and inorganic triphosphate. In myeloid-derived dendritic cells and macrophagesas well as resting T-cells, SAMHD1 blocks HIV-1 infection through this dNTP triphosphohydrolaseactivity by reducing the cellular dNTP pool to a level that cannot support productive reversetranscription. We now show that, in addition to this direct effect on virus replication, manipulatingcellular SAMHD1 activity can significantly enhance or decrease the anti-HIV-1 efficacy of nucleotideanalogue reverse transcription inhibitors presumably as a result of modulating dNTP pools thatcompete for recruitment by viral polymerases. Further, a variety of other nucleotide-based analogues,not normally considered antiretrovirals, such as the anti-herpes drugs Aciclovir and Ganciclovir and theanti-cancer drug Clofarabine are now revealed as potent anti-HIV-1 agents, under conditions of lowdNTPs. This in turn suggests novel uses for nucleotide analogues to inhibit HIV-1 in differentiated cellslow in dNTPs.
AU  - Ordonez,P
AU  - Kunzelmann,S
AU  - Groom,HCT
AU  - Yap,MW
AU  - Weising,S
AU  - Meier,C
AU  - Bishop,KN
AU  - Taylor,IA
AU  - Stoye,JP
DO  - 10.1038/srep42824
PY  - 2017///
SN  - 2045-2322
TI  - SAMHD1 enhances nucleoside-analogue efficacy against HIV-1 in myeloid cells
T2  - Scientific Reports
UR  - http://dx.doi.org/10.1038/srep42824
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000394711600001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/71512
VL  - 7
ER  -
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