Imperial College London
Alternate

ProfessorRobinShattock

Faculty of Medicine, Department of Infectious Disease

Chair in Mucosal Infection and Immunity
 
 
 
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Contact

 

+44 (0)20 7594 5206r.shattock

 
 
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Location

 

453Wright Fleming WingSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Lisco:2008:10.1016/j.chom.2008.07.008,
author = {Lisco, A and Vanpouille, C and Tchesnokov, EP and Grivel, J-C and Biancotto, A and Brichacek, B and Elliott, J and Fromentin, E and Shattock, R and Anton, P and Gorelick, R and Balzarini, J and McGuigan, C and Derudas, M and Götte, M and Schinazi, RF and Margolis, L},
doi = {10.1016/j.chom.2008.07.008},
journal = {Cell Host Microbe},
pages = {260--270},
title = {Acyclovir is activated into a HIV-1 reverse transcriptase inhibitor in herpesvirus-infected human tissues.},
url = {http://dx.doi.org/10.1016/j.chom.2008.07.008},
volume = {4},
year = {2008}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - For most viruses, there is a need for antimicrobials that target unique viral molecular properties. Acyclovir (ACV) is one such drug. It is activated into a human herpesvirus (HHV) DNA polymerase inhibitor exclusively by HHV kinases and, thus, does not suppress other viruses. Here, we show that ACV suppresses HIV-1 in HHV-coinfected human tissues, but not in HHV-free tissue or cell cultures. However, addition of HHV-6-infected cells renders these cultures sensitive to anti-HIV ACV activity. We hypothesized that such HIV suppression requires ACV phosphorylation by HHV kinases. Indeed, an ACV monophosphorylated prodrug bypasses the HHV requirement for HIV suppression. Furthermore, phosphorylated ACV directly inhibits HIV-1 reverse transcriptase (RT), terminating DNA chain elongation, and can trap RT at the termination site. These data suggest that ACV anti-HIV-1 activity may contribute to the response of HIV/HHV-coinfected patients to ACV treatment and could guide strategies for the development of new HIV-1 RT inhibitors.
AU  - Lisco,A
AU  - Vanpouille,C
AU  - Tchesnokov,EP
AU  - Grivel,J-C
AU  - Biancotto,A
AU  - Brichacek,B
AU  - Elliott,J
AU  - Fromentin,E
AU  - Shattock,R
AU  - Anton,P
AU  - Gorelick,R
AU  - Balzarini,J
AU  - McGuigan,C
AU  - Derudas,M
AU  - Götte,M
AU  - Schinazi,RF
AU  - Margolis,L
DO  - 10.1016/j.chom.2008.07.008
EP  - 270
PY  - 2008///
SP  - 260
TI  - Acyclovir is activated into a HIV-1 reverse transcriptase inhibitor in herpesvirus-infected human tissues.
T2  - Cell Host Microbe
UR  - http://dx.doi.org/10.1016/j.chom.2008.07.008
UR  - https://www.ncbi.nlm.nih.gov/pubmed/18779052
VL  - 4
ER  -
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