Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Acyclovir is activated into a HIV-1 reverse transcriptase inhibitor in herpesvirus-infected human tissues

Lisco, Andrea, Vanpouille, Christophe, Tchesnokov, Egor P., Grivel, Jean Charles, Biancotto, Angélique, Brichacek, Beda, Elliott, Julie, Fromentin, Emilie, Shattock, Robert, Anton, Peter, Gorelick, Robert, Balzarini, Jan, McGuigan, Christopher, Derudas, Marco, Gotte, Matthias, Schinazi, Raymond F. and Margolis, Leonid. 2008. Acyclovir is activated into a HIV-1 reverse transcriptase inhibitor in herpesvirus-infected human tissues. Cell Host & Microbe 4 (3) , pp. 260-270. 10.1016/j.chom.2008.07.008

Full text not available from this repository.

Abstract

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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Pharmacy
Systems Immunity Research Institute (SIURI)
Subjects: R Medicine > RM Therapeutics. Pharmacology
Publisher: Elsevier
ISSN: 1931-3128
Last Modified: 18 Oct 2017 13:13
URI: http://orca.cf.ac.uk/id/eprint/6622

Citation Data

Cited 116 times in Google Scholar. View in Google Scholar

Cited 91 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item