University of Sussex
Browse
1-s2.0-S1931312808002278-main.pdf (1007.88 kB)

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

Download (1007.88 kB)
journal contribution
posted on 2023-06-08, 21:54 authored by Andrea Lisco, Christophe Vanpouille, Egor P Tchesnokov, Jean-Charles Grivel, Angélique Biancotto, Beda Brichacek, Julie Elliott, Emilie Fromentin, Robin Shattock, Peter Anton, Robert Gorelick, Jan Balzarini, Christopher McGuigan, Marco Derudas, Matthias Götte, Raymond F Schinazi, Leonid Margolis
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.

History

Publication status

  • Published

File Version

  • Published version

Journal

Cell Host and Microbe

ISSN

1931-3128

Publisher

Elsevier

Issue

3

Volume

4

Page range

260-270

Department affiliated with

  • Chemistry Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2015-07-28

First Open Access (FOA) Date

2015-07-28

First Compliant Deposit (FCD) Date

2015-07-28

Usage metrics

    University of Sussex (Publications)

    Categories

    No categories selected

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC