Expression of a Tat-inducible herpes simplex virus-thymidine kinase gene protectsacyclovir-treated CD4 cells from HIV-1 spread by conditional suicide and inhibition of reverse transcription

Manuel Caruso, Benoit Salomon, Su Zhang, Edith Brisson, François Clavel, Israel Lowy, David Klatzmann

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Cellular expression of the herpes simplex virus type 1 thymidine kinase (HSV1-TK) gene promotes cell death in the presence of specific nucleoside analog substrates such as acyclovir (ACV). We have reported that lymphoid CD4+ cells harboring an HSV1-TK gene, under the transcriptional control of the HIV-1 long terminal repeat (HUT-TK), are completely protected from HIV-1 spread in the presence of 10 μM ACV. In this report we clarify the efficiency, generality, and mechanism of this protective effect. We show that the protection from HIV-1 spread in HUT-TK cells obtains from both an inhibition of HIV reverse transcription by ACV metabolites and an HIV-induced and ACV-dependent cell killing. We also demonstrate that monocytic cells harboring the HIV-1-inducible HSV1-TK gene are protected from HIV spread in the presence of ACV. These observations facilitate the design of therapeutic strategies to limit HIV replication based on HSV1-TK expression.

Original languageEnglish
Pages (from-to)495-503
Number of pages9
JournalVirology
Volume206
Issue number1
DOIs
StatePublished - 10 Jan 1995
Externally publishedYes

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