Conditional reduction of human immunodeficiency virus type 1 replication by a gain-of-herpes simplex virus 1 thymidine ase function

Stephen M. Smith, Richard B. Markham, Kuan Teh Jeang

Research output: Contribution to journalArticle


The development of an effective vaccine for human immunodeficiency virus type 1 (HIV-1) would be a major advance toward controlling the AIDS pandemic. Several disparate strategies for a safe and effective HIV vaccine have been proposed. Recent data suggest that loss-of-function live-attenuated virus could be a safe lentivirus vaccine. Here, we propose a gain-of-function approach that can complement loss-of-function in enhancing the safety profile of a live-attenuated virus. We describe an example in which ganciclovir (GCV) was used to treat effectively nef(-) HIV-1 engineered to express herpes simplex virus (HSV-1) thymidine kinase (TK). This treatment was found to be highly efficient in controlling HIV-1 spread in tissue culture and in a small animal (hu-PBL-SCID) model. We demonstrate that one distinct advantage of GCV-HSV-TK treatment is the elimination of integrated proviruses, a goal not easily achieved with other antiretrovirals.

Original languageEnglish (US)
Pages (from-to)7955-7960
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number15
StatePublished - Jul 23 1996



  • Antiviral chemotherapy
  • Virus replication

ASJC Scopus subject areas

  • General

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