Document 0873
 DOCN  M9540873
 TI    Expression of a Tat-inducible herpes simplex virus-thymidine kinase gene
       protects acyclovir-treated CD4 cells from HIV-1 spread by conditional
       suicide and inhibition of reverse transcription.
 DT    9504
 AU    Caruso M; Salomon B; Zhang S; Brisson E; Clavel F; Lowy I; Klatzmann D;
       Laboratoire de Biologie et Genetique des Pathologies; Immunitaires, CNRS
       URA D1463, Hopital de la; Pitie-Salpetriere, Paris, France.
 SO    Virology. 1995 Jan 10;206(1):495-503. Unique Identifier : AIDSLINE
       MED/95133185
 AB    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 microM 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.
 DE    Acyclovir/*PHARMACOLOGY  Cell Death/DRUG EFFECTS  Cell Line
       CD4-Positive T-Lymphocytes/CYTOLOGY/*DRUG EFFECTS/VIROLOGY  Gene
       Products, tat/PHYSIOLOGY  HIV-1/DRUG EFFECTS/*PHYSIOLOGY
       Simplexvirus/*ENZYMOLOGY/GENETICS  Support, Non-U.S. Gov't  Thymidine
       Kinase/GENETICS/*METABOLISM  Trans-Activation (Genetics)
       *Transcription, Genetic/DRUG EFFECTS  Virus Replication  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).