Inhibition of herpes simplex virus production in vitro by cyclosporin A.
Nontoxic concentrations of Cyclosporin A (CyA) dose-dependently inhibited herpes simplex virus (HSV) production in resting monkey kidney cells. The block was at the step of virus DNA synthesis as assessed by [3H]thymidine incorporation and by dot blot hybridization of infected cell DNA using a cloned 32P-labelled HSV DNA fragment (BamHI X) as probe. This was further supported by analysis of HSV protein synthesis in the presence of CyA as assessed by sodium dodecyl sulphate polyacrylamide gel electrophoresis and Western blot. A relative accumulation of HSV alpha- (e.g., ICP 4) and beta 1-proteins (e.g., ICP 6 and 8) was found, whereas HSV gamma 1-proteins were slightly decreased and gamma 2-proteins were markedly decreased by CyA. The production of thymidine kinase and DNA polymerase was decreased when CyA was added to HSV infected cells. The sensitivity to CyA was not escaped by thymidine kinase nor DNA polymerase deficient mutants. Passage of HSV in presence of CyA did not result in induction of drug resistance.
Vahlne
A
A
Department of Clinical Virology, University of Göteborg, Sweden.
Larsson
P A
PA
Horal
P
P
Ahlmén
J
J
Svennerholm
B
B
Gronowitz
J S
JS
Olofsson
S
S
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology* / Q000627:therapeutic use; D004279:DNA, Viral / Q000096:biosynthesis; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D004351:Drug Resistance / Q000235:genetics; D009154:Mutation; D018139:Simplexvirus / Q000187:drug effects* / Q000502:physiology; D013937:Thymidine Kinase / Q000378:metabolism; D014764:Viral Proteins / Q000096:biosynthesis; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D004279:DNA, Viral; D014764:Viral Proteins; D016572:Cyclosporine; D013937:Thymidine Kinase; D004259:DNA-Directed DNA Polymerase