Inhibition of measles virus budding by phenothiazines.
HeLa cells infected with measles virus show an accumulation of virus-specific strands at the plasma membrane after addition of the anticalmodulin drugs trifluoperazine (TFP) and chlorpromazine (CPZ), whereas spherical virus particles are almost completely absent. At low drug concentrations (10-15 microM TFP; 30-40 microM CPZ) the inhibitory effect is dependent on the presence of extracellular calcium. The strands complete the budding process after removal of the drugs. Restoration of virus budding is not sensitive to cycloheximide and immunoprecipitation experiments give evidence that the viral protein synthesis is not qualitatively altered in the presence of TFP. The data indicate that both drugs arrest the budding process at an intermediate stage at the plasma membrane. The inability of the strands to comigrate with cytochalasin B-induced actin patches suggests that the inhibition of budding is probably the result of an impaired interaction of viral structures with the cytoskeleton.
D014150:Antipsychotic Agents / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D002462:Cell Membrane / Q000382:microbiology; D002746:Chlorpromazine / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D003571:Cytochalasin B / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D006367:HeLa Cells / Q000382:microbiology; D006801:Humans; D008459:Measles virus / Q000187:drug effects* / Q000502:physiology; D008855:Microscopy, Electron, Scanning; D011233:Precipitin Tests; D014268:Trifluoperazine / Q000494:pharmacology; D014776:Virus Cultivation; D014779:Virus Replication / Q000187:drug effects*
D014150:Antipsychotic Agents; D014268:Trifluoperazine; D003571:Cytochalasin B; D003513:Cycloheximide; D002118:Calcium; D002746:Chlorpromazine