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Inhibition of measles virus budding by phenothiazines
Abstract:
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.
Insights
Anticalmodulin drugs trifluoperazine and chlorpromazine arrest measles virus budding at the plasma membrane. This inhibition, dependent on extracellular calcium, likely stems from impaired viral cytoskeleton interactions.
Area of Science:
- Virology
- Cell Biology
- Pharmacology
Background:
- Measles virus assembly involves budding from the host cell plasma membrane.
- Anticalmodulin drugs like trifluoperazine (TFP) and chlorpromazine (CPZ) can affect cellular processes.
Purpose of the Study:
- To investigate the effect of TFP and CPZ on measles virus budding.
- To elucidate the mechanism by which these drugs inhibit virus release.
Main Methods:
- Infection of HeLa cells with measles virus.
- Treatment with TFP and CPZ at various concentrations.
- Observation of virus particle morphology and localization.
- Assessment of drug effects on viral protein synthesis via immunoprecipitation.
- Analysis of viral structure interaction with the cytoskeleton using cytochalasin B.
Main Results:
- TFP and CPZ caused accumulation of measles virus-specific strands at the plasma membrane, with a reduction in spherical particles.
- The inhibitory effect at low drug concentrations was dependent on extracellular calcium.
- Virus budding resumed after drug removal, independent of cycloheximide, indicating no qualitative change in viral protein synthesis.
- Viral strands did not comigrate with cytochalasin B-induced actin patches, suggesting cytoskeletal involvement.
Conclusions:
- TFP and CPZ arrest measles virus budding at an intermediate stage at the plasma membrane.
- The inhibition mechanism likely involves impaired interaction between viral structures and the host cell cytoskeleton.