The effect of cicloxolone sodium on the replication of vesicular stomatitis virus in BSC-1 cells.
The effect of cicloxolone sodium (CCX) on the replication of vesicular stomatitis virus (VSV) was investigated. The drug was active during all stages of the virus replication cycle, indicating that it does not operate by the specific inhibition of any single essential virus gene product. The drug reduced the number of VSV particles assembled and released by 100- to 1000-fold. Infectious virus yield was reduced 1000- to 10000-fold, giving a 10-fold or greater increase in the particle/p.f.u. ratio. The reduced number of virus particles produced in the presence of CCX results from two superimposed effects: suppression of VSV secondary transcription and viral protein synthesis, and perturbation of virion assembly. The inhibition of VSV assembly is due to impairment of a Golgi apparatus function related to transport of VSV glycoprotein G to the cell surface, and is characterized by accumulation of viral G and M proteins within the cell. Incubation of VSV-infected cells in the presence of two glycosylation inhibitors, tunicamycin and monensin, similarly leads to intracellular accumulation of G and M proteins, suggesting a common mechanism of action affecting VSV virion assembly. The differential effect of CCX concentration on intracellular levels of the L, N and NS proteins was analysed. CCX also possesses a virucidal effect on mature infectious VSV particles in suspension, 300 microM reducing the VSV titre about 10-fold in 24 h at 4 degrees C or 37 degrees C. The mode of antiviral activity against VSV is compared with that against herpes simplex virus.
Dargan
D J
DJ
MRC Virology Unit, University of Glasgow, U.K.
Galt
C B
CB
Subak-Sharpe
J H
JH
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002229:Carbenoxolone / Q000031:analogs & derivatives* / Q000494:pharmacology; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D008854:Microscopy, Electron; D008985:Monensin / Q000494:pharmacology; D012367:RNA, Viral / Q000032:analysis / Q000096:biosynthesis; D014158:Transcription, Genetic; D014415:Tunicamycin / Q000494:pharmacology; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects* / Q000235:genetics / Q000502:physiology / Q000648:ultrastructure; D015678:Viral Structural Proteins / Q000032:analysis / Q000096:biosynthesis; D014771:Virion / Q000187:drug effects / Q000235:genetics / Q000502:physiology / Q000648:ultrastructure; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D012367:RNA, Viral; D015678:Viral Structural Proteins; D014415:Tunicamycin; C041842:cicloxolone; D008985:Monensin; D002229:Carbenoxolone