1887

Journal of General Virology header logo

Volume 73, Issue 2

The effect of cicloxolone sodium on the replication in cultured cells of adenovirus type 5, reovirus type 3, poliovirus type 1, two bunyaviruses and Semliki Forest virus Free

Abstract

The effect of cicloxolone sodium (CCX) on the replication of typical representatives of different virus families [adenovirus type 5 (Ad-5), reovirus type 3 (Reo-3), Bunyamwera and Germiston viruses, poliovirus type 1 (Polio-1) and Semliki Forest virus (SFV)] in tissue culture was investigated. The Golgi apparatus inhibitor monensin (Mon) and CCX were shown to have analogous effects on some aspects of virus replication. Although the Mon-like effect of CCX played no role in the antiviral activity against Ad-5, Reo-3 or Polio-1, it could entirely account for the antiviral activity against the Bunyamwera and Germiston viruses, for which inhibition of glycoprotein processing was responsible for the antiviral activity. In the case of SFV, the Mon-like activity of CCX caused cytoplasmic assembly of fully infectious SFV within vacuoles and thus impaired virus release without altering total infectious virus yield. Fewer Ad-5 and Reo-3 progeny were produced in the presence of the drug. CCX had a dose-dependent biphasic effect on the particle:p.f.u. ratio of the Reo-3 yield. At low CCX concentration (<50 µ) the virus yield contained poor quality, non-infectious virus, but at higher CCX concentration (⩾ 100 µ) low quality virus could no longer be successfully assembled. We conclude that the antiviral effect can be manifested in three ways: (i) by a reduction in the virus particle yield produced; (ii) by a loss of quality (relative infectivity); (iii) by a virucidal effect of the drug. We have previously defined three CCX sensitivity classes. Mechanisms (i), (ii) and (iii) operate against viruses belonging to class CCX-1 [herpes simplex virus (HSV) type 1, HSV-2 and vesicular stomatitis virus], but essentially only (i) and (ii) affect Reo-3 (CCX-2), whereas (i) and possibly (iii) affect Ad-5 (CCX-2). In the case of SFV (CCX-3) none of these mechanisms operate, but relocation of assembled virus is found.

  • Received:
  • Accepted:
  • Published Online:
© Journal of General Virology 1992
Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-73-2-407
1992-02-01
2024-04-19
Loading full text...

Full text loading...

/deliver/fulltext/jgv/73/2/JV0730020407.html?itemId=/content/journal/jgv/10.1099/0022-1317-73-2-407&mimeType=html&fmt=ahah

References

  1. Dargan D. J., Subak-Sharpe J. H. 1985; The effect of triterpenoid compounds on uninfected and herpes simplex virus-infected cells in culture. I. Effect on cell growth, virus particles and virus replication. Journal of General Virology 66:1771–1784
     [Google Scholar]
  2. Dargan D. J., Subak-Sharpe J. H. 1986; The effect of triterpenoid compounds on uninfected and herpes simplex virus-infected cells in culture. II. DNA and protein synthesis, polypeptide processing and transport. Journal of General Virology 67:1831–1850
     [Google Scholar]
  3. Dargan D. J., Subak-Sharpe J. H. 1991; The difference in sensitivity to cicloxolone sodium between herpes simplex virus types 1 and 2 maps to the locations of genes UL22 (g H) and UL44 (g C). Journal of General Virology 72:377–384
     [Google Scholar]
  4. Dargan D. J., Aitken J. D., Subak-Sharpe J. H. 1988; The effect of triterpenoid compounds on uninfected and herpes simplex virus-infected cells in culture. III. Ultrastructural study of virion maturation. Journal of General Virology 69:439–444
     [Google Scholar]
  5. Dargan D. J., Galt C. B., Subak-Sharpe J. H. 1992; The effect of cicloxolone sodium on the replication of vesicular stomatitis virus in BSC-1 cells. Journal of General Virology 73:397–406
     [Google Scholar]
  6. Galt C., Dargan D. J., Subak-Sharpe J. H. 1990; In vitro studies of the antiviral range of cicloxolone sodium and identification of cell lines tolerant to the drug. Antiviral Chemistry and Chemotherapy 1:115–123
     [Google Scholar]
  7. Griffiths G., Quinn P., Warren G. 1983; Dissection of the Golgi complex. 1. Monensin inhibits the transport of viral membrane proteins from medial to trans Golgi cisternae in baby hamster kidney cells infected with Semliki Forest virus. Journal of Cell Biology 96:835–850
     [Google Scholar]
  8. Hakimi J., Atkinson P. H. 1982; Glycosylation of intracellular Sindbis virus glycoproteins. Biochemistry 21:2140–2195
     [Google Scholar]
  9. Marsden H. S., Crombie I. K., Subak-Sharpe J. H. 1976; Control of protein synthesis in herpesvirus-infected cells: analysis of the polypeptides induced by wild type and sixteen temperature-sensitive mutants of HSV strain 17. Journal of General Virology 31:347–372
     [Google Scholar]
  10. Melancon P., Garoff H. 1987; Processing of the Semliki Forest virus structural polyprotein: role of the capsid protease. Journal of Virology 61:1301–1309
     [Google Scholar]
  11. Simons K., Garoff H. 1980; The budding mechanisms of enveloped animal viruses. Journal of General Virology 50:1–21
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-73-2-407
Loading
The effect of cicloxolone sodium on the replication in cultured cells of adenovirus type 5, reovirus type 3, poliovirus type 1, two bunyaviruses and Semliki Forest virus
J. Gen. Virol. 73, 407 (1992); https://doi.org/10.1099/0022-1317-73-2-407
/content/journal/jgv/10.1099/0022-1317-73-2-407
/content/journal/jgv/10.1099/0022-1317-73-2-407
Loading

Data & Media loading...

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error