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.
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 (less than 50 microM) the virus yield contained poor quality, non-infectious virus, but at higher CCX concentration (greater than or equal to 100 microM) 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 CCXs-1 [herpes simplex virus (HSV) type 1, HSV-2 and vesicular stomatitis virus], but essentially only (i) and (ii) affect Reo-3 (CCXs-2), whereas (i) and possibly (iii) affect Ad-5 (CCXs-2). In the case of SFV (CCXs-3) none of these mechanisms operate, but relocation of assembled virus is found.
Dargan
D J
DJ
MRC Virology Unit, University of Glasgow, U.K.
Galt
C B
CB
Subak-Sharpe
J H
JH
D000256:Adenoviridae / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002042:Bunyamwera virus / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D002229:Carbenoxolone / Q000031:analogs & derivatives* / Q000494:pharmacology; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D006056:Golgi Apparatus / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D012089:Mammalian orthoreovirus 3 / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D008854:Microscopy, Electron; D008985:Monensin / Q000494:pharmacology; D017955:Poliovirus / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D012672:Semliki forest virus / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; C041842:cicloxolone; D008985:Monensin; D002229:Carbenoxolone