The difference in sensitivity to cicloxolone sodium between herpes simplex virus types 1 and 2 maps to the locations of genes UL22 (gH) and UL44 (gC).
Cicloxolone sodium (CCX) is a broad spectrum antiviral agent which has a largely non-specific and complex mode of antiviral action. However, the experimental finding that herpes simplex virus type 2 (HSV-2) (strain HG52) is consistently more sensitive to inhibition by CCX than HSV-1 (117 syn+) additionally implies the specific involvement of HSV genes. HSV-1/HSV-2 intertypic recombinants have been utilized to investigate this genetic difference by comparing their CCX ED50 concentrations. No short stretch of HSV-2 DNA was associated with its greater sensitivity to CCX, implying that two or more non-contiguously located HSV genes are involved. Correlating CCX sensitivity with recombinant virus genome structures allowed separate evaluation of the gene regions encoding glycoproteins gB, gC, gD, gE, gG, gH and gI and this suggests that the gene locations encoding gH and gC determine the CCX sensitivity difference. The selective inhibitor of Golgi apparatus glycosylation, monensin, gave results analogous to those obtained with CCX.
Dargan
D J
DJ
MRC Virology Unit, Institute of Virology, University of Glasgow, U.K.
Subak-Sharpe
J H
JH
D000998:Antiviral Agents / Q000494:pharmacology*; D002229:Carbenoxolone / Q000031:analogs & derivatives* / Q000494:pharmacology; D002460:Cell Line; D002874:Chromosome Mapping; D004305:Dose-Response Relationship, Drug; D004352:Drug Resistance, Microbial / Q000235:genetics; D005814:Genes, Viral; D006801:Humans; D012703:Serotyping; D018139:Simplexvirus / Q000145:classification / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development; D014759:Viral Envelope Proteins / Q000235:genetics*
D000998:Antiviral Agents; D014759:Viral Envelope Proteins; C048232:glycoprotein C, herpes simplex virus type 2; C044200:glycoprotein H, herpes simplex virus type 1; C041842:cicloxolone; D002229:Carbenoxolone