Susceptibilities of herpes simplex viruses to penciclovir and acyclovir in eight cell lines.
The commonly used antiviral drugs acyclovir (ACV) and penciclovir (PCV) possess similarly potent antiviral activities in vivo against herpes simplex virus (HSV). Assay methods for sensitivity to ACV are not necessarily transferable to PCV, even though the two drugs have similar in vivo potencies and mechanisms of action. We determined by plaque reduction assay the relative activities of ACV and PCV against five laboratory-adapted strains of HSV types 1 and 2 (including sensitive and resistant strains) in seven human cell lines and one nonhuman primate cell line. Seven characteristics were used to evaluate the cell lines. All cell lines were similar in their plating efficiencies and abilities to discriminate between sensitive and resistant HSV isolates. Vero and MRC-5 cells yielded the most discordant 50% inhibitory concentrations (IC50s) for the two HSV types, while Vero and WI-38 VA-13 cells yielded large differences in the IC50s of ACV and PCV. The limited life spans and poor plaque morphologies of the fibroblast lines were undesirable characteristics. Among the transformed cell lines producing well-defined plaques, A549 cells provided the best concordance between IC50s for the two HSV types and two antiherpes drugs. Comparison experiments with a yield reduction format indicated that the use of assays of this type might allow some of the cell-specific properties observed in plaque reduction assays to be avoided.
Leary
Jeffry J
JJ
GlaxoSmithKline, The Antimicrobial and Host Defense Center of Excellence for Drug Discovery, Department of Host Defense, Collegeville, Pennsylvania, USA. jjl27773@glaxowellcome.com
Wittrock
Robert
R
Sarisky
Robert T
RT
Weinberg
Adriana
A
Levin
Myron J
MJ
D000212:Acyclovir / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D005838:Genotype; D006147:Guanine; D006801:Humans; D010641:Phenotype; D010766:Phosphorylation; D018139:Simplexvirus / Q000187:drug effects* / Q000235:genetics; D010948:Viral Plaque Assay
D000998:Antiviral Agents; C053539:penciclovir; D006147:Guanine; D000212:Acyclovir