PMID: 8977495Dec 1, 1996Paper

Isolation of human adenovirus type 5 variants resistant to the antiviral cidofovir

Investigative Ophthalmology & Visual Science
Y J GordonPaul R Kinchington

Abstract

Cidofovir (S-HPMPC) is a potent broad-spectrum antiviral drug with potential clinical application against infections caused by human cytomegalovirus, herpes simplex virus, and adenovirus (AD). This study sought to determine whether variants of AD5 could be isolated in vitro that demonstrated increased resistance to this new antiviral drug. Homogenous stocks of wild-type AD5 (ATCC strain VR-5) were generated from isolated plaques grown in A549 cells. The stocks subsequently were serially passaged in cells containing increasing levels (from 5 to 75 micrograms/ml) of cidofovir. The recovered virus either was passaged, titrated, or assayed for 50% inhibitory concentration (IC50) of cidofovir. Three independently isolated variants were obtained that demonstrated increased resistance to cidofovir. Viral resistance to the drug increased on stepwise passage in higher concentrations. Compared to the ATCC AD5 reference (IC50 = 6.2 micrograms/ml), stable cidofovir-resistant variants showed fivefold to eightfold resistance (AD5 RI IC50 = 36.5 micrograms/ml; AD5 R2 IC50 = 36.7 micrograms/ml; and AD5 R3 IC50 = 32.6 micrograms/ml; analysis of variance, P = 0.000001). However, a variable number of passages (1 to 13) at each concentration of ci...Continue Reading

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