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Mutation in Region III of the DNA Polymerase Gene Conferring Foscarnet Resistance in Cytomegalovirus Isolates from 3 Subjects Receiving Prolonged Antiviral Therapy

Sunwen Chou, Gail Marousek, David M. Parenti, Shelley M. Gordon, Alison G. LaVoy, Jennifer G. Ross, Richard C. Miner and W. Lawrence Drew
The Journal of Infectious Diseases
Vol. 178, No. 2 (Aug., 1998), pp. 526-530
Published by: Oxford University Press
Stable URL: http://www.jstor.org/stable/30119571
Page Count: 5
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Mutation in Region III of the DNA Polymerase Gene Conferring Foscarnet Resistance in Cytomegalovirus Isolates from 3 Subjects Receiving Prolonged Antiviral Therapy
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Abstract

Three human immunodeficiency virus-infected subjects with progressive cytomegalovirus (CMV) retinitis despite prolonged antiviral therapy had buffy coat CMV isolates that were resistant to both ganciclovir and foscarnet. Genetic analysis of the resistant isolates showed that each contained a well-known ganciclovir resistance mutation in the viral UL97 phosphotransferase sequence, as well as a mutation (Ala to Val at codon 809, V809) in conserved region III of the DNA polymerase (Pol) sequence. A segment of the Pol sequence from one of the clinical isolates was transferred to CMV laboratory strain AD169 by homologous recombination. The recombinant virus containing V809 showed 6.3-fold increased foscarnet resistance and 2.6-fold increased ganciclovir resistance. Occurrence of the V809 mutation in 3 unrelated cases suggests that it is a clinically significant viral genetic marker for foscarnet resistance and decreased susceptibility to ganciclovir.

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