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Analysis of the UL97 Phosphotransferase Coding Sequence in Clinical Cytomegalovirus Isolates and Identification of Mutations Conferring Ganciclovir Resistance

Sunwen Chou, Alejo Erice, M. Colin Jordan, Gregory M. Vercellotti, Kendall R. Michels, Christine L. Talarico, Sylvia C. Stanat and Karen K. Biron
The Journal of Infectious Diseases
Vol. 171, No. 3 (Mar., 1995), pp. 576-583
Published by: Oxford University Press
Stable URL: http://www.jstor.org/stable/30134827
Page Count: 8
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Analysis of the UL97 Phosphotransferase Coding Sequence in Clinical Cytomegalovirus Isolates and Identification of Mutations Conferring Ganciclovir Resistance
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Abstract

The UL97 phosphotransferase coding sequences of clinical cytomegalovirus (CMV) isolates, 10 resistant and 11 sensitive to ganciclovir, were compared to define mutations associated with drug resistance. In each ganciclovir-resistant isolate, a mutation was found that resulted in an amino acid substitution at codon 460 (4 isolates), codon 594 (2 isolates), or codon 595 (4 isolates). No sensitive isolate carried any of these mutations. Marker transfer studies showed that each mutation was capable of conferring ganciclovir resistance to the laboratory CMV strain AD169. Rapid diagnostic tests based on DNA amplification and restriction enzyme analysis were developed for these mutations. Specific mutant DNAs were detected when they constituted at least 10% of the population in the specimen. Several mutations in UL97 appear to be common markers for ganciclovir resistance, and their detection may be a rapid alternative to conventional cell culture susceptibility testing.

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