Patient-Derived Cytomegaloviruses with Different Ganciclovir Sensitivities from UL97 Mutation Retain Their Replication Efficiency and Some Kinase Activity In Vitro

Mutations in the cytomegalovirus UL97 kinase gene contribute to antiviral resistance. Mutations A594S and G598D from two clinical isolates were analyzed, and bacterial artificial chromosome (BAC)-engineered A594S recombinant cytomegalovirus exhibited a ganciclovir-resistant phenotype on plaque reduc...

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Bibliographic Details
Published in:Antimicrobial agents and chemotherapy 2019-09, Vol.63 (9)
Main Authors: Wong, Diana D, van Zuylen, Wendy J, Hamilton, Stuart T, Steingruber, Mirjam, Sonntag, Eric, Marschall, Manfred, Rawlinson, William D
Format: Article
Language:English
Subjects:
Antiviral Agents
Cytomegalovirus
Ganciclovir
Protein Kinases
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Summary:Mutations in the cytomegalovirus UL97 kinase gene contribute to antiviral resistance. Mutations A594S and G598D from two clinical isolates were analyzed, and bacterial artificial chromosome (BAC)-engineered A594S recombinant cytomegalovirus exhibited a ganciclovir-resistant phenotype on plaque reduction. Viral replication was comparable to that of the wild type. Cell-based kinase activity and autophosphorylation of ectopically expressed proteins showed that mutants retained some kinase activity. This study showed that patient-derived cytomegalovirus with different ganciclovir sensitivities retained replication efficiency and exhibited some kinase activity .
ISSN:0066-4804
1098-6596
DOI:10.1128/AAC.02425-18