Cytomegalovirus UL97 Mutations Affecting Cyclopropavir and Ganciclovir Susceptibility

Among the 7 most common UL97 mutations encountered in ganciclovir-resistant clinical cytomegalovirus isolates, the associated cyclopropavir cross-resistance varies from insignificant (L595S) to substantial (M460I and H520Q) as determined by recombinant phenotyping. Mutations M460I and H520Q were preferentially selected in vitro under cyclopropavir and conferred 12- to 20-fold increases in 50% effective concentration (EC(50)) values, while M460V, C592G, A594V, and C603W conferred 3- to 5-fold increases. Uncommon mutations M460T and C603R increased cyclopropavir EC(50)s by 8- to 10-fold.