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.
Division of Infectious Diseases, Oregon Health and Science University, Portland, OR, USA. chous@ohsu.edu
Sunwen
S
Chou
Terry L
TL
Bowlin
D000998:Antiviral Agents / Q000494:pharmacology*; D003521:Cyclopropanes / Q000494:pharmacology*; D003587:Cytomegalovirus / Q000187:drug effects* / Q000235:genetics; D024882:Drug Resistance, Viral / Q000235:genetics; D015774:Ganciclovir / Q000494:pharmacology*; D005838:Genotype; D006147:Guanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009154:Mutation; D010641:Phenotype
D000998:Antiviral Agents; D003521:Cyclopropanes; D006147:Guanine; C495219:cyclopropavir; D015774:Ganciclovir