Mutations in the cytomegalovirus UL97 gene associated with ganciclovir-resistant retinitis.
Vitreous from patients with cytomegalovirus (CMV) retinitis was studied in order to identify mutations in the CMV UL97 gene associated with clinical resistance to ganciclovir. Point mutations known to confer resistance (V460, I460, V594, and S595) were found in 6 of 11 study eyes. Rapid genetic screening by restriction enzyme analysis of viral DNA amplified directly from the vitreous was as effective as conventional sequencing in detecting these mutations. Repeat biopsy of 3 eyes revealed no change in the UL97 genotype. The UL97 genotype differed between eyes in 2 of 3 patients with bilateral, clinically resistant CMV retinitis. In summary, resistance mutations of the CMV UL97 gene are found in the vitreous of some, but not all, eyes with CMV retinitis that have not responded to ganciclovir therapy. These mutations can differ between eyes in patients with bilateral disease and can be rapidly detected using restriction digest analysis of polymerase chain reaction-amplified viral DNA.
Liu
W
W
F. I. Proctor Foundation and the Department of Ophthalmology, University of California at San Francisco, 94143-0944, USA.
Kuppermann
B D
BD
Martin
D F
DF
Wolitz
R A
RA
Margolis
T P
TP
D017088:AIDS-Related Opportunistic Infections / Q000821:virology*; D019943:Amino Acid Substitution; D000998:Antiviral Agents / Q000627:therapeutic use*; D003001:Cloning, Molecular; D003587:Cytomegalovirus / Q000235:genetics*; D017726:Cytomegalovirus Retinitis / Q000188:drug therapy* / Q000209:etiology; D017931:DNA Primers; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification; D004352:Drug Resistance, Microbial; D015774:Ganciclovir / Q000627:therapeutic use*; D005814:Genes, Viral; D005838:Genotype; D006801:Humans; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics*; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D015183:Restriction Mapping; D015678:Viral Structural Proteins / Q000235:genetics*; D014822:Vitreous Body / Q000821:virology
D000998:Antiviral Agents; D017931:DNA Primers; D004279:DNA, Viral; D015678:Viral Structural Proteins; D017853:Phosphotransferases (Alcohol Group Acceptor); C075365:ganciclovir kinase; D015774:Ganciclovir