MUTATIONS IN THE CYTOMEGALOVIRUS UL97 GENE ASSOCIATED WITH GANCICLOVIR-RESISTANT RETINITIS

Vitreous from patients with cytomegalovirus (CMV) retinitis was studie d in order to identify mutations in the CMV UL97 gene associated with clinical resistance to ganciclovir. Point mutations known to confer re sistance (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 revea led no change in the UL97 genotype. The UL97 genotype differed between eyes in 2 of 3 patients with bilateral, clinically resistant CMV reti nitis. In summary, resistance mutations of the CMV UL97 gene are found in the vitreous of some, but not all, eyes with CR IV retinitis that have not responded to ganciclovir therapy. These mutations can differ between eyes in patients with bilateral disease and can be rapidly det ected using restriction digest analysis of polymerase chain reaction-a mplified viral DNA.