A point mutation in the human cytomegalovirus UL97 gene is associated with reduced sensitivity to ganciclovir

The ganciclovir (GCV) resistance phenotype of human cytomegalovirus isolates is usually established by determination of 50 percent inhibitory dose (ID50) values determined by plaque reduction assay. The sensitivity index (ID50 of the isolate divided by ID50 of reference strain AD169) is determined to reduce interassay variations of the ID50 values. The clinical significance of SI50 values remains unclear. The SI50 value of a strain recovered from a patient who was failing GCV-therapy, was 3. As resistance markers have recently been mapped within the catalytic site of the UL97 kinase in some strains, this isolate was analysed by sequencing the nucleotide sequence of the catalytic domain homologous region of UL97. This isolate contains a nucleotide change resulting to an amino acid substitution within the UL97 catalytic site. Aminoacid changes in this restricted region have been associated with clinical resistance in vivo. These results point out that isolates with a GCV SI50 value close to 3, can be associated in vivo with sensitivity or resistance and should be studied further for the presence of resistance genotypic markers.