A POINT MUTATION IN THE HUMAN CYTOMEGALOVIRUS UL97 GENE IS ASSOCIATEDWITH REDUCED SENSITIVITY TO GANCICLOVIR

The ganciclovir (GCV) resistance phenotype of human cytomegalovirus is olates is usually established by determination of 50 percent inhibitor y dose (ID50) values determined by plaque reduction assay. The sensiti vity index (ID50 of the isolate divided by ID50 of reference strain AD 169) is determined to reduce interassay variations of the ID50 values. The clinical significance of SI50 values remains unclear. The SI50 va lue of a strain recovered from a patient who was failing GCV-therapy, was 3. As resistance markers have recently been mapped within the cata lytic site of the UL97 kinase in some strains, this isolate was analys ed by sequencing the nucleotide sequence of the catalytic domain homol ogous region of UL97. This isolate contains a nucleotide change result ing to an amino acid substitution within the UL97 catalytic site. Amin oacid changes in this restricted region have been associated with clin ical 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 resist ance genotypic markers.