Novel mutation in the CMV UL97 gene associated with resistance to ganciclovir therapy

Cytomegalovirus (CMV) strains resistant to ganciclovir have been associated with specific mutations in the UL97 and UL54 genes. The UL97 gene of a CMV strain isolated from a renal transplant recipient before and after 438 day s of ganciclovir treatment was amplified by polymerase chain reaction and s equenced. A novel mutation resulting in deletion of codons 595 to 603 was i dentified in the viral DNA from specimens obtained after, but not before, p rolonged ganciclovir therapy. Clinical and virological resolution of CMV di sease occurred after switching to foscarnet therapy. Although many ganciclo vir resistance mutations have been mapped to the UL97 codon range 591-607, this one is unusual in that it involves deletion of half these codons. Beca use UL97 seems to be necessary for effective CMV replication, this deletion suggests that much of codons 591-607 can be removed without destroying the biological function of UL97, and that this codon range can be altered in v arious ways to affect ganciclovir susceptibility. Rapid, flexible genotypic assays directed at this part of UL97 may facilitate the early recognition of ganciclovir resistance.