Dynamics of the Emergence of a Human Cytomegalovirus UL97 Mutant Strain Conferring Ganciclovir Resistance in a Pediatric Stem-Cell Transplant Recipient

Stem-cell transplant recipients are at risk of developing ganciclovir-resistant human cytomegalovirus (HCMV) infection caused by mutations in the viral UL97 gene. Knowledge of the relative proportions of coexisting HCMV wild-type and mutant strains may contribute to a better understanding of the dynamics of in vivo mutant strain selection under ganciclovir. Currently, genotype resistance screening for UL97 is routinely performed by restriction fragment length polymorphism detection and sequencing. We present here the longitudinal course of a pediatric recipient of an allogeneic stem-cell transplant infected with a ganciclovir-resistant HCMV strain. EDTA-treated blood samples were analyzed longitudinally. The patient acquired a primary HCMV infection shortly before transplantation and reactivated the virus following allogeneic hematopoietic stem cell transplantation, thus receiving an intensive antiviral treatment schedule. Three different methods for UL97 mutation analysis, restriction fragment length polymorphism detection, sequencing, and a new, real-time PCR approach were performed. In conclusion, for our pediatric patient, during peak viral load, the UL97 wild-type strain predominates, while during clinical deterioration with low viral load, the predominant mutant strain persists