Cytomegalovirus UL97 ganciclovir resistance mutations in kidney transplant recipients

Widespread and prolonged therapy with ganciclovir (GCV) may result in the emergence of GCV-resistant mutations in human cytomegalovirus (HCMV) genome. The aim of this study was to detect the UL97 mutations associated with GCV resistance in kidney transplant recipients.

Forty-nine kidney recipients with positive HCMV DNAemia, who received GCV therapy were included in this study. A 707 bp fragment of UL97 gene spanning codons (436 to 655) was amplified by nested PCR and sequenced.

Thirteen (26.5 %) out of 49 recipients contained mutations associated with amino acid changes. Two UL97 mutations related to GCV resistance were detected in 2 recipients (4 %), including alanine to valine (A594V) and proline to leucine (P521L). The D605E mutation was identified in 8 out of 49 (16.3 %) recipients. Silent mutations G598G, G503G, L553L, L634L, D456D and G579G were commonly observed.

Our results indicate that mutations in the UL97 gene associated with GCV resistance may occur in 1 in 25 recipients treated with GCV. In addition, a higher mutation rate of D605E was detected in our recipients. This study provides the first evidence of the prevalence and pattern of GCV related mutations in Iranian Turkish recipients (Tab. 2, Fig. 1, Ref. 28).