Genetic variability of cytomegalovirus glycoprotein O in hematopoietic stem cell transplant recipients

Abstract

Genetic variation of cytomegalovirus (CMV) strains can correlate with their pathogenicity for immunocompromised patients. Glycoprotein O (gO), together with glycoprotein L and glycoprotein H, mediate the fusion of the viral envelope with the cell membrane and promotes virus penetration, envelopment, and release. The variability of gO might play a role in CMV cell tropism. The goal was a retrospective analysis of gO variability in a cohort of hematopoietic stem cell transplant (HSCT) recipients to determine the distribution of gO genotypes and to investigate their impact on clinical outcome and manifestation of CMV infection. In archived blood samples from 51 adult allogeneic HSCT recipients with active CMV infection, gO was analyzed by sequencing the N-terminal domain of the UL74 gene using the dye deoxy termination method. The gO1 and gO2 clades were most common (39% and 20%, respectively, and gO3 was associated with higher risk of symptomatic infection (P = 0.026 in multivariant analysis). Despite being associated with higher antigenemia levels (P = 0.02), gO4 had the best survival and lower rate of CMV recurrence. No significant differences were found in clinical manifestation and outcome of CMV disease between patients with various gO clades. Because CMV strains sharing an identical gO sequence differed in glycoprotein B genotypes, sequencing the N-terminal part of the gO gene does not seem to be optimal for the identification of strains. gO genotyping may contribute to the biological characterization of CMV strains in HSCT recipients.