title: Pyrosequencing allows the detection of emergent ganciclovir resistance mutations after HCMV infection.
abstract: Prenatally acquired human cytomegalovirus (HCMV) infection is the most frequent viral infection of newborns in developed countries. Virostatic therapy is accompanied by side effects and stepwise emergence of resistant virus variants. Different genotypic approaches show limited sensitivity in detecting on-growing minor resistant virus populations. Here, we demonstrate the superiority of pyrosequencing for the monitoring of mutant emergence. In a preterm baby born after 28 weeks of gestation and suffering from disseminated congenital HCMV infection, long-term control could not be achieved under ganciclovir/valganciclovir therapy and the infant died on the 113th day of life. Resistance-associated mutations in the HCMV UL97 gene were not detected by conventional DNA sequencing but postmortem pyrosequencing. Four different CMV variants carrying resistance-associated mutations each representing 11-17% of the total CMV population were found.
authors.affiliation: Department of Neonatology, Charité Universitätsmedizin, Berlin, Germany.
authors.forename: Susanne E
authors.initials: SE
authors.lastname: Kampmann
authors.forename: Birgit
authors.initials: B
authors.lastname: Schindele
authors.forename: Luise
authors.initials: L
authors.lastname: Apelt
authors.forename: Christoph
authors.initials: C
authors.lastname: Bührer
authors.forename: Lars
authors.initials: L
authors.lastname: Garten
authors.forename: Katharina
authors.initials: K
authors.lastname: Weizsaecker
authors.forename: Detlev H
authors.initials: DH
authors.lastname: Krüger
authors.forename: Bernhard
authors.initials: B
authors.lastname: Ehlers
authors.forename: Jörg
authors.initials: J
authors.lastname: Hofmann
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001344:Autopsy; D003587:Cytomegalovirus / Q000187:drug effects* / Q000235:genetics; D003586:Cytomegalovirus Infections / Q000188:drug therapy / Q000821:virology*; D004279:DNA, Viral / Q000235:genetics; D024882:Drug Resistance, Viral / Q000187:drug effects / Q000235:genetics*; D005260:Female; D015774:Ganciclovir / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000188:drug therapy / Q000821:virology*; D009154:Mutation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods; D017422:Sequence Analysis, DNA / Q000379:methods*
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D017853:Phosphotransferases (Alcohol Group Acceptor); C075365:ganciclovir kinase; D015774:Ganciclovir