title: Multiple ganciclovir-resistant strains in a newborn with symptomatic congenital human cytomegalovirus infection.
abstract: A case of human cytomegalovirus (HCMV) drug-resistance in a congenitally infected newborn is described. Unusual aspects of this case include: (i) the detection of an extremely complex virus population, composed of a mixture of wild-type (wt) and multiple mutant ganciclovir (GCV) and valganciclovir (val-GCV) resistant strains carrying a variety of known mutations in UL97; (ii) the identification of novel UL97 mutations and (iii) the first time detection of combined UL97 drug resistance mutations in the same viral strain. In detail, four known UL97 single-nucleotide mutations (A594T/V, M460V/I, C592G), a new amino-acid substitution (C607S), and a new deletion (597-600) in one of the three UL97 hot spots for GCV/val-GCV resistance (codons 460, 520 and 590-607) were detected. In addition, the combination of M460V+A594V and M460V+C592G was observed for the first time. The emergence of HCMV drug-resistance in symptomatic congenital infections chronically treated with GCV or val-GCV should be taken into account. The immaturity of the neonatal immune system may contribute to selection of complex virus populations in these patients.
authors.affiliation: Molecular Virology Unit, Virology and Microbiology Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Campanini
authors.forename: Maurizio
authors.initials: M
authors.lastname: Zavattoni
authors.forename: Emilio
authors.initials: E
authors.lastname: Cristina
authors.forename: Diego
authors.initials: D
authors.lastname: Gazzolo
authors.forename: Mauro
authors.initials: M
authors.lastname: Stronati
authors.forename: Fausto
authors.initials: F
authors.lastname: Baldanti
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D000998:Antiviral Agents / Q000494:pharmacology*; D060085:Coinfection / Q000821:virology; D003587:Cytomegalovirus / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D003586:Cytomegalovirus Infections / Q000151:congenital* / Q000821:virology*; D004279:DNA, Viral / Q000235:genetics; D024882:Drug Resistance, Viral; D005260:Female; D015774:Ganciclovir / Q000494:pharmacology*; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D020125:Mutation, Missense; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics; D011247:Pregnancy
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D017853:Phosphotransferases (Alcohol Group Acceptor); C075365:ganciclovir kinase; D015774:Ganciclovir