title: Genotypic characterization of human cytomegalovirus UL97 phosphotransferase natural polymorphism in the era of ganciclovir and maribavir.
abstract: The molecular mechanisms of human cytomegalovirus (CMV) resistance to both ganciclovir and maribavir reported so far rely predominantly on the presence of mutations within UL97 phosphotransferase. The accurate interpretation of genotypic antiviral resistance assay results requires the clear distinction between resistance mutations and natural interstrain sequence variations. The objective of this work was to extend the catalog of CMV UL97 phosphotransferase natural polymorphisms. The full-length UL97 gene sequence analysis from 4 laboratory strains and 35 clinical samples from patients who had not received any previous anti-CMV treatment was performed. At the nucleotide level, the interstrain identity was >98%. At the amino acid level, ten natural polymorphisms never previously described were identified. Together with all previous results reported in the literature, a new map of UL97 phosphotransferase natural polymorphism could be settled in the era of ganciclovir and maribavir.
authors.affiliation: UPMC Univ Paris, ER1 DETIV, France. david.boutolleau@psl.aphp.fr
authors.forename: David
authors.initials: D
authors.lastname: Boutolleau
authors.forename: Sonia
authors.initials: S
authors.lastname: Burrel
authors.forename: Henri
authors.initials: H
authors.lastname: Agut
mesh_terms: D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001483:Base Sequence; D001562:Benzimidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D003587:Cytomegalovirus / Q000187:drug effects / Q000235:genetics*; D003586:Cytomegalovirus Infections / Q000188:drug therapy; D024882:Drug Resistance, Viral / Q000187:drug effects*; D015774:Ganciclovir / Q000494:pharmacology* / Q000627:therapeutic use; D005838:Genotype; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000737:chemistry / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012263:Ribonucleosides / Q000494:pharmacology* / Q000627:therapeutic use; D017422:Sequence Analysis, DNA; D004004:Dichlororibofuranosylbenzimidazole / Q000031:analogs & derivatives
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles; D015774:Ganciclovir; D017853:Phosphotransferases (Alcohol Group Acceptor); D012263:Ribonucleosides; C075365:ganciclovir kinase; C400401:maribavir; D004004:Dichlororibofuranosylbenzimidazole