title: Novel DNA polymerase mutations conferring cytomegalovirus resistance: input of BAC-recombinant phenotyping and 3D model.
abstract: Long-term exposure to antiviral therapy in immunocompromised patients favors emergence of human cytomegalovirus (HCMV) resistance mutations. Two new UL54 DNA polymerase mutations (deletion of codon 524 and N408S substitution) identified in a kidney recipient and a bone marrow recipient respectively were characterized. Marker transfer experiment through recombination into a HCMV AD169 BAC demonstrated del524 and mutation N408S confer GCV and CDV resistance. These results suggest continued mutation of UL54 under selective antiviral pressure. Characterization of each new mutation is thus required to inform genotypic assays and to better understand the functional regions of UL54 for the development of novel antivirals.
authors: UMR-S1092, Univ. Limoges, 87000 Limoges, France.
authors: Sébastien
authors: S
authors: Hantz
authors: Sébastien
authors: S
authors: Cotin
authors: Eva
authors: E
authors: Borst
authors: Anthony
authors: A
authors: Couvreux
authors: Arielle
authors: A
authors: Salmier
authors: Isabelle
authors: I
authors: Garrigue
authors: Pierre
authors: P
authors: Merville
authors: Catherine
authors: C
authors: Mengelle
authors: Michel
authors: M
authors: Attal
authors: Martin
authors: M
authors: Messerle
authors: Sophie
authors: S
authors: Alain
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics / Q000378:metabolism; D003587:Cytomegalovirus / Q000187:drug effects* / Q000201:enzymology* / Q000235:genetics; D003586:Cytomegalovirus Infections / Q000188:drug therapy* / Q000209:etiology / Q000821:virology; D004259:DNA-Directed DNA Polymerase / Q000235:genetics* / Q000378:metabolism; D024882:Drug Resistance, Viral; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects; D008958:Models, Molecular; D009154:Mutation; D010641:Phenotype; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; C109367:UL54 protein, Human herpesvirus 5; D014764:Viral Proteins; D004259:DNA-Directed DNA Polymerase