title: Analysis of cytomegalovirus DNA polymerase (UL54) mutations in solid organ transplant patients receiving valganciclovir or ganciclovir prophylaxis.
abstract: We previously reported the absence of CMV UL97 (kinase) gene resistance mutations up to 12 months post-transplant following 100 days of valganciclovir prophylaxis, and a low incidence of resistance mutations following 100 days of oral ganciclovir prophylaxis in a prospective multicenter study in solid organ transplant recipients excluding lung transplants. Herein, we report UL54 (DNA polymerase) gene sequencing results for all patients with previous UL97 PCR-positive samples (n = 99) in our study. One UL54 resistance mutation (L545S known to confer ganciclovir and cidofovir resistance) was detected in a routine day-100 sample from an asymptomatic patient who received oral ganciclovir. Notably, this CMV UL54 mutation occurred in the absence of a UL97 mutation. Additionally, new UL54 variants were observed. Thus, emergence of CMV UL54 mutations in the absence of UL97 mutations is a rare but possible event that is not necessarily associated with detrimental clinical outcome in solid organ transplant recipients.
authors.affiliation: Research Center in Infectious Diseases, Centre Hospitalier Universitaire de Quebec and Laval University, Quebec City, Canada. Guy.Boivin@crchul.ulaval.ca
authors.forename: Guy
authors.initials: G
authors.lastname: Boivin
authors.forename: Nathalie
authors.initials: N
authors.lastname: Goyette
authors.forename: Christian
authors.initials: C
authors.lastname: Gilbert
authors.forename: Emma
authors.initials: E
authors.lastname: Covington
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018890:Chemoprevention; D003587:Cytomegalovirus / Q000201:enzymology* / Q000235:genetics; D003586:Cytomegalovirus Infections / Q000517:prevention & control / Q000821:virology; D004259:DNA-Directed DNA Polymerase / Q000235:genetics / Q000378:metabolism*; D024882:Drug Resistance, Viral / Q000235:genetics; D015774:Ganciclovir / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D015994:Incidence; D009154:Mutation; D016377:Organ Transplantation / Q000009:adverse effects*; D017422:Sequence Analysis, DNA; D000077562:Valganciclovir; 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; D000077562:Valganciclovir; D015774:Ganciclovir