A novel mutation in the UL54 gene of human cytomegalovirus isolates that confers resistance to foscarnet

• Published in: Antiviral therapy Vol. 11; no. 4; pp. 537 - 540
• Main Authors: DUCANCELLE, Alexandra, CHAMPIER, Gaël, ALAIN, Sophie, PETIT, Francoise, SANSON LE PORS, Marie-José, MAZERON, Marie-Christine
• Format: Journal Article
• Language: English
• Published: London International Medical Press 01.01.2006
• Subjects: Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral Agents; Antiviral Agents - pharmacology; Bacteriology; Biological and medical sciences; Cytomegalovirus; Cytomegalovirus - drug effects; Cytomegalovirus - genetics; Cytomegalovirus - growth & development; Cytomegalovirus Infections; Cytomegalovirus Infections - virology; DNA-Directed DNA Polymerase; DNA-Directed DNA Polymerase - genetics; Drug Resistance, Viral; Drug Resistance, Viral - genetics; Fibroblasts; Fibroblasts - virology; Foscarnet; Foscarnet - pharmacology; Human health and pathology; Humans; Infectious diseases; Life Sciences; Medical sciences; Microbial Sensitivity Tests; Microbiology and Parasitology; Mutation; Pharmacology. Drug treatments; Recombination, Genetic; Viral Proteins; Viral Proteins - genetics; Virology; Enzyme; Herpesviridae; Transferases; Foscarnet sodium; Enzyme inhibitor; Betaherpesvirinae; Human cytomegalovirus; Virus; Resistance; Nucleotidyltransferases; Gene; Antiviral; Isolate; Mutation
• ISSN: 1359-6535; 2040-2058
• DOI: 10.1177/135965350601100416

Foscarnet is currently licensed for the treatment of human cytomegalovirus (HCMV) infection. Mutations proven to confer resistance to foscarnet have mostly been mapped to regions II, III and VI of the HCMV UL54-encoded DNA polymerase. We previously showed that sequential foscarnet-resistant HCMV isolates recovered from a patient with lymphoma had change N495K in region delta-C of the DNA polymerase. To evaluate the impact of change N495K on HCMV sensitivity to foscarnet, a recombinant HCMV strain carrying the mutation was produced by homologous recombination. The recombinant virus showed a 3.4-fold increase in foscarnet resistance, and remained sensitive to ganciclovir and cidofovir. In addition, the recombinant strain showed a reduction of infectious virus yield compared with its parent strain. Change N495K should be added to the list of mutations conferring resistance to foscarnet and be taken into account in the genotypic diagnosis of antiviral resistance.