A novel mutation in the UL54 gene of human cytomegalovirus isolates that confers resistance to foscarnet.
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.
Ducancelle
Alexandra
A
Service de Bactériologie-Virologie, Hôpital Lariboisière, Assistance Publique-Hôpitaux de Paris, Paris, France.
Champier
Gaël
G
Alain
Sophie
S
Petit
Françoise
F
Le Pors
Marie-José Sanson
MJ
Mazeron
Marie-Christine
MC
D000998:Antiviral Agents / Q000494:pharmacology*; D003587:Cytomegalovirus / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D003586:Cytomegalovirus Infections / Q000821:virology; D004259:DNA-Directed DNA Polymerase / Q000235:genetics*; D024882:Drug Resistance, Viral / Q000235:genetics*; D005347:Fibroblasts / Q000821:virology; D017245:Foscarnet / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D009154:Mutation; D011995:Recombination, Genetic; D014764:Viral Proteins / Q000235:genetics*
D000998:Antiviral Agents; C109367:UL54 protein, Human herpesvirus 5; D014764:Viral Proteins; D017245:Foscarnet; D004259:DNA-Directed DNA Polymerase