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A Novel Mutation in the Ul54 Gene of Human Cytomegalovirus Isolates that Confers Resistance to Foscarnet
- Source :
- Antiviral Therapy, Antiviral Therapy, International Medical Press, 2006, 11 (4), pp.537-540
- Publication Year :
- 2005
- Publisher :
- SAGE Publications, 2005.
-
Abstract
- International audience; 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.
- Subjects :
- Foscarnet
Human cytomegalovirus
viruses
Cytomegalovirus
DNA-Directed DNA Polymerase
Drug resistance
Recombinant virus
chemistry.chemical_compound
[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases
MESH: DNA-Directed DNA Polymerase
Pharmacology (medical)
Recombination, Genetic
[SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology
MESH: Microbial Sensitivity Tests
MESH: Drug Resistance, Viral
virus diseases
Infectious Diseases
[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology
Cytomegalovirus Infections
[SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases
MESH: Recombination, Genetic
MESH: Foscarnet
Cidofovir
medicine.drug
MESH: Antiviral Agents
Ganciclovir
MESH: Cytomegalovirus
MESH: Mutation
Microbial Sensitivity Tests
Biology
Antiviral Agents
Virus
Viral Proteins
Drug Resistance, Viral
medicine
Humans
Pharmacology
MESH: Humans
MESH: Cytomegalovirus Infections
Fibroblasts
biochemical phenomena, metabolism, and nutrition
medicine.disease
MESH: Viral Proteins
[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Virology
chemistry
MESH: Fibroblasts
Foscarnet Sodium
Mutation
[SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Subjects
Details
- ISSN :
- 20402058 and 13596535
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Antiviral Therapy
- Accession number :
- edsair.doi.dedup.....983e6c1fb5623dcb61f8b603c3b3d8ee