ArticleAntimicrobial agents and chemotherapy2007
Multidrug resistance conferred by novel DNA polymerase mutations in human cytomegalovirus isolates.
Article in Antimicrobial agents and chemotherapy, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 86 citations in OpenAlex.
- A TRUSTED targeted mass spectrometry assay for pan-herpesvirus protein detection.Cell reports · 2022Article
- Opposite effects of cytomegalovirus UL54 exonuclease domain mutations on acyclovir and cidofovir susceptibility.Antiviral research · 2021Article
- Investigational Antiviral Therapy Models for the Prevention and Treatment of Congenital Cytomegalovirus Infection during Pregnancy.Antimicrobial agents and chemotherapy · 2020Article
- Advances in the genotypic diagnosis of cytomegalovirus antiviral drug resistance.Antiviral research · 2020Review
- Whole-Genome Approach to Assessing Human Cytomegalovirus Dynamics in Transplant Patients Undergoing Antiviral Therapy.Frontiers in cellular and infection microbiology · 2020Article
- Case Report: Management of a Multidrug-Resistant CMV-Strain in a Renal Transplant Recipient by High-Dose CMV-Specific Immunoglobulins, Modulation in Immunosuppression, and Induction of CMV-Specific Cellular Immunity.Frontiers in immunology · 2020Article
- Article
- Distribution and effects of amino acid changes in drug-resistant α and β herpesviruses DNA polymerase.Nucleic acids research · 2016Review
- Antiviral Drug- and Multidrug Resistance in Cytomegalovirus Infected SCT Patients.Computational and structural biotechnology journal · 2015Review
- Characterization of multiple cytomegalovirus drug resistance mutations detected in a hematopoietic stem cell transplant recipient by recombinant phenotyping.Journal of clinical microbiology · 2014Article
- Foscarnet-resistant cytomegalovirus esophagitis with stricturing.Case reports in gastroenterology · 2013Article
- Cyclopropavir susceptibility of cytomegalovirus DNA polymerase mutants selected after antiviral drug exposure.Antimicrobial agents and chemotherapy · 2012Article
- The genetic basis of human cytomegalovirus resistance and current trends in antiviral resistance analysis.Infectious disorders drug targets · 2011Review
- The novel anticytomegalovirus compound AIC246 (Letermovir) inhibits human cytomegalovirus replication through a specific antiviral mechanism that involves the viral terminase.Journal of virology · 2011Article
- Recombinant phenotyping of cytomegalovirus UL54 mutations that emerged during cell passages in the presence of either ganciclovir or foscarnet.Antimicrobial agents and chemotherapy · 2011Article
- Phosphonoformic acid inhibits viral replication by trapping the closed form of the DNA polymerase.The Journal of biological chemistry · 2011Article
- Human cytomegalovirus kinetics following institution of artesunate after hematopoietic stem cell transplantation.Antiviral research · 2011Article
- The search for new therapies for human cytomegalovirus infections.Virus research · 2011Review
- Phenotypic diversity of cytomegalovirus DNA polymerase gene variants observed after antiviral therapy.Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology · 2011Article
- Differentiation between polymorphisms and resistance-associated mutations in human cytomegalovirus DNA polymerase.Antimicrobial agents and chemotherapy · 2010Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
The emergence of antiviral-resistant cytomegalovirus (CMV) strains is a continuing clinical problem, with increased numbers of immunocompromised patients given longer-duration antiviral prophylaxis. Two previously unrecognized CMV DNA polymerase mutations (N408K and A834P) identified separately and together in at-risk lung and kidney transplant recipients and a third mutation (L737M) identified in a liver transplant recipient were characterized by marker transfer to antiviral-sensitive laboratory strains AD169 and Towne. Subsequent phenotypic analyses of recombinant strains demonstrated the ability of mutation N408K to confer ganciclovir (GCV) and cidofovir (CDV) resistance and of mutation A834P to confer GCV, foscarnet, and CDV resistance. Mutation L737M did not confer resistance to any of the antiviral agents tested. A recombinant strain containing both N408K and A834P demonstrated increased GCV and CDV resistance compared to the levels of resistance of the virus containing only the A834P mutation. The addition of mutation N408K in combination with A834P also partially reconstituted the replication impairment of recombinant virus containing only A834P. This suggests that perturbation of both DNA polymerization (A834P) and exonuclease (N408K) activities contributes to antiviral resistance and altered replication kinetics in these mutant strains. The identification of these multidrug-resistant CMV strains in at-risk seronegative recipients of organs from seropositive donors suggests that improved prophylactic and treatment strategies are required. The additive effect of multiple mutations on antiviral susceptibility suggests that increasing antiviral-resistant phenotypes can result from different virus-antiviral interactions.
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