Contrasting effect of new HCMV pUL54 mutations on antiviral drug susceptibility: Benefits and limits of 3D analysis.
Antiviral Res
; 129: 115-119, 2016 May.
Article
en En
| MEDLINE
| ID: mdl-26872863
ABSTRACT
Human cytomegalovirus (HCMV) resistance to antiviral drugs is a major drawback of repeated or long-duration treatment in immunocompromised patients. Resistance testing is usually performed by genotypic assays. For accurate interpretation of these assays, the role of new mutations in HCMV resistance has to be assessed. Two previously unknown UL54 single point mutations (D515Y and V787A) were characterized for phenotypic drug-resistance by marker transfer analysis using bacterial artificial chromosome (BAC) mutagenesis. Increases in 50% inhibitory concentrations of ganciclovir and foscarnet were found for both mutated recombinant strains showing that mutations D515Y and V787A induce resistance to both antivirals. Importantly, none of those impacted the viral growth kinetics. For a better understanding of their molecular resistance mechanisms, a 3D homology model was used to localize the mutated amino-acids in functional domains of UL54 and predict their impact on UL54 function and resistance. However, 3D homology model analysis has limits and phenotypic characterization using BAC-HCMV is still essential to measure the role of unknown mutations.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Antivirales
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Proteínas Virales
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Modelos Moleculares
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Mutación Puntual
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Citomegalovirus
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Farmacorresistencia Viral
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ADN Polimerasa Dirigida por ADN
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Año:
2016
Tipo del documento:
Article