Novel Cytomegalovirus UL54 DNA Polymerase Gene Mutations Selected In Vitro That Confer Brincidofovir Resistance

Eight in vitro selection experiments under brincidofovir pressure elicited the known cytomegalovirus DNA polymerase amino acid substitutions N408K and V812L and the novel exonuclease domain substitutions D413Y, E303D, and E303G, which conferred ganciclovir and cidofovir resistance with 6- to 11-fold...

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Bibliographic Details
Published in:Antimicrobial agents and chemotherapy 2016-06, Vol.60 (6), p.3845-3848
Main Authors: Chou, Sunwen, Ercolani, Ronald J, Lanier, E Randall
Format: Article
Language:English
Subjects:
Antiviral Agents
Antiviral Agents - pharmacology
Cidofovir
Cytomegalovirus
Cytomegalovirus - drug effects
Cytomegalovirus - genetics
Cytomegalovirus - growth & development
Cytomegalovirus - isolation & purification
Cytomegalovirus Infections - virology
Cytosine
Cytosine - analogs & derivatives
Cytosine - pharmacology
DNA-Directed DNA Polymerase
DNA-Directed DNA Polymerase - genetics
Drug Resistance, Viral - genetics
Foscarnet - pharmacology
Ganciclovir - pharmacology
Gene Expression
Humans
Microbial Sensitivity Tests
Mutation
Organophosphonates
Organophosphonates - pharmacology
Protein Domains
Viral Proteins
Viral Proteins - genetics
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Summary:Eight in vitro selection experiments under brincidofovir pressure elicited the known cytomegalovirus DNA polymerase amino acid substitutions N408K and V812L and the novel exonuclease domain substitutions D413Y, E303D, and E303G, which conferred ganciclovir and cidofovir resistance with 6- to 11-fold resistance to brincidofovir or 17-fold when E303G was combined with V812L. The new exonuclease domain I resistance mutations selected under brincidofovir pressure add to the single instance previously reported and show the expected patterns of cross-resistance.
ISSN:0066-4804
1098-6596
DOI:10.1128/AAC.00214-16