Cytomegalovirus UL97 Kinase Catalytic Domain Mutations That Confer Multidrug Resistance

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Cytomegalovirus UL97 kinase catalytic domain mutations that confer multidrug resistance.

Human cytomegalovirus UL97 kinase mutations that commonly confer ganciclovir resistance cluster in different parts of the gene than those conferring resistance to maribavir, an experimental UL97 kinase inhibitor. The drug resistance, growth, and autophosphorylation phenotypes of several unusual UL97 mutations in the kinase catalytic domain were characterized. Mutations V466G and P521L, describe...

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The cytomegalovirus (CMV) UL97 kinase inhibitor maribavir (MBV) is undergoing clinical antiviral trials. Two clinical CMV isolates serially passaged in cell culture under MBV showed >20-fold increases in MBV resistance after the development of the UL97 mutation V353A in one of the isolates and of T409M in the other. Marker transfer studies confirmed that the V353A and T409M mutations conferred ...

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ژورنال

عنوان ژورنال: Antimicrobial Agents and Chemotherapy

سال: 2013

ISSN: 0066-4804,1098-6596

DOI: 10.1128/aac.00511-13