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Fitness and virulence of a coxsackievirus mutant that can circumnavigate the need for phosphatidylinositol 4-kinase class III beta

By Hendrik Jan Thibaut, Hilde M van der Schaar, Kjerstin H W Lanke, Erik Verbeken, Martin Andrews, Pieter Leyssen, Johan Neyts and Frank J M van Kuppeveld


Coxsackieviruses require phosphatidylinositol-4-kinase IIIβ (PI4KIIIβ) for replication but can bypass this need by an H57Y mutation in protein 3A (3A-H57Y). We show that mutant coxsackievirus is not outcompeted by wild-type virus during 10 passages in vitro. In mice, the mutant virus proved as virulent as wild-type virus, even when mice were treated with a PI4KIIIβ inhibitor. Our data suggest that upon emergence, the 3A-H57Y mutant has the fitness to establish a resistant population with a virulence similar to that of wild-type virus

Topics: 1-Phosphatidylinositol 4-Kinase, Animals, Coxsackievirus Infections, Enterovirus, Genetic Fitness, Host-Pathogen Interactions, Mice, Mutation, Viral Proteins, Virulence, Virus Replication
Year: 2014
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