Key result
The 3A-H57Y mutant coxsackievirus demonstrated similar fitness in vitro and virulence in mice compared to wild-type virus, even during treatment with a PI4KIIIβ inhibitor.
The 3A-H57Y coxsackievirus mutant maintains fitness and virulence comparable to wild-type virus, allowing it to establish a resistant population.
Resistance to PI4KIIIβ inhibition may emerge without fitness cost; hypothesis-generating for antiviral durability in clinical enteroviral disease.
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.
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Thibaut et al. (2013) studied Coxsackievirus infection. 3A-H57Y mutant coxsackievirus vs. Wild-type coxsackievirus was evaluated on Fitness and virulence. The 3A-H57Y mutant coxsackievirus demonstrated similar fitness in vitro and virulence in mice compared to wild-type virus, even during treatment with a PI4KIIIβ inhibitor.
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