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

Thibaut, Hendrik Jan; van der Schaar, Hilde M; Lanke, Kjerstin HW; Verbeken, Erik; Andrews, Martin; Leyssen, Pieter; Neyts, Johan; van Kuppeveld, Frank JM

doi:10.1128/JVI.03177-13

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

Author:

Thibaut, Hendrik Jan

van der Schaar, Hilde M ; Lanke, Kjerstin HW ; Verbeken, Erik ; Andrews, Martin ; Leyssen, Pieter ; Neyts, Johan ; van Kuppeveld, Frank JM

Keywords:

Science & Technology, Life Sciences & Biomedicine, Virology, ENTEROVIRUS REPLICATION, B4-INDUCED PANCREATITIS, ENVIROXIME, RESISTANCE, INHIBITOR, COMPOUND, TARGETS, MODEL, 1-Phosphatidylinositol 4-Kinase, Animals, Coxsackievirus Infections, Enterovirus, Genetic Fitness, Host-Pathogen Interactions, Mice, Mutation, Viral Proteins, Virulence, Virus Replication, 06 Biological Sciences, 07 Agricultural and Veterinary Sciences, 11 Medical and Health Sciences, 30 Agricultural, veterinary and food sciences, 31 Biological sciences, 32 Biomedical and clinical sciences

Abstract:

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.