title: Fitness and virulence of a coxsackievirus mutant that can circumnavigate the need for phosphatidylinositol 4-kinase class III beta.
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.
authors.affiliation: Department of Infectious Diseases & Immunology, Virology Division, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
authors.forename: Hendrik Jan
authors.initials: HJ
authors.lastname: Thibaut
authors.forename: Hilde M
authors.initials: HM
authors.lastname: van der Schaar
authors.forename: Kjerstin H W
authors.initials: KH
authors.lastname: Lanke
authors.forename: Erik
authors.initials: E
authors.lastname: Verbeken
authors.forename: Martin
authors.initials: M
authors.lastname: Andrews
authors.forename: Pieter
authors.initials: P
authors.lastname: Leyssen
authors.forename: Johan
authors.initials: J
authors.lastname: Neyts
authors.forename: Frank J M
authors.initials: FJ
authors.lastname: van Kuppeveld
mesh_terms: D019870:1-Phosphatidylinositol 4-Kinase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D003384:Coxsackievirus Infections / Q000378:metabolism / Q000821:virology; D004770:Enterovirus / Q000472:pathogenicity / Q000502:physiology*; D056084:Genetic Fitness; D054884:Host-Pathogen Interactions; D051379:Mice; D009154:Mutation; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D014774:Virulence / Q000235:genetics; D014779:Virus Replication
chemical_list: D014764:Viral Proteins; D019870:1-Phosphatidylinositol 4-Kinase