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

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

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

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

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Pages (from-to)	3048-3051
Number of pages	4
Journal	Journal of Virology
Volume	88
Issue number	5
DOIs	https://doi.org/10.1128/JVI.03177-13
Publication status	Published - 2014

Keywords

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

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10.1128/JVI.03177-13

J. Virol.-2014-Thibaut-3048-51Final published version, 581 KB

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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.",

keywords = "1-Phosphatidylinositol 4-Kinase, Animals, Coxsackievirus Infections, Enterovirus, Genetic Fitness, Host-Pathogen Interactions, Mice, Mutation, Viral Proteins, Virulence, Virus Replication",

author = "Thibaut, \{Hendrik Jan\} and \{van der Schaar\}, \{Hilde M\} and Lanke, \{Kjerstin H W\} and Erik Verbeken and Martin Andrews and Pieter Leyssen and Johan Neyts and \{van Kuppeveld\}, \{Frank J M\}",

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doi = "10.1128/JVI.03177-13",

language = "English",

volume = "88",

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AU - Thibaut, Hendrik Jan

AU - van der Schaar, Hilde M

AU - Lanke, Kjerstin H W

AU - Verbeken, Erik

AU - Andrews, Martin

AU - Leyssen, Pieter

AU - Neyts, Johan

AU - van Kuppeveld, Frank J M

PY - 2014

Y1 - 2014

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AB - 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.

KW - 1-Phosphatidylinositol 4-Kinase

KW - Animals

KW - Coxsackievirus Infections

KW - Enterovirus

KW - Genetic Fitness

KW - Host-Pathogen Interactions

KW - Mice

KW - Mutation

KW - Viral Proteins

KW - Virulence

KW - Virus Replication

U2 - 10.1128/JVI.03177-13

DO - 10.1128/JVI.03177-13

M3 - Article

C2 - 24371067

SN - 0022-538X

VL - 88

SP - 3048

EP - 3051

JO - Journal of Virology

JF - Journal of Virology

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ER -

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

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Keywords

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