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Journal of Virology

Publication date: 2014-03
Volume: 88 Pages: 3048 - 51
ISSN: 0022-538X, 1070-6321 PMID: 24371067
Publisher: American Society for Microbiology (ASM)

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

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.