Authors: Conny Tolf Maria Gullberg JensOla Ekström Nina Jonsson A Michael Lindberg
Publish Date: 2009/06/16
Volume: 154, Issue: 8, Pages: 1271-1284
Abstract
Ljungan virus is a picornavirus isolated from Swedish and North American rodents Replication of Ljungan virus in cultured cells normally induces a weak and delayed cytopathic effect compared to that of many other picornaviruses However efficiently replicating Ljungan virus variants may evolve during serial passages in cell culture In this study we evaluate the significance of three substitutions in capsid protein VP0 and VP1 of a cellcultureadapted variant of the Swedish Ljungan virus 145SL strain In contrast to the parental strain this 145SLG variant grows to high titers in green monkey kidney cells and induces a distinct cytopathic effect Reverse genetic analyses demonstrated that each one of the individual capsid substitutions contributes to lytic replication in cell culture but also that expression of all three substitutions results in a 100 to 500fold increase in viral titers compared to viruses encoding single capsid substitutions In addition as indicated by detection of activated caspase3 and DNA fragmentation there seems to be an association between increased replication efficiency of lytic Ljungan virus variants and induction of an apoptotic response in infected green monkey kidney cellsWe are grateful to Kjell Edman Gun Frisk and JanÅke Liljeqvist for support and collaboration This work was supported by grants from the Swedish Knowledge Foundation Carl Trygger Foundation Apodemus AB and the PhD program in Medical Bioinformatics at Karolinska Institutet Stockholm Sweden
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