title: MEK inhibition impairs influenza B virus propagation without emergence of resistant variants.
abstract: Influenza A and B viruses are still a major worldwide threat. We demonstrate that influenza B virus infection induces signaling via the Raf/MEK/ERK cascade, a process required for efficient virus production. Expression of dominant-negative Raf and ERK mutants or treatment with a MEK inhibitor (U0126) strongly impaired viral propagation, while selective activation of the pathway resulted in increased virus titers. MEK inhibition appears to interfere with a distinct viral nuclear export process. Most importantly, no resistant virus variants emerged in the presence of U0126 demonstrating that influenza viruses cannot easily adapt to the missing cellular function.
authors.affiliation: Robert-Koch Institut, D-13353 Berlin, Germany. stephan.ludwig@uni-duesseldorf.de
authors.forename: Stephan
authors.initials: S
authors.lastname: Ludwig
authors.forename: Thorsten
authors.initials: T
authors.lastname: Wolff
authors.forename: Christina
authors.initials: C
authors.lastname: Ehrhardt
authors.forename: Walter Jürgen
authors.initials: WJ
authors.lastname: Wurzer
authors.forename: Jens
authors.initials: J
authors.lastname: Reinhardt
authors.forename: Oliver
authors.initials: O
authors.lastname: Planz
authors.forename: Stephan
authors.initials: S
authors.lastname: Pleschka
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D002460:Cell Line; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D014644:Genetic Variation; D009981:Influenza B virus / Q000235:genetics / Q000502:physiology*; D048369:MAP Kinase Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014779:Virus Replication
chemical_list: D004791:Enzyme Inhibitors; D019908:Proto-Oncogene Proteins c-raf; D020928:Mitogen-Activated Protein Kinases; D048369:MAP Kinase Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases