MEK inhibition impairs influenza B virus propagation without emergence of resistant variants

FEBS Letters

Reinhardt, Jens¹  Pleschka, Stephan³  Ehrhardt, Christina⁴  Planz, Oliver²  Ludwig, Stephan⁴  Wurzer, Walter Jürgen⁴  Wolff, Thorsten¹ 

[1] Robert-Koch Institut, D-13353 Berlin, Germany;Institut für Immunologie, Bundesforschungsanstalt für Viruskrankheiten der Tiere (BFAV), D-72076 Tübingen, Germany;Institut für Virologie, Fachbereich Veterinärmedizin, Justus-Liebig-Universität, D-35392 Giessen, Germany;Institut of Molecular Medicine (IMM), Heinrich-Heine-Universität, D-40225 Düsseldorf, Germany

关键词: Influenza virus;    Mitogen-activated protein kinase cascade;    Mitogen-activated protein kinase/extracellular signal-regulated kinase inhibition;    Viral resistance;    MDCK;    Madin–Darby canine kidney;    RNP;    ribonucleoprotein complex;    MAPK;    mitogen-activated protein kinase;    ERK;    extracellular signal-regulated kinase;    MEK;    MAPK kinase/ERK kinase;    JNK;    c-Jun NH2-terminal kinase;    DMSO;    dimethylsulfoxide;   

DOI  :  10.1016/S0014-5793(04)00108-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown