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MEK inhibition impairs influenza B virus propagation without emergence of resistant variants
Author(s) -
Ludwig Stephan,
Wolff Thorsten,
Ehrhardt Christina,
Wurzer Walter Jürgen,
Reinhardt Jens,
Planz Oliver,
Pleschka Stephan
Publication year - 2004
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(04)00108-5
Subject(s) - virus , virology , mapk/erk pathway , influenza a virus , biology , mutant , viral entry , titer , function (biology) , microbiology and biotechnology , viral replication , signal transduction , gene , genetics
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.