Charakterisierung der molekularen Mechanismen, die eine erfolgreiche Adaptation aviärer Influenza-A-Viren and den Menschen verhindern: der nukleare Import von vRNPs.
Zusammenfassung der Projektergebnisse
We could show that avian influenza A viruses have to escape MxA by acquiring not only Mx escape mutations but also mutations to compensate the associated loss of viral fitness. This loss of viral fitness seems to occur at the level of vRNP import, however, the reason(s) for this attenuation is not known. To identify cellular factors associated with vRNPs we performed mass spectrometry analysis in collaboration with the group of Andreas Pichlmaier at early time point post infections. This revealed multiple cellular factors associated with vRNPs, including factors involved in nuclear import. We hypothesize that the acquisition of Mx escape mutations interferes with binding of some of the vRNP associated factors, including the nuclear import factors.
Projektbezogene Publikationen (Auswahl)
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(2019) A protein-interaction network of interferon-stimulated genes extends the innate immune system landscape. Nature immunology 20 (4) 493–502
Hubel, Philipp; Urban, Christian; Bergant, Valter; Schneider, William M.; Knauer, Barbara; Stukalov, Alexey; Scaturro, Pietro; Mann, Angelika; Brunotte, Linda; Hoffmann, Heinrich H.; Schoggins, John W.; Schwemmle, Martin; Mann, Matthias; Rice, Charles M.;
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(2016) Influenza A viruses escape from MxA restriction at the expense of efficient nuclear vRNP import. Sci Rep. 6:23138
Götz V, Magar L, Dornfeld D, Giese S, Pohlmann A, Höper D, Kong BW, Jans DA, Beer M, Haller O, Schwemmle M
