Entschlüsselung des vRNP-Interaktionsnetzwerkes, das für die Verpackung des viralen Genoms von Influenza-A-Viren benötigt wird.
Zusammenfassung der Projektergebnisse
Influenza A viruses (IAVs) are responsible for recurrent flu epidemics and occasional devastating pandemics. Their segmented genome consisting of 8 vRNAs favors evolution but requires a complex packaging mechanism that remains poorly understood. Our work and work by others suggest that the segmented genome of IAVs build a supramolecular complex held together by a redundant vRNA-vRNA interaction network and reveals a complex interplay between the vRNA packaging signals and the viral nucleoprotein (NP), suggesting that each viral ribonucleoprotein (vRNP), formed by the association of a vRNA with a polymerase complex and multiple copies of NP, has its own code. Our aim in the FluCode project was to decode the vRNP interaction network at the vRNA and NP levels. In the FluCode project, we successfully provided evidence that, surprisingly, disruption of SPLASH-identified vRNA-vRNA interactions does not affect the influenza A virus genome packaging, questioning the role of these interactions in genome packaging. We could further show that disruption of multiple influenza virus packaging signals results in various misassembled genome complexes. We could further show that specific acetylated lysine residues in the RNA-binding domain are part of the NP code required for the coordinated packaging process of the eight different viral genomes. Finally, we obtained evidence showing that within viral particles the packaging signals constraint the vRNA structure.
Projektbezogene Publikationen (Auswahl)
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The influenza A virus genome packaging network — complex, flexible and yet unsolved. Nucleic Acids Research, 50(16), 9023-9038.
Jakob, Celia; Paul-Stansilaus, Rithu; Schwemmle, Martin; Marquet, Roland & Bolte, Hardin
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Disruption of influenza virus packaging signals results in various misassembled genome complexes. Journal of Virology, 97(10).
Girard, Justine; Jakob, Celia; Toews, Lina Kathrin; Fuchs, Jonas; Pohlmann, Anne; Franzke, Kati; Kolesnikova, Larissa; Jeney, Csaba; Beer, Martin; Bron, Patrick; Schwemmle, Martin & Bolte, Hardin
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Sequential disruption of SPLASH-identified vRNA–vRNA interactions challenges their role in influenza A virus genome packaging. Nucleic Acids Research, 51(12), 6479-6494.
Jakob, Celia; Lovate, Gabriel L.; Desirò, Daniel; Gießler, Lara; Smyth, Redmond P.; Marquet, Roland; Lamkiewicz, Kevin; Marz, Manja; Schwemmle, Martin & Bolte, Hardin
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Functionality of IAV packaging signals depends on site-specific charges within the viral nucleoprotein. Journal of Virology, 98(4).
Ciminski, Kevin; Flore, Viktoria; Jakob, Celia; Mues, Helen; Smedegaard, Frederiksen Anne; Schwemmle, Martin; Bolte, Hardin & Giese, Sebastian
