Influenza Systems Virology – Molecular Signatures of Permissive Virus Infection

Viral epidemics and pandemics remain a constant threat for human population. This impact was particularly demonstrated by the recent transmission and explosive worldwide spread of a swine origin influenza virus among humans and the ongoing highly lethal infections with avian subtype strains. Influenza virus infections are a major cause for respiratory disease, which affect all age groups and can occur repeatedly in any particular individual. With ViroSign we suggest an interdisciplinary project that combines different aspects of systems biology including high-throughput experiments, imaging, and mathematical modeling. The use of high-throughput techniques incl. quantitative mass spectrometry-based proteomics and RNAi screens provides us with the unique opportunity to explore such complex systems. We aim to unravel the interaction network of each viral component as well as the proteome signature produced by the host-cell as a response to the pathogen. Experiments and theory will be directed towards the identification of cellular interactors and viral proteins responsible for a specific host cell response. Bioinformatics will build upon these results and integrate previous data on studies as the identification of host cell factors required for virus replication. This identification will allow the construction of a systemic model of influenza virus host interaction and is useful for making predictions of specific perturbations such as host and virus dependent mutations or the application of drugs and inhibitors to regulate certain processes.

Principal Investigators
Herrmann, Andreas Prof. Dr. rer. nat. (Details) (Molecular Biophysics)

Financer
BMBF

Duration of Project
Start date: 01/2013
End date: 05/2016

Publications
BMBF ViroSign
Mair, C., Sieben, C., Ludwig, K., Herrmann, A. (2014) Receptor Binding and pH stability - How Influenza A virus hemagglutinin affects host-specific virus infection. Biochim. Biophys. Acta 1838, 1153-1168

Wörmann, X., Lesch, M., Welke, R.-W., Okonechnikov, K., Abdurishid, M., Sieben, C., Geissner, A., Brinkmann, V., Kastner, M., Karner, A., Zhu, R., Hinterdorfer, P., Anish, C., Seeberger, P.H., Herrmann, A., Meyer, T.F., Karlas, A. (2016) Genetic characterization of an adapted pandemic 2009 H1N1 influenza virus that reveals improved replication rates in human lung epithelial cells. Virology, 492, 118-129.

Schelker, M., Mair, C.M., Jolmes, F., Welke, R.-W., Klipp, E., Herrmann, A., Flöttmann, M., Sieben, C. (2016) Viral RNA degradation and diffusion act as a bottleneck for the influenza A virus infection efficiency. Plos Comp. Biol. DOI:10.1371/journal.pcbi. 1005075 October 25, 2016

Schierhorn, K., Jolmes, F., Bespalowa, J., Saenger, S., Peteranderl, C., Dzieciolowski, J., Budt, M., Pleschka, S., Herrmann, A., Herold, S., Wolff, T. (2017) Influenza A virus virulence depends on two amino acids in the N-terminal domain of its NS1 protein facilitating inhibition of PKR. J. Virology 91, doi: 10.1128/JVI.00198-17

Sadewasser, A., Paki, K., Eichelbaum, K., Bogdanow, B., Saenger, S., Budt, M., Lesch, M., Hinz, K.-P., Herrmann, A., Karlas, A., Selbach, M., Wolff, Th. (2017) Quantitative proteomic approach identifies Vpr binding protein as novel host factor supporting permissive influenza A virus infections in human cells. Mol. Cell. Proteomics 16, 728-742.

Lesch, M., Luckner, M., Meyer, M., Gravenstein, I., Raftery, M., Sieben, C., Martin, L., Imai, A., Welke, R., Schönrich, G., Herrmann, A., Meyer, TF., Karlas, A. (2019) RNAi-based small molecule repositioning reveals clinically approved urea-based kinase inhibitors as broadly active antivirals. PLoS Pathogens, Mar 18;15(3):e1007601. doi:10.1371/journal.ppat.1007601. eCollection 2019 Mar.PMID: 30883607

Last updated on 2020-25-11 at 14:46