SPP 1175:  Dynamics of Cellular Membranes and their Exploitation by Viruses

• Subject Area: Medicine ; Biology
• Term: from 2005 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5472160

The primary aim of this Priority Programme is to study the similarities and differences in the envelopment of viruses and cellular structures at various cell membranes. Enveloped viruses are released from cells or subcellular compartments in a budding process which makes use of cellular machineries. Thus, it appears likely, that the parallel and interdisciplinary analysis of diverse envelopment processes will lead to the discovery of general principles and molecular mechanisms and will thus have a significant added value. Little is currently known about these processes, but recent results - partly obtained by research groups from Germany - provided first insights into the underlying mechanisms. Examples are the insertion of nuclear pore complexes into the intact nuclear envelope and the egress of herpesvirus capsids from the nucleus, the appropriation of macromolecular complexes used in formation of multivesicular bodies for the budding of viruses, and the formation and maintenance of lipid microdomains which can serve as platforms for virus release. Applying the study of viruses to cell biology questions and vice versa has already in the past led to major advances in our understanding of cellular processes, and this programme will rebuild this bridge for the study of a fundamental question.
The research programme addresses many of the most important human and animal pathogens including HIV, hemorrhagic fever viruses (e.g. ebola and lassa virus), herpesviruses, hepatitis C virus and poxviruses. Moreover, results obtained are likely to also apply to other (e.g. SARS coronavirus) or yet unknown pathogens. A detailed understanding of the underlying mechanisms at a molecular and structural level will also identify new targets for therapeutic intervention. A further important aspect is to apply novel and highly sophisticated technologies to the study of membrane envelopment. The Priority Programme requires the combination of methods and the interdisciplinary interaction that is only possible in a programme on a national scale. The topic of this research programme is very timely and is considered an important research priority also on an international scale. Several of the initial observations defining the research concept have been made by research groups participating in this Priority Programme.

• DFG Programme: Priority Programmes
• International Connection: France

Projects

• Analysis of the human immnunodeficiency virus budding site (Applicant Kräusslich, Hans-Georg )
• Application of fluorescence microscopy and live-cell imaging to elucidate the dynamics of viral assembly and budding (Applicant Lamb, Don C. )
• Budding of Marburg virus (Applicant Becker, Stephan )
• Cellular proteins and pathways involved in subviral particle release of foamy viruses (Applicant Lindemann, Dirk )
• Central tasks of the research priority program (Applicant Kräusslich, Hans-Georg )
• Dissecting the biogenesis of Vaccinia Virus membranes using cryo-electron tomography (Applicant Krijnse Locker, Ph.D., Jacomine )
• Dissection of canonical and alternative pathways for human cytomegalovirus secondary envelopment using morphogenetic mutants and novel correlative microscopic methods (Applicants Mertens, Thomas ;  Walther, Paul )
• Elucidating the mechanism of nuclear pore complex assembly in intact nuclei of live cells (Applicant Ellenberg, Jan )
• Insertion of nuclear pore complexes into the nuclear membrane (Applicant Dabauvalle, Marie-Christine )
• Investigating the relevance of lipid microdomains for (HI) virus protein assembly and virus budding in an artifical cell environment (Applicant Schwille, Petra )
• Lassa virus assembly and release mediated by interplay of viral proteins and cellular factors (Applicant Garten, Wolfgang )
• Lateral sorting of proteins into lipid-rafts and protein-protein interactions as prerequisite for assembly of influenza virus: A complementary biophysical approach on model membranes and living cells (Applicants Herrmann, Andreas ;  Veit, Michael )
• Lipidology of host cells and viral envelopes (Applicant Brügger, Britta )
• Macrophage killing mechanisms for intra-phagosomal mycobacteria (Applicant Griffiths, Ph.D., Gareth )
• Measles virus M protein trafficking: identification of pathways, functional domains, modifications and cell specificity (Applicant Schneider-Schaulies, Sibylle )
• Membrane budding by rabies virus matrix- and phosphoprotein (Applicants Conzelmann, Karl-Klaus ;  Finke, Stefan )
• Molecular mechanisms of primary and secondary envelopment in herpesvirus morphogenesis (Applicant Mettenleiter, Thomas C. )
• Raft based sorting and domain-induced budding of post-Golgi transport carriers (Applicant Simons, Kai )
• Role of ubiquitin in retrovirus budding (Applicant Schubert, Ulrich )
• Structural analysis of herpesvirus assembly by cryo electron tomography (Applicant Grünewald, Kay )
• Structural characterization of EXCRT-III assemblies (Applicant Weissenhorn, Winfried )
• Structure and arrangement of viral proteins in HIV, Marburg and Influenza viruses (Applicant Briggs, John )
• The function of microtubules for the secondary envelopment of Herpes Simplex Virus in neurons (Applicant Sodeik, Beate )
• Viral genes governing CMV capsid export (Applicant Koszinowski, Ulrich H. )

• Spokesperson: Professor Dr. Hans-Georg Kräusslich