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The role of the influenza virus matrix protein M1 in budding adn virus release

Objective

Enveloped viruses, such as influenza, acquire their outer lipid envelope by budding from the membrane of the infected host before being released in the extra-cellular space by membrane fission. In these last steps of the virus infection cycle, matrix proteins connecting capsid with the lipid envelope often play a key role in assembly and budding of newly produced virions. In spite of the widely acknowledged impact on public health and economy of influenza epidemics, the processes facilitating egression of the flu virus are only poorly understood. The goal of this project is to investigate the mechanisms by which Influenza escapes from its host. We will, in particular, focus on the role of its matrix protein M1. Our approach is based on the use of a combination of minimal cell membrane models produced in vitro upon self-assembly of lipids. Using supported lipid bilayers (SLB), giant unilamellar vesicles
(GUV), as well as membrane nanotubes of compositions reflecting those of the host´s plasma membrane, we will provide a physical understanding to the role of M1 in facilitating virus assembly into a bud and release from the host. Through our study, we will elucidate whether M1 can promote budding and fission via scaffolding and whether the formation of lipid microdomains can help overcoming the energy barrier required for membrane abscission. Once the system is established, it will be extended to mimic the role the riboneucleoproteins core (RNPs), using nanoparticles of geometries similar to the viral capsid. Furthermore, the contribution of other viral components will be taken into consideration. In particular, we will look for a synergy between M1 and the ion channel M2 as the latter is believed to be involved in fission. A detailed understanding of the individual steps of the viruse’s life cycle is not only interesting from a fundamental point of view but is likely to greatly benefit to the development of more efficient antiviral drugs and treatments.

Call for proposal

FP7-PEOPLE-2012-IEF
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Coordinator

INSTITUT CURIE
Address
Rue D'ulm 26
75231 Paris
France
Activity type
Research Organisations
EU contribution
€ 202 405,80
Administrative Contact
Corinne Cumin (Mrs.)