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Morphogenesis and production of a Paramyxovirus particles

English title Morphogenesis and production of a Paramyxovirus particles
Applicant Roux Laurent
Number 138465
Funding scheme Project funding (Div. I-III)
Research institution Dépt Microbiologie et Médecine Moléculaire Faculté de Médecine Université de Genève
Institution of higher education University of Geneva - GE
Main discipline Experimental Microbiology
Start/End 01.10.2011 - 31.12.2013
Approved amount 260'992.00
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All Disciplines (2)

Discipline
Experimental Microbiology
Molecular Biology

Keywords (5)

Respiratory virus; Paramyxovirus; Virus particle morphogenesis; Virus protein structure function analysis; Vaccine vector

Lay Summary (English)

Lead
Lay summary
Using Sendai virus as the prototype for viruses of the Paramyxoviridae family, this project aims at providing a detailed molecular mechanism of virion assembly and production. This includes the unravelling of the basic role of each viral constituent, their interactions and the protein motifs involved. The project will make use of an original experimental approach allowing the study in the context of a regular infection, as opposed to the more frequently used approach involving expression from plasmids of the viral proteins, individually or in groups. Recombinant viruses are built with a siRNA target sequence (derived from the GFP gene, gfpt) incorporated in the 5’ untranslated region of the envelope viral protein gene or of a combination of genes. These viruses are then grown on cellular lines constitutively expressing the cognate siRNA and the effect of suppression of the product(s) of the targeted gene can then be studied. Recombinant viruses harbouring a second copy of the targeted gene, itself non targeted for suppression but carrying a HA-tag sequence allowing discrimination between the two proteins, are constructed. Mutations are then introduced in the supplementary gene to further develop a structure function analysis of the protein, in conditions of the wild type protein suppression. This “integrated suppression complementation system” (ISCS) has been set up and shown to work. This project will implement our knowledge about the molecular mechanisms of Paramyxovirus particle production. Hopefully, it will bring the example of SeV to an understanding that goes further than just a coherent way of thinking. On a less basic side, completion of this work should allow pseudotyping SeV with a whole range of glycoproteins. In combination with suppression of the endogenous glycoproteins, these pseudotyped SeV could serve as inactivated vaccine vectors for a whole range of respiratory viruses. Finally, the ability to express foreign glycoprotein(s) at the particle surface also opens the possibility to target the virus to a define range of cells presenting at their surface the cognate receptor. This approach can be used in two prospective applications: preparation of gene therapy and oncolytic vectors.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
. Minimal features of efficient incorporation of the hemagglutinin-neuraminidase protein into sendai virus particles.
Essaidi-Laziosi M Shevtsova A Gerlier D Roux L. (2014), . Minimal features of efficient incorporation of the hemagglutinin-neuraminidase protein into sendai virus particles., in J Virol, 88(1), 303-313.
Antagonism to human BST-2/tetherin by Sendai virus glycoproteins.
Bampi C Rasga L Roux L. (2013), Antagonism to human BST-2/tetherin by Sendai virus glycoproteins., in J Gen Vir, 94(6), 1211-1219.
Mutation of the TYTLE Motif in the Cytoplasmic Tail of the Sendai Virus Fusion Protein Deeply Affects Viral Assembly and Particle Production.
Essaidi-Laziosi M Shevtsova A Gerlier D Roux L (2013), Mutation of the TYTLE Motif in the Cytoplasmic Tail of the Sendai Virus Fusion Protein Deeply Affects Viral Assembly and Particle Production., in PlosOne, 8(12), e78074.
The cellular protein TIP47 restricts Respirovirus multiplication leading to decreased virus particle production.
Bampi C Grenet AS Caignard G Vidalain PO Roux L. (2013), The cellular protein TIP47 restricts Respirovirus multiplication leading to decreased virus particle production., in Virrus Research, 173, 354-363.
Sendai virus induced cytoplasmic actin remodeling correlates with efficient virus particle production.
Miazza V Mottet-Osman G Startchick S Chaponnier C Roux L. (2011), Sendai virus induced cytoplasmic actin remodeling correlates with efficient virus particle production., in Virology, 410(1), 7-16.

Collaboration

Group / person Country
Types of collaboration
Institut Pasteur, Paris France (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Centre international de recherche en microbiologie, Université Lyon 1, ENS de Lyon, Lyon France (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication

Associated projects

Number Title Start Funding scheme
122462 Le cycle de multiplication d’un Paramyxovirus: assemblage des différents constituants et production de particules virales 01.10.2008 Project funding (Div. I-III)

Abstract

The general objective of the project is to detail the molecular mechanisms of Sendai virus assembly. This includes the interactions required between the viral constituents as well as the protein motifs involved. The relevance of these motifs will have to be evaluated. The understanding of the mechanisms involved should eventually allow directed pseudotyping of SeV with selected glycoproteins. The experimental approach is base on an original "integrated suppression complementation system" (ISCS).
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