Felix REY
Structural Virology Unit
Institut Pasteur 25-28 rue du docteur Roux, 75015 Paris
 
Research area of the Unit
Our laboratory does comparative structural studies of viruses in order to understand molecular mechanisms involved in the various steps of the virus cycle. The scientific goals of our research are:
1- to provide a structural basis for understanding the molecular mechanisms of membrane fusion used by enveloped viruses to invade a cell;
2- to understand the principles of assembly of viral nucleocapsids;
3- to understand the molecular mechanism of genome replication by RNA viruses, both by structural and functional studies of RNA-dependent RNA polymerases and associated replication enzymes;
4- to combine the crystallographic data on isolated proteins with the structure of entire viruses obtained by cryomicroscopy in order to acquire insight about their function.

 
We study mostly viruses of global public health and/or of veterinary concern. The knowledge gained can be used for translational structure-based design of preventive or curative antiviral agents. Furthermore, these structural studies often reveal important evolutionary links between apparently unrelated viruses.
 
Contribution to the programme
 
One important goal is to understand the organization of a number of emerging viruses that are one of the topics of the IBEID Labex. These include arthropod borne viruses (“arboviruses”) such as chikungunya, dengue and yellow fever viruses, for which we have done structural studies in the past, and we are attempting now to identify the main antigenic determinants by crystallizing the complexes with neutralizing antibodies. E are also attempting to obtain structural information to high resolution from viruses of the Bunyaviridae family, which includes emerging human pathogens such as the Rift valley fever virus, the Schmallenberg virus of important veterinary concern, the Congo Crimea hemorrhagic fever virus and the hantaviruses. No structural information is available for any of the latter, and the crystal structures together with cryo-electron microscopy is likely to provide major advances to understand the organization and to find ways to combat these pathogens.
 
References over the past 5 years
1.      Mechanism of Dengue Virus Broad Cross-Neutralization by a Monoclonal Antibody.
Cockburn JJ, Navarro Sanchez ME,Fretes N, Urvoas A, Staropoli I,Kikuti CM,Coffey LL, Arenzana Seisdedos F, Bedouelle H,Rey FA. Structure. 2012 Feb 8;20(2):303-14.
2.      Structural insight into the neutralization mechanism of a higher primate antibody against dengue virus.Cockburn J, Navarro-Sanchez E, Goncalvez A, Zaitseva E, Stura EA,Kikuti CM, Duquerroy S, Chernomordik L, Lai CJ, Dussart P,Rey FA.Embo J. 2011 Dec 2;31(3):767-779.
3.      X-ray structure of the arenavirus glycoprotein GP2 in its postfusion conformation.
Igonet S, Vaney MC,Vonrhein C, Bricogne G, Stura EA, Hengartner H, Eschli B,Rey FA. Proc Natl Acad Sci U S A. 2011 Dec13;108(50):19967-19972.
4.      Glycoprotein organization of chikungunya virus particles revealed by X-ray crystallography.Voss JE, Vaney M-C, Duquerroy S, Vonrhein C, Girard-Blanc C, Crublet E, Thompson A, Bricogne G,Rey FA. Nature. 2010 Dec 2;468:709-712.
5.      Structure of a core fragment of glycoprotein H from Pseudorabies virus in complex with antibody.Backovic M, Dubois R, Cockburn JJ, Sharff AJ,Vaney MC, Granzow H, Klupp BG, Bricogne G, Mettenleiter TC,Rey FA. Proc Natl Acad Sci U S A. 2010 Dec 28;107(52):22635-40.
6.      The disulfide bonds in glycoprotein E2 of hepatitis C virus reveal the tertiary organization of the molecule.Krey T, d’Alayer J,Kikuti CM, Saulnier A,Damier-Piolle L, Petitpas I, Johansson DX,Tawar RG, Baron B, Robert B, England P, Persson MA, Martin A, Rey FA. PLoS Pathog. 2010 Feb 19;6(2):e1000762.
7.      Crystal structure of a nucleocapsid-like nucleoprotein-RNA complex of respiratory syncytial virus.Tawar RG, Duquerroy S, Vonrhein C, Varela PF, Damier-Piolle L, Castagné N, MacLellan K, Bedouelle H, Bricogne G, Bhella D, Eléouët JF,Rey FA. Science. 2009 Nov 27;326(5957):1279-83.