7th Croucher-Pasteur Exchange Programme: Prof REY

Prof Félix REY (Structural Virology Unit, Institut Pasteur, Paris, France) has given a seminar on July 11, 2011 entitled: "Comparative structural studies of viral envelope glycoproteins".

Date: Monday, 11 July 2011 Time: 10:30 a.m. - 1:00 p.m. Venue: Mrs Chen Yang Foo Oi Telemedicine Centre, 2/F, William M W Mong Block, Faculty of Medicine Building, 21 Sassoon Road, Pokfulam, Hong Kong Abstract: I will outline the type of structural studies that we are currently pursuing in my laboratory, which aim at making comparative analyses, using different viruses, to explore the general ways in which enveloped viruses infect new cells, by delivering their genomic material into the cytoplasm. These studies provide insight into the mechanism of induction of the membrane fusion reaction, allow the characterization of the epitopes of recognized by neutralizing antibodies, and highlight potential receptor binding sites on the viral surface. I will show our overall results and describe the strategies that we are using to crystallize the envelope proteins from other viruses that should complement our current picture, and can be very informative to understand these processes in general. In particular, I will focus in a study of a complex of the dengue virus glycoprotein with a neutralizing antibody - termed 5H2 - isolated from a chimpanzee. The dengue virus envelope protein is made of three different domains - DI, DII and DIII. DIII is thought to be responsible for interactions with receptors, whereas DII carries the membrane fusion loop, and DI is located in between the two, at the center of an elongated rod-like molecule. Contrary to most murine antibodies that have been analyzed to date, which target DIII, the antibody repertoire of higher primates appears to contain only few antibodies that bind to DIII. The 5H2 antibody very potently neutralizes dengue virus serotype 4, binding with subnanomolar affinity to DI. This finding highlights the presence of an important epitope in this domain that should be considered for vaccine design in humans. Analysis of the binding mode shows that 5H2 inhibits the fusogenic transition from dimer to trimer – which is paramount to induce membrane fusion. This is in line with studies that show that the 5H2 antibody inhibits at a post-attachment step. Finally, the stoichiometry of binding, together with a Fab decoration pattern on the virion that is very similar to that of the E16 antibody that neutralizes the related West Nile virus, provide important information about the minimum number of free trimers that need to be present at the virion/target membrane contact area in order for infection to occur. Thus, in adition to describing the details of this important epitope, this study provides the first analysis demonstrating the need of several fusogenic trimers available simultaneously to induce membrane fusion by the flaviviruses.

Croucher-Pasteur Exchange Programme:

In collaboration with the International Affairs Department of Institut Pasteur and the Croucher Foundation, the Centre is establishing an exchange programme for students and post-doctoral fellows resident in Hong Kong in order to strengthen the scientific collaboration between Hong Kong and France. A 2 to 3 year scholarship covering travel, living and university registration expenses will be available for students and post-doctoral fellows resident in Hong Kong wishing to perform research work in laboratories of Institut Pasteur Paris. A lecture series of Pasteur scientists is organised to enable Hong Kong students to meet personally principal investigators from Institut Pasteur, know their scientific work and prospects of pursuing scientific work in their laboratories.