The next social challenge to public health: the information environment.pptx
Understanding Rhabdovirus Fusion Machinery
1. Understanding the rhabdovirus fusion machinery Perspectives opened by dynamic structural virology Molecular and Structural Virology Laboratory CNRS – Gif sur Yvette Yves Gaudin CEA CHRU CNRS CPU INRA INRIA INSERM INSTITUT PASTEUR IRD
2. Rhabdovirus entry into the host cell Prototypes : rabies virus and VSV Enveloped viruses with a typical bullet shape Glycoprotein G mediates viral entry Endosome acidification Membrane fusion Virion endocytosis Receptor recognition
3. The membrane fusion pathway Complete fusion Stalk Hemifusion Fusion Pore Class I Paramyxovirus F Influenza HA HIV gp160 Class II Alphavirus E1 Flavivirus E Native or prefusion conformation Energy Final or postfusion conformation Fusion machineries
4. Rhabdovirus glycoprotein G: The prototype of the third class How does it work ? Internal fusion loops Transmembrane domain 446 466 495 CHO CHO pH-dependent equilibrium between these different states Prefusion state Activated state Postfusion state Receptor recognition Membrane interaction pH >7 pH < 6.5 pH 7.5 pH 5.5 One glycoprotein Several conformations
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6. Crystalline structures of VSV G TM Trimers Prefusion Postfusion Roche et al. Science 2006 ; Science 2007 Membrane Forme préfusion Protomers Prefusion Postfusion