Structure and Working of Viral Fusion Machinery

This chapter discusses the structure and working of viral fusion machinery. The entry of enveloped viruses into cells requires the fusion of viral and cellular membranes, driven by conformational changes in viral glycoproteins. Structural studies have defined three classes of viral membrane fusion proteins. Despite their different structural organizations, all seem to have a common mechanism of action that generates the same lipid organizations during the fusion pathway. The entry of enveloped viruses into host cells requires binding of the virus to one or more receptors present at the cell surface, followed by fusion of the viral envelope with a cellular membrane. These steps are mediated by virally encoded glycoproteins that promote both receptor recognition and membrane fusion. The first crystal structure of a viral fusion protein ectodomain that has been determined is that of influenza virus hemagglutinin (HA) in its prefusion conformation. The structures of viral fusion glycoproteins, of which the conformational change is triggered at low pH, has allowed the identification of amino acid residues that play the role of pH-sensitive molecular switches.