Measles Virus Fusion Machinery Activated by Sialic Acid Binding Globular Domain

Paramyxoviruses, including the human pathogenmeasles virus (MV) and the avian Newcastle disease virus (NDV), enter host cells through fusion of the viral envelope with the target cell membrane. This fusion is driven by the concerted action of two viral envelope glycoproteins: the receptor binding protein and the fusion protein (F). TheMV receptor binding protein (hemagglutinin [H]) attaches to proteinaceous receptors onhost cells, while the receptor binding protein ofNDV (hemagglutinin-neuraminidase [HN]) interactswith sialic acid-containing receptors. The receptor-boundHN/H triggers F to undergo conformational changes that render it competent tomediate fusion of the viral and cellularmembranes. Themechanismof fusion activation has been proposed to be different for sialic acid-binding viruses and proteinaceous receptor-binding viruses.We report that a chimeric protein containing theNDVHNreceptor binding region and theMVHstalk domain can activateMVF to fuse, suggesting that the signal to the stalk of a protein-binding receptor bindingmolecule can be transmitted froma sialic acid binding domain. By engineering theNDVHNglobu-lar domain to interactwith a proteinaceous receptor, the fusion activation signalwas preserved.Our findings are consistentwith a uni-fiedmechanismof fusion activation, at least for theParamyxovirinae subfamily, inwhich the receptor binding domains of the receptor binding proteins are interchangeable and the stalk determines the specificity of F activation. Paramyxoviruses enter their host cells by merging their enve-lope with that of the target cell in a fusion process driven by viral glycoproteins: a receptor binding protein and a fusion pro-tein (F) (1–5). Most paramyxoviruses (except members of th