The paramyxoviruses are important respiratory pathogens of both adults and children. The major cytopathic effect in paramyxovirus-infected cells is the formation of multi-nucleate syncytia. This is mediated by membrane fusion, induced by the two viral surface glycoproteins. One can identify many similarities between paramyxovirus fusion and those of other viruses, such as the influenza and human immunodeficiency viruses. However, unlike the other viruses, the paramyxovirus receptor recognition and fusion-promoting activities reside on two different surface glycoprotein spike structures, the attachment and fusion proteins, respectively. The long-term goal of our research has been to understand the early interactions of the paramyxovirus glycoproteins with the cell surface. The attachment and fusion proteins, once thought to be independent, have now been shown to take part in a specific interaction that is obligatorily linked to the conversion of the latter to its fusion-active form. The objective of this proposal is to understand the mechanism of formation of the complex between the two proteins and how this complex functions in the fusion process. Specific aspects of complex formation that will be elucidated include the role of receptor recognition by the terminal globular domain of the attachment protein, the changes this protein must undergo to take part in the interaction with the fusion protein and the sites on both proteins that mediate the interaction. This information will help elucidate how these important pathogens gain entry into, and spread between, cells, possibly identifying new anti-viral strategies for their control.
