DETERMINANTS OF VIRAL MEMBRANE FUSION

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The objective of this project is to investigate two novel findings concerning membrane fusion induced by retroviruses and paramyxoviruses. One specific aim will investigate the mechanism by which sequences in the cytoplasmic tail of viral glycoproteins can be a major determinant of membrane fusion activity. The C-terminal segment of the murine leukemia virus Env protein (the R peptide) is a potent inhibitor of virus-induced membrane fusion. Dr Compans will determine the precise amino acid sequences in the R peptide which are required for its fusion-inhibitory activity, and test the hypothesis that the inhibitory activity of the R peptide in a soluble or membrane-anchored form have an effect as a dominant negative inhibitor of fusion activity R peptide may cause a change in the conformation of the external domain of the envelope protein. Dr. Compans previously obtained evidence that a type-specific interaction occurs between the F and HN proteins which is essential for the fusion activity however, no information has been obtained about the precise nature of this interaction. Dr. Compans will determine whether F and HN are physically associated ont he surfaces of virions and/or infected cells, whether the F protein undergoes a conformational change which activates fusion activity, and whether this change requires its interaction with a homotypic HN protein. Investigate the mechanism by which peptide analogs of the F proteins act as highly specific inhibitors of the fusion activity of human parainfluenza viruses.