1. Class II Virus Membrane Fusion Proteins: Mechanisms and Inhibition. MARGARET KIELIAN, Department of Cell Biology, Albert Einstein College Of Medicine, Bronx, NY 10461
Alphaviruses and flaviviruses infect cells through low pH-dependent membrane fusion reactions mediated by their structurally similar virus fusion proteins. During fusion these class II fusion proteins trimerize and refold to form hairpin-like structures with the domain III and stem regions folded back toward the target membrane-inserted fusion peptides. Using the alphavirus Semliki Forest virus (SFV) and the flavivirus dengue virus, we have demonstrated that exogenous domain III can function as a specific inhibitor of membrane fusion and infection. Surprisingly, the fusion protein stem region is not specifically required for SFV fusion activity. Our data reveal the existence of a relatively long-lived trimer core intermediate with which domain III stably interacts to initiate membrane fusion. We are using expressed protein domains to...
