Single-virus measurements of Zika membrane fusion and inactivation Robert J. Rawle1, Elizabeth Webster2, Steven G. Boxer2, Peter M. Kasson1,3 1Department of Molecular Physiology, University of Virginia; 2Department of Chemistry, Stanford University, 3Science for Life Laboratory, Department of Cell and Molecular Biology, Uppsala University
Zika virus, like many other emerging viruses, accomplishes cell entry via membrane fusion to endosomes. Mechanistic study of fusion typically lags the identification of emerging viral threats due to the need to develop a biochemically reconstituted system. We have developed a rapidly repurposable platform for measuring single-virus fusion that can be used both for mechanistic insight and to assess the activity of neutralizing antibodies and viral entry inhibitors. We demonstrate this platform on both influenza and Zika viruses. Mechanistically, we show that low pH and binding to a target membrane are sufficient for Zika membrane fusion. We also identify an off-pathway intermediate in Zika fusion related to viral inactivation. Measuring how this intermediate is affected by neutralizing antibodies in multiple viral strains may yield further insight for the selection of countermeasures effective against Zika that could avoid some of the challenges identified with some anti-flavivirus antibodies.
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