ebola virus glycoprotein needs an additional trigger, beyond proteolytic priming for membrane fusion埃博拉病毒糖蛋白需要额外的触发,除了膜融合蛋白水解启动.pdfVIP

Ebola Virus Glycoprotein Needs an Additional Trigger, beyond Proteolytic Priming for Membrane Fusion 1 2 2 2 1 1 Shridhar Bale , Tong Liu , Sheng Li , Yuhao Wang , Dafna Abelson , Marnie Fusco , 2 , Erica Ollmann Saphire1,3* Virgil L. Woods Jr. * 1 Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, United States of America, 2 Department of Medicine, University of California San Diego, La Jolla, California, United States of America, 3 The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California, United States of America Abstract Background: Ebolavirus belongs to the family filoviridae and causes severe hemorrhagic fever in humans with 50–90% lethality. Detailed understanding of how the viruses attach to and enter new host cells is critical to development of medical interventions. The virus displays a trimeric glycoprotein (GP1,2) on its surface that is solely responsible for membrane attachment, virus internalization and fusion. GP1,2 is expressed as a single peptide and is cleaved by furin in the host cells to yield two disulphide-linked fragments termed GP1 and GP2 that remain associated in a GP1,2 trimeric, viral surface spike. After entry into host endosomes, GP1,2 is enzymatically cleaved by endosomal cathepsins B and L, a necessary step in infection. However, the functional effects of the cleavage on the glycoprotein are unknown. Principal Findings: We demonstrate by antibody binding and Hydrogen-Deuterium Exchange Mass Spectrometry (DXMS) of glycoproteins from two different ebolaviruses that although enzymatic priming of GP1,2 is required for fusion, the priming itself does not initiate