10779/crick.12608144.v1 Lesley J Calder Lesley J Calder Peter B Rosenthal Peter B Rosenthal Cryomicroscopy provides structural snapshots of influenza virus membrane fusion The Francis Crick Institute 2020 Animals Chick Embryo Cryoelectron Microscopy Endosomes Hydrogen-Ion Concentration Influenza A virus Liposomes Membrane Fusion Virus Attachment Virus Internalization Rosenthal FC001143 Developmental Biology Biophysics 11 Medical and Health Sciences 03 Chemical Sciences 06 Biological Sciences 2020-07-15 10:37:13 Journal contribution https://crick.figshare.com/articles/journal_contribution/Cryomicroscopy_provides_structural_snapshots_of_influenza_virus_membrane_fusion/12608144 The lipid-enveloped influenza virus enters host cells during infection by binding cell-surface receptors and, after receptor-mediated endocytosis, fusing with the membrane of the endosome and delivering the viral genome and transcription machinery into the host cell. These events are mediated by the hemagglutinin (HA) surface glycoprotein. At the low pH of the endosome, an irreversible conformational change in the HA, including the exposure of the hydrophobic fusion peptide, activates membrane fusion. Here we used electron cryomicroscopy and cryotomography to image the fusion of influenza virus with target membranes at low pH. We visualized structural intermediates of HA and their interactions with membranes during the course of membrane fusion as well as ultrastructural changes in the virus that accompany membrane fusion. Our observations are relevant to a wide range of protein-mediated membrane-fusion processes and demonstrate how dynamic membrane events may be studied by cryomicroscopy.