The Ebola virus VP40 matrix layer undergoes endosomal disassembly essential for membrane fusion

Abstract: Ebola viruses (EBOVs) assemble into filamentous virions, whose shape and stability are determined by the matrix viral protein 40 (VP40). Virus entry into host cells occurs via membrane fusion in late endosomes; however, the mechanism of how the remarkably long virions undergo uncoating, including virion disassembly and nucleocapsid release into the cytosol, remains unknown. Here, we investigate the structural architecture of EBOVs entering host cells and discover that the VP40 matrix disassembles prior to membrane fusion. We reveal that VP40 disassembly is caused by the weakening of VP40–lipid interactions driven by low endosomal pH that equilibrates passively across the viral envelope without a dedicated ion channel. We further show that viral membrane fusion depends on VP40 matrix integrity, and its disassembly reduces the energy barrier for fusion stalk formation. Thus, pH‐driven structural remodeling of the VP40 matrix acts as a molecular switch coupling viral matrix uncoating to membrane fusion during EBOV entry.

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch

References and Relationships

• Bibliographic citation: The Ebola virus VP40 matrix layer undergoes endosomal disassembly essential for membrane fusion ; day:21 ; month:04 ; year:2023 ; extent:20 ; The EMBO journal / European Molecular Biology Organization ; (21.04.2023) (gesamt 20)

Contributors, Places and Time

• Creator: Winter, Sophie L. ; Golani, Gonen ; Lolicato, Fabio ; Vallbracht, Melina ; Thiyagarajah, Keerthihan ; Ahmed, Samy Sid ; Lüchtenborg, Christian ; Fackler, Oliver Till ; Brügger, Britta ; Hoenen, Thomas ; Nickel, Walter ; Schwarz, Ulrich S. ; Chlanda, Petr

Further information

• DOI: 10.15252/embj.2023113578
• URN: urn:nbn:de:101:1-2023051715113238474040
• Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 14.08.2025, 10:49 AM CEST