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

• DOI: 10.15252/embj.2023113578
• Publication Date: 2023-04-21T07:20:55Z
• Authors: Sophie L Winter; Gonen Golani; Fabio Lolicato; Melina Vallbracht; Keerthihan Thiyag...; Samy Sid Ahmed; Christian Lüchten...; Oliver T Fackler; Britta Brügger; Thomas Hoenen; Walter Nickel; Ulrich S Schwarz; Petr Chlanda
• Keywords: VP40

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