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| Title | The Ebola virus VP40 matrix layer undergoes endosomal disassembly essential for membrane fusion. |
|---|---|
| Journal, issue, pages | EMBO J, Vol. 42, Issue 11, Page e113578, Year 2023 |
| Publish date | Jun 1, 2023 |
 Authors | Sophie L Winter / Gonen Golani / Fabio Lolicato / Melina Vallbracht / Keerthihan Thiyagarajah / Samy Sid Ahmed / Christian Lüchtenborg / Oliver T Fackler / Britta Brügger / Thomas Hoenen / Walter Nickel / Ulrich S Schwarz / Petr Chlanda /   |
| PubMed 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 ...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. |
 External links | EMBO J / PubMed:37082863 / PubMed Central |
| Methods | EM (tomography) |
| Structure data |  EMDB-15244: Tomogram of an Ebola VLP composed of GP, VP40, NP, VP24 and VP35 at pH 7.4 (Figure 1A-D)  EMDB-15268: Tomogram of an Ebola VLP composed of VP40 at pH 4.5 (Figure 1J)  EMDB-15951: Tomogram of an EBOV-infected Huh7 cell showing a late endosome with internalized EBOV particles  EMDB-15956: Tomogram of an extracellular EBOV particle adjacent to an EBOV-infected Huh7 cell |
