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Updated: Aug 2, 2025

Modeling The Lifecycle Of Ebola Virus Under Biosafety Level 2 Conditions With Virus-like Particles Containing Tetracistronic Minigenomes
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The Ebola virus VP40 matrix layer undergoes endosomal disassembly essential for membrane fusion

Sophie L Winter1,2, Gonen Golani2,3, Fabio Lolicato4,5

  • 1Schaller Research Groups, Department of Infectious Diseases, Virology, University Hospital Heidelberg, Heidelberg, Germany.

The EMBO Journal
|April 21, 2023
PubMed

Insights

Ebola virus (EBOV) matrix protein VP40 disassembly, triggered by low endosomal pH, precedes viral membrane fusion. This pH-driven uncoating mechanism is crucial for efficient EBOV entry into host cells.

Area of Science:

  • Virology
  • Structural Biology
  • Cellular Biology

Background:

  • Ebola viruses (EBOVs) form filamentous virions critical for infection.
  • The viral matrix protein 40 (VP40) dictates virion shape and stability.
  • EBOV entry involves membrane fusion in late endosomes, but uncoating mechanisms remain unclear.

Purpose of the Study:

  • To investigate the structural changes of EBOV during host cell entry.
  • To elucidate the mechanism of virion uncoating and nucleocapsid release.
  • To understand the role of VP40 in EBOV entry and fusion.

Main Methods:

  • Structural analysis of EBOV during entry.
  • Investigation of VP40-lipid interactions under varying pH conditions.
  • Assays to determine the impact of VP40 matrix integrity on viral fusion.

Main Results:

  • The VP40 matrix disassembles before viral membrane fusion.
  • Low endosomal pH weakens VP40-lipid interactions, driving VP40 disassembly.
  • VP40 matrix disassembly lowers the energy barrier for fusion stalk formation, facilitating membrane fusion.

Conclusions:

  • pH-driven remodeling of the VP40 matrix acts as a molecular switch for EBOV entry.
  • VP40 uncoating is coupled to viral membrane fusion, enabling nucleocapsid release.
  • Understanding this mechanism provides insights into EBOV pathogenesis and potential therapeutic targets.
Keywords:
Ebola virusin situ cryo-ETmembrane fusionmembrane modeling and molecular dynamics simulationsvirus entry and uncoating

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