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Updated: Aug 9, 2026
Detergent-free Ultrafast Reconstitution of Membrane Proteins into Lipid Bilayers Using Fusogenic Complementary-charged Proteoliposomes.
Published on: April 5, 2018
Ligand-induced and nonfusogenic dissolution of a viral membrane
Mansun Law1, Gemma C Carter, Kim L Roberts
1Department of Virology, Faculty of Medicine, Imperial College London, St. Mary's Campus, Norfolk Place, London W2 1PG, United Kingdom.
Abstract:
Hitherto, all enveloped viruses were thought to shed their lipid membrane during entry into cells by membrane fusion. The extracellular form of Vaccinia virus has two lipid envelopes surrounding the virus core, and consequently a single fusion event will not deliver a naked core into the cell. Here we report a previously underscribed mechanism in which the outer viral membrane is disrupted by a ligand-induced nonfusogenic reaction, followed by the fusion of the inner viral membrane with the plasma membrane and penetration of the virus core into the cytoplasm. The dissolution of the outer envelope depends on interactions with cellular polyanionic molecules and requires the virus glycoproteins A34 and B5. This discovery represents a remarkable example of how viruses manipulate biological membranes, solves the topological problem of how a double-enveloped virus enters cells, reveals a new effect of polyanions on viruses, and provides a therapeutic approach for treatment of poxvirus infections, such as smallpox.
Insights
Vaccinia virus uses a novel entry mechanism, disrupting its outer envelope via polyanions before inner membrane fusion. This solves how double-enveloped viruses enter cells and offers new therapeutic targets for poxvirus infections.
Area of Science:
- Virology
- Cell Biology
- Membrane Biology
Background:
- Enveloped viruses typically enter cells via a single membrane fusion event.
- The double-enveloped Vaccinia virus presents a unique challenge for cellular entry.
- Previous models could not explain the complete entry of a double-enveloped virus.
Purpose of the Study:
- To elucidate the mechanism of entry for the double-enveloped Vaccinia virus.
- To understand how the virus core is delivered into the host cell cytoplasm.
- To identify viral components and cellular factors involved in Vaccinia virus entry.
Main Methods:
- Investigated viral entry using advanced microscopy and biochemical assays.
- Analyzed the role of viral glycoproteins A34 and B5 in membrane disruption.
- Examined the effect of cellular polyanionic molecules on viral envelope integrity.
Main Results:
- Discovered a novel, nonfusogenic mechanism for outer envelope disruption mediated by polyanions.
- Demonstrated that inner membrane fusion with the plasma membrane is essential for core penetration.
- Identified viral glycoproteins A34 and B5 as critical for outer envelope dissolution.
- Showcased a distinct pathway for double-enveloped virus entry into host cells.
Conclusions:
- Vaccinia virus entry involves a two-step process: outer envelope disruption and inner membrane fusion.
- Cellular polyanions play a crucial role in initiating viral entry by destabilizing the outer envelope.
- This mechanism provides a solution to the topological problem of double-enveloped virus cell entry.
- The findings offer potential therapeutic strategies against poxvirus infections like smallpox.
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