Ligand-induced and nonfusogenic dissolution of a viral membrane.
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.
Department of Virology, Faculty of Medicine, Imperial College London, St. Mary's Campus, Norfolk Place, London W2 1PG, United Kingdom.
Mansun
M
Law
Gemma C
GC
Carter
Kim L
KL
Roberts
Michael
M
Hollinshead
Geoffrey L
GL
Smith
D008024:Ligands; D008561:Membrane Fusion / Q000502:physiology*; D008854:Microscopy, Electron; D009233:Myxoma virus / Q000502:physiology / Q000648:ultrastructure; D014616:Vaccinia virus / Q000502:physiology* / Q000648:ultrastructure; D014759:Viral Envelope Proteins / Q000502:physiology; D014760:Viral Fusion Proteins / Q000502:physiology*; D010948:Viral Plaque Assay
D008024:Ligands; D014759:Viral Envelope Proteins; D014760:Viral Fusion Proteins