Abstract
Intracellular cleavage of immature flaviviruses is a critical step in assembly that generates the membrane fusion potential of the E glycoprotein. With cryo-electron microscopy we show that the immature dengue particles undergo a reversible conformational change at low pH that renders them accessible to furin cleavage. At a pH of 6.0, the E proteins are arranged in a herringbone pattern with the pr peptides docked onto the fusion loops, a configuration similar to that of the mature virion. After cleavage, the dissociation of pr is pH-dependent, suggesting that in the acidic environment of the trans-Golgi network pr is retained on the virion to prevent membrane fusion. These results suggest a mechanism by which flaviviruses are processed and stabilized in the host cell secretory pathway.
Publication types
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
MeSH terms
- Cryoelectron Microscopy
- Crystallography, X-Ray
- Dengue Virus / chemistry*
- Dengue Virus / growth & development
- Dengue Virus / metabolism
- Dengue Virus / ultrastructure*
- Dimerization
- Endoplasmic Reticulum / virology
- Furin / metabolism
- Hydrogen-Ion Concentration
- Image Processing, Computer-Assisted
- Membrane Fusion
- Protein Conformation
- Viral Envelope Proteins / chemistry*
- Viral Envelope Proteins / metabolism
- Viral Fusion Proteins / chemistry
- Viral Fusion Proteins / metabolism
- Viral Matrix Proteins / chemistry*
- Viral Matrix Proteins / metabolism
- Virion / metabolism
- Virion / ultrastructure
- trans-Golgi Network / metabolism
- trans-Golgi Network / virology
Substances
- E-glycoprotein, Dengue virus type 2
- Viral Envelope Proteins
- Viral Fusion Proteins
- Viral Matrix Proteins
- Furin