Association of the pr Peptides with Dengue Virus at Acidic pH Blocks Membrane Fusion
- 1 December 2009
- journal article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 83 (23), 12101-12107
- https://doi.org/10.1128/jvi.01637-09
Abstract
Flavivirus assembles into an inert particle that requires proteolytic activation by furin to enable transmission to other hosts. We previously showed that immature virus undergoes a conformational change at low pH that renders it accessible to furin (I. M. Yu, W. Zhang, H. A. Holdaway, L. Li, V. A. Kostyuchenko, P. R. Chipman, R. J. Kuhn, M. G. Rossmann, and J. Chen, Science 319:1834-1837, 2008). Here we show, using cryoelectron microscopy, that the structure of immature dengue virus at pH 6.0 is essentially the same before and after the cleavage of prM. The structure shows that after cleavage, the proteolytic product pr remains associated with the virion at acidic pH, and that furin cleavage by itself does not induce any major conformational changes. We also show by liposome cofloatation experiments that pr retention prevents membrane insertion, suggesting that pr is present on the virion in the trans -Golgi network to protect the progeny virus from fusion within the host cell.Keywords
This publication has 24 references indexed in Scilit:
- Structure of the Immature Dengue Virus at Low pH Primes Proteolytic MaturationScience, 2008
- Structure of Immature West Nile VirusJournal of Virology, 2007
- Structural analysis of viral nucleocapsids by subtraction of partial projectionsJournal of Structural Biology, 2007
- Crystal Structure of the West Nile Virus Envelope GlycoproteinJournal of Virology, 2006
- Crystal Structure of West Nile Virus Envelope Glycoprotein Reveals Viral Surface EpitopesJournal of Virology, 2006
- Structure of West Nile VirusScience, 2003
- Combining Electron Microscopic with X-Ray Crystallographic StructuresJournal of Structural Biology, 2001
- Three-Dimensional Reconstruction of Icosahedral Particles—The Uncommon LineJournal of Structural Biology, 1996
- A Model-Based Approach for Determining Orientations of Biological Macromolecules Imaged by Cryoelectron MicroscopyJournal of Structural Biology, 1996
- The envelope glycoprotein from tick-borne encephalitis virus at 2 Å resolutionNature, 1995