Acidic residues in the membrane-proximal stalk region of vaccinia virus protein B5 are required for glycosaminoglycan-mediated disruption of the extracellular enveloped virus outer membrane
Open Access
- 1 July 2009
- journal article
- Published by Microbiology Society in Journal of General Virology
- Vol. 90 (7), 1582-1591
- https://doi.org/10.1099/vir.0.009092-0
Abstract
The extracellular enveloped virus (EEV) form of vaccinia virus (VACV) is surrounded by two lipid envelopes. This presents a topological problem for virus entry into cells, because a classical fusion event would only release a virion surrounded by a single envelope into the cell. Recently, we described a mechanism in which the EEV outer membrane is disrupted following interaction with glycosaminoglycans (GAGs) on the cell surface and thus allowing fusion of the inner membrane with the plasma membrane and penetration of a naked core into the cytosol. Here we show that both the B5 and A34 viral glycoproteins are required for this process. A34 is required to recruit B5 into the EEV membrane and B5 acts as a molecular switch to control EEV membrane rupture upon exposure to GAGs. Analysis of VACV strains expressing mutated B5 proteins demonstrated that the acidic stalk region between the transmembrane anchor sequence and the fourth short consensus repeat of B5 are critical for GAG-induced membrane rupture. Furthermore, the interaction between B5 and A34 can be disrupted by the addition of polyanions (GAGs) and polycations, but only the former induce membrane rupture. Based on these data we propose a revised model for EEV entry.Keywords
This publication has 36 references indexed in Scilit:
- The Vaccinia Virus B5 Protein Requires A34 for Efficient Intracellular Trafficking from the Endoplasmic Reticulum to the Site of Wrapping and Incorporation into Progeny VirionsJournal of Virology, 2008
- Vaccinia Virus A34 Glycoprotein Determines the Protein Composition of the Extracellular Virus EnvelopeJournal of Virology, 2008
- Two Distinct Low-pH Steps Promote Entry of Vaccinia VirusJournal of Virology, 2007
- Resistance of a vaccinia virus A34R deletion mutant to spontaneous rupture of the outer membrane of progeny virions on the surface of infected cellsVirology, 2007
- Vaccinia Virus Entry into Cells via a Low-pH-Dependent Endosomal PathwayJournal of Virology, 2006
- Ligand-induced and nonfusogenic dissolution of a viral membraneProceedings of the National Academy of Sciences, 2006
- Vaccinia virus intracellular enveloped virions move to the cell periphery on microtubules in the absence of the A36R proteinJournal of General Virology, 2005
- Functional Analysis of Vaccinia Virus B5R Protein: Role of the Cytoplasmic TailVirology, 1998
- THE UPTAKE AND DEVELOPMENT OF VACCINIA VIRUS IN STRAIN L CELLS FOLLOWED WITH LABELED VIRAL DEOXYRIBONUCLEIC ACIDThe Journal of cell biology, 1963
- THE DEVELOPMENT OF VACCINIA VIRUS IN EARLE'S L STRAIN CELLS AS EXAMINED BY ELECTRON MICROSCOPYThe Journal of cell biology, 1961