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The vaccinia chondroitin sulfate binding protein drives host membrane curvature to facilitate fusion

Accepted version
Peer-reviewed

Type

Article

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Abstract

Cellular attachment of viruses determines their cell tropism and species specificity. For entry, vaccinia, the prototypic poxvirus, relies on four binding proteins and an eleven-protein entry fusion complex. The contribution of the individual virus binding proteins to virion binding orientation and membrane fusion is unclear. Here, we show that virus binding proteins guide side-on virion binding and promote curvature of the host membrane towards the virus fusion machinery to facilitate fusion. Using a membrane-bleb model system together with super-resolution and electron microscopy we find that side-bound vaccinia virions induce membrane invagination in the presence of low pH. Repression or deletion of individual binding proteins reveals that three of four contribute to binding orientation, amongst which the chondroitin sulphate binding protein, D8, is required for host membrane bending. Consistent with low-pH dependent macropinocytic entry of vaccinia, loss of D8 prevents virion-associated macropinosome membrane bending, disrupts fusion pore formation and infection. Our results show that viral binding proteins are active participants in successful virus membrane fusion and illustrate the importance of virus protein architecture for successful infection.

Description

Keywords

Glycosaminoglycans, Membrane Bending, Membrane Fusion, Poxvirus, Virus Entry

Journal Title

EMBO Reports

Conference Name

Journal ISSN

1469-221X
1469-3178

Volume Title

Publisher

Wiley
Sponsorship
Wellcome Trust (101908/Z/13/Z)
Wellcome Trust (217191/Z/19/Z)

Version History

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2024-02-28 10:06:35
Published version added
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2023-12-19 00:31:55
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