uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Influenza Hemifusion Phenotype Depends on Membrane Context: Differences in Cell-Cell and Virus-Cell Fusion
Univ Virginia, Dept Mol Physiol & Biol Phys, Charlottesville, VA 22908 USA;Univ Virginia, Dept Biomed Engn, Charlottesville, VA 22908 USA.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular biophysics. Uppsala University, Science for Life Laboratory, SciLifeLab.
Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular biophysics. Univ Virginia, Dept Mol Physiol & Biol Phys, Charlottesville, VA 22908 USA;Univ Virginia, Dept Biomed Engn, Charlottesville, VA 22908 USA.
2018 (English)In: Journal of Molecular Biology, ISSN 0022-2836, E-ISSN 1089-8638, Vol. 430, no 5, p. 594-601Article in journal (Refereed) Published
Abstract [en]

Influenza viral entry into the host cell cytoplasm is accomplished by a process of membrane fusion mediated by the viral hemagglutinin protein. Hem agglutinin acts in a pH-triggered fashion, inserting a short fusion peptide into the host membrane followed by refolding of a coiled-coil structure to draw the viral envelope and host membranes together. Mutations to this fusion peptide provide an important window into viral fusion mechanisms and protein-membrane interactions. Here, we show that a well-described fusion peptide mutant, G1S, has a phenotype that depends strongly on the viral membrane context. The G1S mutant is well known to cause a "hemifusion" phenotype based on experiments in transfected cells, where cells expressing G1S hemagglutinin can undergo lipid mixing in a pH triggered fashion similar to virus but will not support fusion pores. We compare fusion by the G1S hemagglutinin mutant expressed either in cells or in influenza virions and show that this hemifusion phenotype occurs in transfected cells but that native virions are able to support full fusion, albeit at a slower rate and 10-100x reduced infectious titer. We explain this with a quantitative model where the G1S mutant, instead of causing an absolute block of fusion, alters the protein stoichiometry required for fusion. This change slightly slows fusion at high hemagglutinin density, as on the viral surface, but at lower hemagglutinin density produces a hemifusion phenotype. The quantitative model thus reproduces the observed virus-cell and cell-cell fusion phenotypes, yielding a unified explanation where membrane context can control the observed viral fusion phenotype. (C) 2018 Elsevier Ltd. All rights reserved.

Place, publisher, year, edition, pages
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD , 2018. Vol. 430, no 5, p. 594-601
Keywords [en]
influenza virus, membrane fusion, fusion peptide, stoichiometry, hemifusion
National Category
Microbiology in the medical area
Identifiers
URN: urn:nbn:se:uu:diva-352730DOI: 10.1016/j.jmb.2018.01.006ISI: 000429398200004PubMedID: 29355500OAI: oai:DiVA.org:uu-352730DiVA, id: diva2:1214776
Available from: 2018-06-07 Created: 2018-06-07 Last updated: 2018-06-07Bibliographically approved

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full textPubMed

Authority records BETA

Okamoto, KentaKasson, Peter M.

Search in DiVA

By author/editor
Okamoto, KentaKasson, Peter M.
By organisation
Molecular biophysicsScience for Life Laboratory, SciLifeLab
In the same journal
Journal of Molecular Biology
Microbiology in the medical area

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 16 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf