Low pH and Anionic Lipid-dependent Fusion of Uukuniemi Phlebovirus to Liposomes.

The Journal of Biological Chemistry
David BittoJuha T Huiskonen

Abstract

Many phleboviruses (family Bunyaviridae) are emerging as medically important viruses. These viruses enter target cells by endocytosis and low pH-dependent membrane fusion in late endosomes. However, the necessary and sufficient factors for fusion have not been fully characterized. We have studied the minimal fusion requirements of a prototypic phlebovirus, Uukuniemi virus, in an in vitro virus-liposome assay. We show that efficient lipid mixing between viral and liposome membranes requires close to physiological temperatures and phospholipids with negatively charged headgroups, such as the late endosomal phospholipid bis(monoacylglycero)phosphate. We further demonstrate that bis(monoacylglycero)phosphate increases Uukuniemi virus fusion beyond the lipid mixing stage. By using electron cryotomography of viral particles in the presence or absence of liposomes, we observed that the conformation of phlebovirus glycoprotein capsomers changes from the native conformation toward a more elongated conformation at a fusion permissive pH. Our results suggest a rationale for phlebovirus entry in late endosomes.

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Citations

Mar 5, 2016·Traffic·Judith M White, Gary R Whittaker
May 24, 2016·Viruses·Amelina AlbornozNicole D Tischler
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Mar 7, 2021·Viruses·Jana KochPierre-Yves Lozach

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Methods Mentioned

BETA
fluorescence
electron cryotomography
dynamic light scattering
electron cryomicroscopy
confocal microscopy

Software Mentioned

Phyre
Jsubtomo
Zeiss ZEN Blue
IMOD

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The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.