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

David Bitto, Steinar Halldorsson, Alessandro Caputo, Juha T Huiskonen

Research output: Contribution to journalArticle (Academic Journal)peer-review

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.

Original languageEnglish
Pages (from-to)6412-22
Number of pages11
JournalJournal of Biological Chemistry
Volume291
Issue number12
DOIs
Publication statusPublished - 18 Mar 2016

Keywords

  • Animals
  • Cell Line
  • Cricetinae
  • Glycoproteins/physiology
  • Hydrogen-Ion Concentration
  • Liposomes/chemistry
  • Lysophospholipids/chemistry
  • Monoglycerides/chemistry
  • Phlebovirus/chemistry
  • Viral Proteins/physiology
  • Virus Internalization

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