UMMS Affiliation

Department of Microbiology and Physiological Systems; Department of Biochemistry and Molecular Pharmacology

Publication Date

2020-07-02

Document Type

Article

Disciplines

Amino Acids, Peptides, and Proteins | Biochemistry, Biophysics, and Structural Biology | Biological Factors | Immunology and Infectious Disease | Lipids | Microbiology | Virus Diseases | Viruses

Abstract

Lassa virus (LASV) is the causative agent of Lassa hemorrhagic fever, a lethal disease endemic to Western Africa. LASV entry is mediated by the viral envelope glycoprotein (GP), a class I membrane fusogen and the sole viral surface antigen. Previous studies have identified components of the LASV entry pathway, including several cellular receptors and the requirement of endosomal acidification for infection. Here, we first demonstrate that incubation at a physiological temperature and pH consistent with the late endosome is sufficient to render pseudovirions, bearing LASV GP, non-infectious. Antibody binding indicates that this loss of infectivity is due to a conformational change in GP. Finally, we developed a single-particle fluorescence assay to directly visualize individual pseudovirions undergoing LASV GP-mediated lipid mixing with a supported planar bilayer. We report that exposure to endosomal pH at a physiologic temperature is sufficient to trigger GP-mediated lipid mixing. Furthermore, while a cellular receptor is not necessary to trigger lipid mixing, the presence of lysosomal-associated membrane protein 1 (LAMP1) increases the kinetics of lipid mixing at an endosomal pH. Furthermore, we find that LAMP1 permits robust lipid mixing under less acidic conditions than in its absence. These findings clarify our understanding of LASV GP-mediated fusion and the role of LAMP1 binding.

Keywords

Lassa virus, membrane fusion, single-particle fusion, virus entry

Rights and Permissions

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

DOI of Published Version

10.3390/v12070716

Source

Bulow U, Govindan R, Munro JB. Acidic pH Triggers Lipid Mixing Mediated by Lassa Virus GP. Viruses. 2020 Jul 2;12(7):E716. doi: 10.3390/v12070716. PMID: 32630688. Link to article on publisher's site

Journal/Book/Conference Title

Viruses

Related Resources

Link to Article in PubMed

PubMed ID

32630688

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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