The late endosome-resident lipid bis(monoacylglycero)phosphate is a cofactor for Lassa virus fusion.

Arenavirus entry into host cells occurs through a low pH-dependent fusion with late endosomes that is mediated by the viral glycoprotein complex (GPC). The mechanisms of GPC-mediated membrane fusion and of virus targeting to late endosomes are not well understood. To gain insights into arenavirus fu...

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Autores principales:	Ruben M Markosyan, Mariana Marin, You Zhang, Fredric S Cohen, Gregory B Melikyan
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/5ecf10d3dd3942ff9db4e038d0ab1a62
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spelling	oai:doaj.org-article:5ecf10d3dd3942ff9db4e038d0ab1a622021-12-02T20:00:13ZThe late endosome-resident lipid bis(monoacylglycero)phosphate is a cofactor for Lassa virus fusion.1553-73661553-737410.1371/journal.ppat.1009488https://doaj.org/article/5ecf10d3dd3942ff9db4e038d0ab1a622021-09-01T00:00:00Zhttps://doi.org/10.1371/journal.ppat.1009488https://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Arenavirus entry into host cells occurs through a low pH-dependent fusion with late endosomes that is mediated by the viral glycoprotein complex (GPC). The mechanisms of GPC-mediated membrane fusion and of virus targeting to late endosomes are not well understood. To gain insights into arenavirus fusion, we examined cell-cell fusion induced by the Old World Lassa virus (LASV) GPC complex. LASV GPC-mediated cell fusion is more efficient and occurs at higher pH with target cells expressing human LAMP1 compared to cells lacking this cognate receptor. However, human LAMP1 is not absolutely required for cell-cell fusion or LASV entry. We found that GPC-induced fusion progresses through the same lipid intermediates as fusion mediated by other viral glycoproteins-a lipid curvature-sensitive intermediate upstream of hemifusion and a hemifusion intermediate downstream of acid-dependent steps that can be arrested in the cold. Importantly, GPC-mediated fusion and LASV pseudovirus entry are specifically augmented by an anionic lipid, bis(monoacylglycero)phosphate (BMP), which is highly enriched in late endosomes. This lipid also specifically promotes cell fusion mediated by Junin virus GPC, an unrelated New World arenavirus. We show that BMP promotes late steps of LASV fusion downstream of hemifusion-the formation and enlargement of fusion pores. The BMP-dependence of post-hemifusion stages of arenavirus fusion suggests that these viruses evolved to use this lipid as a cofactor to selectively fuse with late endosomes.Ruben M MarkosyanMariana MarinYou ZhangFredric S CohenGregory B MelikyanPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 17, Iss 9, p e1009488 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Ruben M Markosyan Mariana Marin You Zhang Fredric S Cohen Gregory B Melikyan The late endosome-resident lipid bis(monoacylglycero)phosphate is a cofactor for Lassa virus fusion.
description	Arenavirus entry into host cells occurs through a low pH-dependent fusion with late endosomes that is mediated by the viral glycoprotein complex (GPC). The mechanisms of GPC-mediated membrane fusion and of virus targeting to late endosomes are not well understood. To gain insights into arenavirus fusion, we examined cell-cell fusion induced by the Old World Lassa virus (LASV) GPC complex. LASV GPC-mediated cell fusion is more efficient and occurs at higher pH with target cells expressing human LAMP1 compared to cells lacking this cognate receptor. However, human LAMP1 is not absolutely required for cell-cell fusion or LASV entry. We found that GPC-induced fusion progresses through the same lipid intermediates as fusion mediated by other viral glycoproteins-a lipid curvature-sensitive intermediate upstream of hemifusion and a hemifusion intermediate downstream of acid-dependent steps that can be arrested in the cold. Importantly, GPC-mediated fusion and LASV pseudovirus entry are specifically augmented by an anionic lipid, bis(monoacylglycero)phosphate (BMP), which is highly enriched in late endosomes. This lipid also specifically promotes cell fusion mediated by Junin virus GPC, an unrelated New World arenavirus. We show that BMP promotes late steps of LASV fusion downstream of hemifusion-the formation and enlargement of fusion pores. The BMP-dependence of post-hemifusion stages of arenavirus fusion suggests that these viruses evolved to use this lipid as a cofactor to selectively fuse with late endosomes.
format	article
author	Ruben M Markosyan Mariana Marin You Zhang Fredric S Cohen Gregory B Melikyan
author_facet	Ruben M Markosyan Mariana Marin You Zhang Fredric S Cohen Gregory B Melikyan
author_sort	Ruben M Markosyan
title	The late endosome-resident lipid bis(monoacylglycero)phosphate is a cofactor for Lassa virus fusion.
title_short	The late endosome-resident lipid bis(monoacylglycero)phosphate is a cofactor for Lassa virus fusion.
title_full	The late endosome-resident lipid bis(monoacylglycero)phosphate is a cofactor for Lassa virus fusion.
title_fullStr	The late endosome-resident lipid bis(monoacylglycero)phosphate is a cofactor for Lassa virus fusion.
title_full_unstemmed	The late endosome-resident lipid bis(monoacylglycero)phosphate is a cofactor for Lassa virus fusion.
title_sort	late endosome-resident lipid bis(monoacylglycero)phosphate is a cofactor for lassa virus fusion.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/5ecf10d3dd3942ff9db4e038d0ab1a62
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The late endosome-resident lipid bis(monoacylglycero)phosphate is a cofactor for Lassa virus fusion.

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