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The phenuivirus Toscana virus makes an atypical use of vacuolar acidity to enter host cells

Toscana virus is a major cause of arboviral disease in humans in the Mediterranean basin during summer. However, early virus-host cell interactions and entry mechanisms remain poorly characterized. Investigating iPSC-derived human neurons and cell lines, we found that virus binding to the cell surfa...

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Main Authors: Koch, Jana (Author) , Xin, Qilin (Author) , Obr, Martin (Author) , Schäfer, Alicia (Author) , Rolfs, Nina (Author) , Anagho, Holda A. (Author) , Kudulyte, Aiste (Author) , Woltereck, Lea (Author) , Kummer, Susann (Author) , Campos, Joaquín (Author) , Uckeley, Zina Maria (Author) , Bell-Sakyi, Lesley (Author) , Kräusslich, Hans-Georg (Author) , Schur, Florian Km (Author) , Acuna, Claudio (Author) , Lozach, Pierre-Yves (Author)
Format: Article (Journal)
Language:English
Published: 14 Aug 2023
In: PLoS pathogens
Year: 2023, Volume: 19, Issue: 8, Pages: 1-32
ISSN:1553-7374
DOI:10.1371/journal.ppat.1011562
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1371/journal.ppat.1011562
Verlag, kostenfrei, Volltext: https://journals.plos.org/plospathogens/article?id= 10.1371/journal.ppat.1011562
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Author Notes:Jana Koch, Qilin Xin, Martin Obr, Alicia Schäfer, Nina Rolfs, Holda A. Anagho, Aiste Kudulyte, Lea Woltereck, Susann Kummer, Joaquin Campos, Zina M. Uckeley, Lesley Bell-Sakyi, Hans-Georg Kräusslich, Florian Km Schur, Claudio Acuna, Pierre-Yves Lozach
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Summary:Toscana virus is a major cause of arboviral disease in humans in the Mediterranean basin during summer. However, early virus-host cell interactions and entry mechanisms remain poorly characterized. Investigating iPSC-derived human neurons and cell lines, we found that virus binding to the cell surface was specific, and 50% of bound virions were endocytosed within 10 min. Virions entered Rab5a+ early endosomes and, subsequently, Rab7a+ and LAMP-1+ late endosomal compartments. Penetration required intact late endosomes and occurred within 30 min following internalization. Virus entry relied on vacuolar acidification, with an optimal pH for viral membrane fusion at pH 5.5. The pH threshold increased to 5.8 with longer pre-exposure of virions to the slightly acidic pH in early endosomes. Strikingly, the particles remained infectious after entering late endosomes with a pH below the fusion threshold. Overall, our study establishes Toscana virus as a late-penetrating virus and reveals an atypical use of vacuolar acidity by this virus to enter host cells.
Item Description:Gesehen am 11.06.2024
Physical Description:Online Resource
ISSN:1553-7374
DOI:10.1371/journal.ppat.1011562

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