Bieri, Jan; Suter, Corinne; Caliaro, Oliver; Bartetzko, Seraina; Bircher, Cornelia; Ros, Carlos (2024). Globoside Is an Essential Intracellular Factor Required for Parvovirus B19 Endosomal Escape. Cells, 13(15) MDPI 10.3390/cells13151254
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Human parvovirus B19 (B19V), like most parvoviruses, possesses phospholipase A2 (PLA2) activity, which is thought to mediate endosomal escape by membrane disruption. Here, we challenge this model and find evidence for a mechanism of B19V entry mediated by the glycosphingolipid globoside without endosome disruption and retrograde transport to the Golgi. We show that B19V PLA2 activity requires specific calcium levels and pH conditions that are not optimal in endosomes. Accordingly, endosomal membrane integrity was maintained during B19V entry. Furthermore, endosomes remained intact when loaded with MS2 bacteriophage particles pseudotyped with multiple B19V PLA2 subunits, providing superior enzymatic potential compared to native B19V. In globoside knockout cells, incoming viruses are arrested in the endosomal compartment and the infection is blocked. Infection can be rescued by promoting endosomal leakage with polyethyleneimine (PEI), demonstrating the essential role of globoside in facilitating endosomal escape. Incoming virus colocalizes with Golgi markers and interfering with Golgi function blocks infection, suggesting that globoside-mediated entry involves the Golgi compartment, which provides conditions favorable for the lipolytic PLA2. Our study challenges the current model of B19V entry and identifies globoside as an essential intracellular receptor required for endosomal escape.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
08 Faculty of Science > Department of Chemistry, Biochemistry and Pharmaceutical Sciences (DCBP) |
Graduate School: |
Graduate School for Cellular and Biomedical Sciences (GCB) |
UniBE Contributor: |
Bieri, Jan Lukas, Suter, Corinne Dora, Caliaro, Oliver Stephan, Ros Bascunana, Carlos |
Subjects: |
500 Science > 570 Life sciences; biology 500 Science > 540 Chemistry |
ISSN: |
2073-4409 |
Publisher: |
MDPI |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
14 Aug 2024 11:26 |
Last Modified: |
14 Aug 2024 11:35 |
Publisher DOI: |
10.3390/cells13151254 |
PubMed ID: |
39120285 |
Uncontrolled Keywords: |
B19V endosomal escape globoside parvovirus B19 phospholipase A2 virus entry |
BORIS DOI: |
10.48350/199617 |
URI: |
https://boris.unibe.ch/id/eprint/199617 |
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