Judith Lang, Patrick Bohn, Hilal Bhat, Holger Jastrow, Bernd Walkenfort, Feyza Cansiz, Julian Fink, Michael Bauer, Fabian Schumacher, Burkhard Kleuser, Karl S. Lang
- Macrophages have important protective functions during infection with herpes simplex virus type 1 (HSV-1). However, molecular mechanisms that restrict viral propagation and protect from severe disease are unclear. Here we show that macrophages take up HSV-1 via endocytosis and transport the virions into multivesicular bodies (MVBs). In MVBs, acid ceramidase (aCDase) converts ceramide into sphingosine and increases the formation of sphingosine-rich intraluminal vesicles (ILVs). Once HSV-1 particles reach MVBs, sphingosine-rich ILVs bind to HSV-1 particles, which restricts fusion with the limiting endosomal membrane and prevents cellular infection. Lack of aCDase in macrophage cultures or in Asah1(-/-) mice results in replication of HSV-1 and Asah1(-/-) mice die soon after systemic or intravaginal inoculation. The treatment of macrophages with sphingosine enhancing compounds blocks HSV-1 propagation, suggesting a therapeutic potential of this pathway. In conclusion, aCDase loads ILVs with sphingosine, which prevents HSV-1 capsids fromMacrophages have important protective functions during infection with herpes simplex virus type 1 (HSV-1). However, molecular mechanisms that restrict viral propagation and protect from severe disease are unclear. Here we show that macrophages take up HSV-1 via endocytosis and transport the virions into multivesicular bodies (MVBs). In MVBs, acid ceramidase (aCDase) converts ceramide into sphingosine and increases the formation of sphingosine-rich intraluminal vesicles (ILVs). Once HSV-1 particles reach MVBs, sphingosine-rich ILVs bind to HSV-1 particles, which restricts fusion with the limiting endosomal membrane and prevents cellular infection. Lack of aCDase in macrophage cultures or in Asah1(-/-) mice results in replication of HSV-1 and Asah1(-/-) mice die soon after systemic or intravaginal inoculation. The treatment of macrophages with sphingosine enhancing compounds blocks HSV-1 propagation, suggesting a therapeutic potential of this pathway. In conclusion, aCDase loads ILVs with sphingosine, which prevents HSV-1 capsids from penetrating into the cytosol.…
MetadatenVerfasserangaben: | Judith LangORCiDGND, Patrick BohnORCiDGND, Hilal BhatORCiDGND, Holger JastrowORCiDGND, Bernd WalkenfortORCiDGND, Feyza CansizGND, Julian Fink, Michael BauerORCiD, Fabian SchumacherORCiDGND, Burkhard KleuserORCiDGND, Karl S. LangORCiD |
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URN: | urn:nbn:de:kobv:517-opus4-515661 |
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DOI: | https://doi.org/10.25932/publishup-51566 |
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ISSN: | 1866-8372 |
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Titel des übergeordneten Werks (Deutsch): | Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe |
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Schriftenreihe (Bandnummer): | Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe (1400) |
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Publikationstyp: | Postprint |
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Sprache: | Englisch |
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Datum der Erstveröffentlichung: | 12.03.2020 |
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Erscheinungsjahr: | 2020 |
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Veröffentlichende Institution: | Universität Potsdam |
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Datum der Freischaltung: | 14.03.2024 |
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Freies Schlagwort / Tag: | immunology; infection; membrane fusion; phagocytosis; sphingolipids |
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Ausgabe: | 1 |
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Aufsatznummer: | 1338 |
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Seitenanzahl: | 17 |
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Quelle: | Nat Commun 11, 1338 (2020). https://doi.org/10.1038/s41467-020-15072-8 |
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Organisationseinheiten: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Ernährungswissenschaft |
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DDC-Klassifikation: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
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Peer Review: | Referiert |
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Publikationsweg: | Open Access / Green Open-Access |
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Lizenz (Deutsch): | CC-BY - Namensnennung 4.0 International |
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Externe Anmerkung: | Bibliographieeintrag der Originalveröffentlichung/Quelle |
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