Selective autophagy impedes KSHV entry after recruiting the membrane damage sensor galectin-8 to virus-containing endosomes
Summary: Kaposi sarcoma-associated herpesvirus (KSHV) is an oncogenic γ-herpesvirus. Autophagy during KSHV entry has remained unexplored. We show that LC3 lipidation as a hallmark of autophagy is induced shortly after KSHV entry. LC3 co-localizes with KSHV in amphisomes during entry and loss of LC3...
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Elsevier
2024-12-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124724013706 |
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| author | Katarina Wendy Schmidt Charlotte Montespan Danielle Thompson Miriam S. Lucas Laure-Anne Ligeon Harald Wodrich Alexander S. Hahn Urs F. Greber Christian Münz |
| author_facet | Katarina Wendy Schmidt Charlotte Montespan Danielle Thompson Miriam S. Lucas Laure-Anne Ligeon Harald Wodrich Alexander S. Hahn Urs F. Greber Christian Münz |
| author_sort | Katarina Wendy Schmidt |
| collection | DOAJ |
| description | Summary: Kaposi sarcoma-associated herpesvirus (KSHV) is an oncogenic γ-herpesvirus. Autophagy during KSHV entry has remained unexplored. We show that LC3 lipidation as a hallmark of autophagy is induced shortly after KSHV entry. LC3 co-localizes with KSHV in amphisomes during entry and loss of LC3 lipidation increases infection. Accordingly, NDP52, a receptor of selective autophagy, was recruited to endocytosed viral particles, and its reduction increased KSHV infection. Additionally, virus particles co-localized with the endolysosome damage sensor galectin-8 upon KSHV entry and depletion of galectin-8 promoted KSHV infection. Compared with herpes simplex virus, listeriolysin, adenovirus, and influenza virus, and in contrast to what was previously thought about enveloped viruses, KSHV binding to EphA2 by its envelope protein gH causes endolysosomal membrane damage, akin to non-enveloped viruses and bacteria. Taken together, our study identifies an important anti-viral role for galectin-8, NDP52, and the autophagy machinery at virus-damaged endosomes, restricting KSHV entry by selective autophagy. |
| format | Article |
| id | doaj-art-5e3e4b63b6604084a7707d800fee0cfc |
| institution | DOAJ |
| issn | 2211-1247 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-5e3e4b63b6604084a7707d800fee0cfc2025-08-20T02:48:39ZengElsevierCell Reports2211-12472024-12-01431211501910.1016/j.celrep.2024.115019Selective autophagy impedes KSHV entry after recruiting the membrane damage sensor galectin-8 to virus-containing endosomesKatarina Wendy Schmidt0Charlotte Montespan1Danielle Thompson2Miriam S. Lucas3Laure-Anne Ligeon4Harald Wodrich5Alexander S. Hahn6Urs F. Greber7Christian Münz8Viral Immunobiology, Institute of Experimental Immunology, University of Zurich, 8057 Zurich, SwitzerlandViral Immunobiology, Institute of Experimental Immunology, University of Zurich, 8057 Zurich, SwitzerlandViral Immunobiology, Institute of Experimental Immunology, University of Zurich, 8057 Zurich, SwitzerlandScopeM – Scientific Center for Optical and Electron Microscopy, ETH Zurich, 8093 Zurich, SwitzerlandViral Immunobiology, Institute of Experimental Immunology, University of Zurich, 8057 Zurich, SwitzerlandCNRS UMR 5234, Fundamental Microbiology and Pathogenicity, University of Bordeaux, 33063 Bordeaux, FranceGerman Primate Center, University of Göttingen, 37077 Göttingen, GermanyInstitute of Molecular Life Sciences, University of Zurich, 8057 Zurich, SwitzerlandViral Immunobiology, Institute of Experimental Immunology, University of Zurich, 8057 Zurich, Switzerland; Corresponding authorSummary: Kaposi sarcoma-associated herpesvirus (KSHV) is an oncogenic γ-herpesvirus. Autophagy during KSHV entry has remained unexplored. We show that LC3 lipidation as a hallmark of autophagy is induced shortly after KSHV entry. LC3 co-localizes with KSHV in amphisomes during entry and loss of LC3 lipidation increases infection. Accordingly, NDP52, a receptor of selective autophagy, was recruited to endocytosed viral particles, and its reduction increased KSHV infection. Additionally, virus particles co-localized with the endolysosome damage sensor galectin-8 upon KSHV entry and depletion of galectin-8 promoted KSHV infection. Compared with herpes simplex virus, listeriolysin, adenovirus, and influenza virus, and in contrast to what was previously thought about enveloped viruses, KSHV binding to EphA2 by its envelope protein gH causes endolysosomal membrane damage, akin to non-enveloped viruses and bacteria. Taken together, our study identifies an important anti-viral role for galectin-8, NDP52, and the autophagy machinery at virus-damaged endosomes, restricting KSHV entry by selective autophagy.http://www.sciencedirect.com/science/article/pii/S2211124724013706CP: ImmunologyCP: Microbiology |
| spellingShingle | Katarina Wendy Schmidt Charlotte Montespan Danielle Thompson Miriam S. Lucas Laure-Anne Ligeon Harald Wodrich Alexander S. Hahn Urs F. Greber Christian Münz Selective autophagy impedes KSHV entry after recruiting the membrane damage sensor galectin-8 to virus-containing endosomes Cell Reports CP: Immunology CP: Microbiology |
| title | Selective autophagy impedes KSHV entry after recruiting the membrane damage sensor galectin-8 to virus-containing endosomes |
| title_full | Selective autophagy impedes KSHV entry after recruiting the membrane damage sensor galectin-8 to virus-containing endosomes |
| title_fullStr | Selective autophagy impedes KSHV entry after recruiting the membrane damage sensor galectin-8 to virus-containing endosomes |
| title_full_unstemmed | Selective autophagy impedes KSHV entry after recruiting the membrane damage sensor galectin-8 to virus-containing endosomes |
| title_short | Selective autophagy impedes KSHV entry after recruiting the membrane damage sensor galectin-8 to virus-containing endosomes |
| title_sort | selective autophagy impedes kshv entry after recruiting the membrane damage sensor galectin 8 to virus containing endosomes |
| topic | CP: Immunology CP: Microbiology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124724013706 |
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