Selective autophagy impedes KSHV entry after recruiting the membrane damage sensor galectin-8 to virus-containing endosomes.

Autor:	Schmidt KW; Viral Immunobiology, Institute of Experimental Immunology, University of Zurich, 8057 Zurich, Switzerland., Montespan C; Viral Immunobiology, Institute of Experimental Immunology, University of Zurich, 8057 Zurich, Switzerland., Thompson D; Viral Immunobiology, Institute of Experimental Immunology, University of Zurich, 8057 Zurich, Switzerland., Lucas MS; ScopeM - Scientific Center for Optical and Electron Microscopy, ETH Zurich, 8093 Zurich, Switzerland., Ligeon LA; Viral Immunobiology, Institute of Experimental Immunology, University of Zurich, 8057 Zurich, Switzerland., Wodrich H; CNRS UMR 5234, Fundamental Microbiology and Pathogenicity, University of Bordeaux, 33063 Bordeaux, France., Hahn AS; German Primate Center, University of Göttingen, 37077 Göttingen, Germany., Greber UF; Institute of Molecular Life Sciences, University of Zurich, 8057 Zurich, Switzerland., Münz C; Viral Immunobiology, Institute of Experimental Immunology, University of Zurich, 8057 Zurich, Switzerland. Electronic address: muenzc@immunology.uzh.ch.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2024 Nov 26; Vol. 43 (12), pp. 115019. Date of Electronic Publication: 2024 Nov 26.
DOI:	10.1016/j.celrep.2024.115019
Abstrakt:	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. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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