Journal article
β-Coronaviruses Use Lysosomes for Egress Instead of the Biosynthetic Secretory Pathway
Cell, Vol.183(6), pp.1520-1535.e14
12/10/2020
DOI: 10.1016/j.cell.2020.10.039
PMID: 33157038
Abstract
β-Coronaviruses are a family of positive-strand enveloped RNA viruses that includes the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Much is known regarding their cellular entry and replication pathways, but their mode of egress remains uncertain. Using imaging methodologies and virus-specific reporters, we demonstrate that β-coronaviruses utilize lysosomal trafficking for egress rather than the biosynthetic secretory pathway more commonly used by other enveloped viruses. This unconventional egress is regulated by the Arf-like small GTPase Arl8b and can be blocked by the Rab7 GTPase competitive inhibitor CID1067700. Such non-lytic release of β-coronaviruses results in lysosome deacidification, inactivation of lysosomal degradation enzymes, and disruption of antigen presentation pathways. β-Coronavirus-induced exploitation of lysosomal organelles for egress provides insights into the cellular and immunological abnormalities observed in patients and suggests new therapeutic modalities.
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•β-Coronaviruses do not use the biosynthetic secretory pathway to egress•β-Coronaviruses traffic to lysosomes and egress by Arl8b-dependent lysosomal exocytosis•Lysosomes are deacidified, and proteolytic enzymes are inactive in infected cells•Antigen processing and presentation are perturbed in β-coronavirus infection
Ghosh et al. provide evidence that β-coronaviruses do not use the biosynthetic secretory pathway typically used by enveloped viruses to leave infected cells. Instead, these viruses traffic to lysosomes for unconventional egress by Arl8b-dependent lysosomal exocytosis. Their non-lytic release results in lysosome deacidification, inactivation of lysosomal degradation enzymes, and disruption of antigen presentation.
Details
- Title: Subtitle
- β-Coronaviruses Use Lysosomes for Egress Instead of the Biosynthetic Secretory Pathway
- Creators
- Sourish Ghosh - Laboratory of Host-Pathogen Dynamics, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USATeegan A Dellibovi-Ragheb - Laboratory of Host-Pathogen Dynamics, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USAAdeline Kerviel - Laboratory of Host-Pathogen Dynamics, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USAEowyn Pak - Laboratory of Host-Pathogen Dynamics, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USAQi Qiu - Laboratory of Host-Pathogen Dynamics, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USAMatthew Fisher - Laboratory of Host-Pathogen Dynamics, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USAPeter M Takvorian - Federated Department of Biological Sciences, Rutgers-State University of New Jersey, Newark, NJ, USAChristopher Bleck - Electron Microscopy Core Facility, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USAVictor W Hsu - Division of Rheumatology, Inflammation and Immunity, Brigham and Women’s Hospital, Department of Medicine, Harvard Medical School, Boston, MA, USAAnthony R Fehr - Department of Microbiology and Immunology, University of Iowa, Iowa City, IA, USAStanley Perlman - Department of Microbiology and Immunology, University of Iowa, Iowa City, IA, USASooraj R Achar - lmmunodynamics Group - Laboratory of Integrative Cancer Immunology, National Cancer Institute, Bethesda, MD, USAMarco R Straus - Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY, USAGary R Whittaker - Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY, USACornelis A.M de Haan - Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the NetherlandsJohn Kehrl - B-Cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USAGrégoire Altan-Bonnet - lmmunodynamics Group - Laboratory of Integrative Cancer Immunology, National Cancer Institute, Bethesda, MD, USANihal Altan-Bonnet - Laboratory of Host-Pathogen Dynamics, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA
- Resource Type
- Journal article
- Publication Details
- Cell, Vol.183(6), pp.1520-1535.e14
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.cell.2020.10.039
- PMID
- 33157038
- ISSN
- 0092-8674
- eISSN
- 1097-4172
- Grant note
- DOI: 10.13039/100000002, name: National Institutes of Health, award: R01 NS36592, R37GM058615, F32-AI113973, R01 A1091985-05, R01AI35270; DOI: 10.13039/100000054, name: National Cancer Institute, award: R01 NS36592, R37GM058615, F32-AI113973, R01 A1091985-05, R01AI35270
- Language
- English
- Date published
- 12/10/2020
- Academic Unit
- Microbiology and Immunology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Infectious Disease (Pediatrics)
- Record Identifier
- 9984070158102771
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