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β-Coronaviruses use lysosomal organelles for cellular egress

S Ghosh, TA Dellibovi-Ragheb, E Pak, Q Qiu, M Fisher, PM Takvorian, C Bleck, V Hsu, AR Fehr, S Perlman, SR Achar, View ORCID ProfileMR Straus, GR Whittaker, CAM de Haan, View ORCID ProfileG Altan-Bonnet, N Altan-Bonnet
doi: https://doi.org/10.1101/2020.07.25.192310
S Ghosh
1Laboratory of Host-Pathogen Dynamics, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda MD USA
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TA Dellibovi-Ragheb
1Laboratory of Host-Pathogen Dynamics, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda MD USA
2Federated Department of Biological Sciences, Rutgers-State University of New Jersey, Newark NJ USA
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E Pak
1Laboratory of Host-Pathogen Dynamics, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda MD USA
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Q Qiu
1Laboratory of Host-Pathogen Dynamics, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda MD USA
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M Fisher
1Laboratory of Host-Pathogen Dynamics, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda MD USA
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PM Takvorian
2Federated Department of Biological Sciences, Rutgers-State University of New Jersey, Newark NJ USA
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C Bleck
3Electron Microscopy Core Facility, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda MD USA
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V Hsu
4Division of Rheumatology, Inflammation and Immunity, Brigham and Women’s Hospital, Department of Medicine, Harvard Medical School, Boston MA USA
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AR Fehr
5Department of Microbiology and Immunology, University of Iowa, Iowa City, IA USA
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S Perlman
5Department of Microbiology and Immunology, University of Iowa, Iowa City, IA USA
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SR Achar
6Laboratory of Immunodynamics, National Cancer Institute, Bethesda MD USA
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MR Straus
7Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca NY USA
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  • ORCID record for MR Straus
GR Whittaker
7Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca NY USA
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CAM de Haan
8Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands
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G Altan-Bonnet
6Laboratory of Immunodynamics, National Cancer Institute, Bethesda MD USA
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  • ORCID record for G Altan-Bonnet
  • For correspondence: nihal.altan-bonnet@nih.gov gregoire.altan-bonnet@nih.gov
N Altan-Bonnet
1Laboratory of Host-Pathogen Dynamics, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda MD USA
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  • For correspondence: nihal.altan-bonnet@nih.gov gregoire.altan-bonnet@nih.gov
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Abstract

β-Coronaviruses are a family of positive-strand enveloped RNA viruses that include the severe acute respiratory syndrome-CoV2 (SARS-CoV2). While much is known regarding their cellular entry and replication pathways, their mode of egress remains uncertain; however, this is assumed to be via the biosynthetic secretory pathway by analogy to other enveloped viruses. Using imaging methodologies in combination with virus-specific reporters, we demonstrate that β-Coronaviruses utilize lysosomal trafficking for egress from cells. This pathway is regulated by the Arf-like small GTPase Arl8b; thus, virus egress is insensitive to inhibitors of the biosynthetic secretory pathway. Coronavirus infection results in lysosome deacidification, inactivation of lysosomal degradation and disruption of antigen presentation pathways. This coronavirus-induced exploitation of lysosomes provides insights into the cellular and immunological abnormalities observed in patients and suggests new therapeutic modalities.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted July 25, 2020.
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β-Coronaviruses use lysosomal organelles for cellular egress
S Ghosh, TA Dellibovi-Ragheb, E Pak, Q Qiu, M Fisher, PM Takvorian, C Bleck, V Hsu, AR Fehr, S Perlman, SR Achar, MR Straus, GR Whittaker, CAM de Haan, G Altan-Bonnet, N Altan-Bonnet
bioRxiv 2020.07.25.192310; doi: https://doi.org/10.1101/2020.07.25.192310
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β-Coronaviruses use lysosomal organelles for cellular egress
S Ghosh, TA Dellibovi-Ragheb, E Pak, Q Qiu, M Fisher, PM Takvorian, C Bleck, V Hsu, AR Fehr, S Perlman, SR Achar, MR Straus, GR Whittaker, CAM de Haan, G Altan-Bonnet, N Altan-Bonnet
bioRxiv 2020.07.25.192310; doi: https://doi.org/10.1101/2020.07.25.192310

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