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β-Coronaviruses Use Lysosomal Organelles for Cellular Egress

40 Pages Posted: 20 Jul 2020 Sneak Peek Status: Under Review

See all articles by Sourish Ghosh

Sourish Ghosh

National Institutes of Health - Laboratory of Host-Pathogen Dynamics

Teegan Dellibovi-Ragheb

National Institutes of Health - Laboratory of Host-Pathogen Dynamics

Eowyn Pak

National Institutes of Health - Laboratory of Host-Pathogen Dynamics

Qi Qiu

National Institutes of Health - Laboratory of Host-Pathogen Dynamics

Matthew Fisher

National Institutes of Health - Laboratory of Host-Pathogen Dynamics

Peter Takvorian

Rutgers State University of New Jersey, Newark - Department of Biological Sciences

Christopher Bleck

National Institutes of Health (NIH) - Electron Microscopy Core Facility

Victor Hsu

Harvard Medical School - Division of Rheumatology

Anthony Fehr

University of Iowa - Department of Microbiology and Immunology

Stanley Perlman

University of Iowa - Department of Microbiology and Immunology

Sooraj Achar

National Cancer Institute - Laboratory of Immunodynamics

Marco Straus

Cornell University - Department of Microbiology and Immunology

Gary Whittaker

Cornell University - Department of Microbiology and Immunology

Xander de Haan

Utrecht University - Department of Biomolecular Health Sciences

Gregoire Altan-Bonnet

Memorial Sloan Kettering Cancer Center - ImmunoDynamics Group; Memorial Sloan Kettering Cancer Center - Center for Cancer Systems Biology

Nihal Altan-Bonnet

National Institutes of Health (NIH) - National Heart, Lung, and Blood Institute

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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.

Funding: NAB, SG, TDR, EP, QQ, MF and CB were supported with NHLBI/NIH; GAB and SRA were supported with NCI/NIH intramural funds. PMT was supported by NIH R01 A1091985-05; SP by NIH R01 NS36592 and AF by F32-AI113973; VH by NIH R37GM058615; GW by NIH R01AI35270.

Conflict of Interest: None.

Suggested Citation

Ghosh, Sourish and Dellibovi-Ragheb, Teegan and Pak, Eowyn and Qiu, Qi and Fisher, Matthew and Takvorian, Peter and Bleck, Christopher and Hsu, Victor and Fehr, Anthony and Perlman, Stanley and Achar, Sooraj and Straus, Marco and Whittaker, Gary and de Haan, Xander and Altan-Bonnet, Gregoire and Altan-Bonnet, Nihal, β-Coronaviruses Use Lysosomal Organelles for Cellular Egress. Available at SSRN: https://ssrn.com/abstract=3654626 or http://dx.doi.org/10.2139/ssrn.3654626
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Sourish Ghosh

National Institutes of Health - Laboratory of Host-Pathogen Dynamics ( email )

United States

Teegan Dellibovi-Ragheb

National Institutes of Health - Laboratory of Host-Pathogen Dynamics ( email )

United States

Eowyn Pak

National Institutes of Health - Laboratory of Host-Pathogen Dynamics ( email )

United States

Qi Qiu

National Institutes of Health - Laboratory of Host-Pathogen Dynamics ( email )

United States

Matthew Fisher

National Institutes of Health - Laboratory of Host-Pathogen Dynamics ( email )

United States

Peter Takvorian

Rutgers State University of New Jersey, Newark - Department of Biological Sciences ( email )

180 University Avenue
Newark, NJ 07102
United States

Christopher Bleck

National Institutes of Health (NIH) - Electron Microscopy Core Facility ( email )

9000 Rockville Pike
Bethesda, MD 20892
United States

Victor Hsu

Harvard Medical School - Division of Rheumatology ( email )

1875 Cambridge Street
Cambridge, MA 02138
United States

Anthony Fehr

University of Iowa - Department of Microbiology and Immunology ( email )

United States

Stanley Perlman

University of Iowa - Department of Microbiology and Immunology ( email )

United States

Sooraj Achar

National Cancer Institute - Laboratory of Immunodynamics ( email )

9609 Medical Center Drive
Bethesda, MD 20892
United States

Marco Straus

Cornell University - Department of Microbiology and Immunology ( email )

United States

Gary Whittaker

Cornell University - Department of Microbiology and Immunology ( email )

United States

Xander De Haan

Utrecht University - Department of Biomolecular Health Sciences ( email )

Netherlands

Gregoire Altan-Bonnet

Memorial Sloan Kettering Cancer Center - ImmunoDynamics Group ( email )

New York, NY 10065
United States

Memorial Sloan Kettering Cancer Center - Center for Cancer Systems Biology ( email )

New York, NY 10065
United States

Nihal Altan-Bonnet (Contact Author)

National Institutes of Health (NIH) - National Heart, Lung, and Blood Institute

73 Mr. Wayte Avenue
Bethesda, MD 01702
United States

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