β-Coronaviruses Use Lysosomes for Egress Instead of the Biosynthetic Secretory Pathway

Sourish Ghosh; Teegan A Dellibovi-Ragheb; Adeline Kerviel; Eowyn Pak; Qi Qiu; Matthew Fisher; Peter M Takvorian; Christopher Bleck; Victor W Hsu; Anthony R Fehr; Stanley Perlman; Sooraj R Achar; Marco R Straus; Gary R Whittaker; Cornelis A M de Haan; John Kehrl; Grégoire Altan-Bonnet; Nihal Altan-Bonnet

doi:10.1016/j.cell.2020.10.039

β-Coronaviruses Use Lysosomes for Egress Instead of the Biosynthetic Secretory Pathway

Sourish Ghosh, Teegan A Dellibovi-Ragheb, Adeline Kerviel, Eowyn Pak, Qi Qiu, Matthew Fisher, Peter M Takvorian, Christopher Bleck, Victor W Hsu, Anthony R Fehr, Stanley Perlman, Sooraj R Achar, Marco R Straus, Gary R Whittaker, Cornelis A M de Haan, John Kehrl, Grégoire Altan-Bonnet, Nihal Altan-Bonnet

Virology

Laboratory of Host-Pathogen Dynamics, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Federated Department of Biological Sciences, Rutgers-State University of New Jersey, Newark, NJ, USA.
Electron Microscopy Core Facility, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Division of Rheumatology, Inflammation and Immunity, Brigham and Women's Hospital, Department of Medicine, Harvard Medical School, Boston, MA, USA.
Department of Microbiology and Immunology, University of Iowa, Iowa City, IA, USA.
lmmunodynamics Group - Laboratory of Integrative Cancer Immunology, National Cancer Institute, Bethesda, MD, USA.
Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.
B-Cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
lmmunodynamics Group - Laboratory of Integrative Cancer Immunology, National Cancer Institute, Bethesda, MD, USA. Electronic address: [email protected].
Laboratory of Host-Pathogen Dynamics, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address: [email protected].

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Pages (from-to)	1520-1535.e14
Journal	Cell
Volume	183
Issue number	6
Early online date	2020
DOIs	https://doi.org/10.1016/j.cell.2020.10.039
Publication status	Published - 10 Dec 2020

Keywords

coronavirus
SARS-CoV-2
viral egress
lysosome
pH
viral immunology
antigen presentation
acidification/deacidification ARL8b
Rab7
CD1067700

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10.1016/j.cell.2020.10.039

1-s2.0-S009286742031446X-mainFinal published version, 9.31 MBLicence: Taverne

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Ghosh, S., Dellibovi-Ragheb, T. A., Kerviel, A., Pak, E., Qiu, Q., Fisher, M., Takvorian, P. M., Bleck, C., Hsu, V. W., Fehr, A. R., Perlman, S., Achar, S. R., Straus, M. R., Whittaker, G. R., de Haan, C. A. M., Kehrl, J., Altan-Bonnet, G., & Altan-Bonnet, N. (2020). β-Coronaviruses Use Lysosomes for Egress Instead of the Biosynthetic Secretory Pathway. Cell, 183(6), 1520-1535.e14. https://doi.org/10.1016/j.cell.2020.10.039

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title = "β-Coronaviruses Use Lysosomes for Egress Instead of the Biosynthetic Secretory Pathway",

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.",

keywords = "coronavirus, SARS-CoV-2, viral egress, lysosome, pH, viral immunology, antigen presentation, acidification/deacidification ARL8b, Rab7, CD1067700",

author = "Sourish Ghosh and Dellibovi-Ragheb, \{Teegan A\} and Adeline Kerviel and Eowyn Pak and Qi Qiu and Matthew Fisher and Takvorian, \{Peter M\} and Christopher Bleck and Hsu, \{Victor W\} and Fehr, \{Anthony R\} and Stanley Perlman and Achar, \{Sooraj R\} and Straus, \{Marco R\} and Whittaker, \{Gary R\} and \{de Haan\}, \{Cornelis A M\} and John Kehrl and Gr{\'e}goire Altan-Bonnet and Nihal Altan-Bonnet",

note = "Published by Elsevier Inc.",

year = "2020",

month = dec,

day = "10",

doi = "10.1016/j.cell.2020.10.039",

language = "English",

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Ghosh, S, Dellibovi-Ragheb, TA, Kerviel, A, Pak, E, Qiu, Q, Fisher, M, Takvorian, PM, Bleck, C, Hsu, VW, Fehr, AR, Perlman, S, Achar, SR, Straus, MR, Whittaker, GR, de Haan, CAM, Kehrl, J, Altan-Bonnet, G & Altan-Bonnet, N 2020, 'β-Coronaviruses Use Lysosomes for Egress Instead of the Biosynthetic Secretory Pathway', Cell, vol. 183, no. 6, pp. 1520-1535.e14. https://doi.org/10.1016/j.cell.2020.10.039

TY - JOUR

T1 - β-Coronaviruses Use Lysosomes for Egress Instead of the Biosynthetic Secretory Pathway

AU - Ghosh, Sourish

AU - Dellibovi-Ragheb, Teegan A

AU - Kerviel, Adeline

AU - Pak, Eowyn

AU - Qiu, Qi

AU - Fisher, Matthew

AU - Takvorian, Peter M

AU - Bleck, Christopher

AU - Hsu, Victor W

AU - Fehr, Anthony R

AU - Perlman, Stanley

AU - Achar, Sooraj R

AU - Straus, Marco R

AU - Whittaker, Gary R

AU - de Haan, Cornelis A M

AU - Kehrl, John

AU - Altan-Bonnet, Grégoire

AU - Altan-Bonnet, Nihal

N1 - Published by Elsevier Inc.

PY - 2020/12/10

Y1 - 2020/12/10

N2 - 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.

AB - 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.

KW - coronavirus

KW - SARS-CoV-2

KW - viral egress

KW - lysosome

KW - pH

KW - viral immunology

KW - antigen presentation

KW - acidification/deacidification ARL8b

KW - Rab7

KW - CD1067700

U2 - 10.1016/j.cell.2020.10.039

DO - 10.1016/j.cell.2020.10.039

M3 - Article

C2 - 33157038

SN - 0092-8674

VL - 183

SP - 1520-1535.e14

JO - Cell

JF - Cell

IS - 6

ER -

β-Coronaviruses Use Lysosomes for Egress Instead of the Biosynthetic Secretory Pathway

Abstract

Keywords

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