2. Academic Validation
  3. β-Coronaviruses Use Lysosomes for Egress Instead of the Biosynthetic Secretory Pathway

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

  • Cell. 2020 Dec 10;183(6):1520-1535.e14. doi: 10.1016/j.cell.2020.10.039.
Sourish Ghosh 1,  Teegan A Dellibovi-Ragheb 1,  Adeline Kerviel 1,  Eowyn Pak 1,  Qi Qiu 1,  Matthew Fisher 1,  Peter M Takvorian 2,  Christopher Bleck 3,  Victor W Hsu 4,  Anthony R Fehr 5,  Stanley Perlman 5,  Sooraj R Achar 6,  Marco R Straus 7,  Gary R Whittaker 7,  Cornelis A M de Haan 8,  John Kehrl 9,  Grégoire Altan-Bonnet 10,  Nihal Altan-Bonnet 11
Affiliations

Affiliations

  • 1 Laboratory of Host-Pathogen Dynamics, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
  • 2 Federated Department of Biological Sciences, Rutgers-State University of New Jersey, Newark, NJ, USA.
  • 3 Electron Microscopy Core Facility, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
  • 4 Division of Rheumatology, Inflammation and Immunity, Brigham and Women's Hospital, Department of Medicine, Harvard Medical School, Boston, MA, USA.
  • 5 Department of Microbiology and Immunology, University of Iowa, Iowa City, IA, USA.
  • 6 lmmunodynamics Group - Laboratory of Integrative Cancer Immunology, National Cancer Institute, Bethesda, MD, USA.
  • 7 Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.
  • 8 Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
  • 9 B-Cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • 10 lmmunodynamics Group - Laboratory of Integrative Cancer Immunology, National Cancer Institute, Bethesda, MD, USA. Electronic address: [email protected].
  • 11 Laboratory of Host-Pathogen Dynamics, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address: [email protected].
PMID: 33157038 DOI: 10.1016/j.cell.2020.10.039
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

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

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