β-Coronaviruses Use Lysosomes for Egress Instead of the Biosynthetic Secretory Pathway
Journal
Cell
Journal Volume
183
Journal Issue
6
Pages
1520-153500000000000000
Date Issued
2020
Author(s)
Ghosh S
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. ? 2020Ghosh 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. ? 2020
Subjects
cathepsin D; cid 1067700; glucose regulated protein 78; guanosine triphosphatase; guanosine triphosphatase Arl8b; major histocompatibility antigen class 1; protein inhibitor; T lymphocyte receptor; unclassified drug; adenosine diphosphate ribosylation factor; ARL8B protein, human; Arl8B protein, mouse; CID1067700; fused heterocyclic rings; Rab protein; Rab7 protein; thiourea; acidification; Article; biosynthetic secretory pathway; controlled study; deacidification; endosome; exocytosis; human; immunoelectron microscopy; lysosome; nonhuman; priority journal; real time polymerase chain reaction; secretory pathway; Severe acute respiratory syndrome coronavirus 2; total internal reflection fluorescence microscopy; transmission electron microscopy; animal; drug therapy; female; HeLa cell line; lysosome; metabolism; mouse; pathology; virus release; ADP-Ribosylation Factors; Animals; COVID-19; Female; HeLa Cells; Heterocyclic Compounds, 2-Ring; Humans; Lysosomes; Mice; rab GTP-Binding Proteins; SARS-CoV-2; Secretory Pathway; Thiourea; Virus Release
SDGs
Type
journal article