First Author | Ghosh S | Year | 2020 |
Journal | Cell | Volume | 183 |
Issue | 6 | Pages | 1520-1535.e14 |
PubMed ID | 33157038 | Mgi Jnum | J:302472 |
Mgi Id | MGI:6508519 | Doi | 10.1016/j.cell.2020.10.039 |
Citation | Ghosh S, et al. (2020) beta-Coronaviruses Use Lysosomes for Egress Instead of the Biosynthetic Secretory Pathway. Cell 183(6):1520-1535.e14 |
abstractText | beta-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 beta-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 beta-coronaviruses results in lysosome deacidification, inactivation of lysosomal degradation enzymes, and disruption of antigen presentation pathways. beta-Coronavirus-induced exploitation of lysosomal organelles for egress provides insights into the cellular and immunological abnormalities observed in patients and suggests new therapeutic modalities. |