β-Coronaviruses Use Lysosomal Organelles for Cellular Egress

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.