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 include the severe acute respiratory syndrome-CoV2 (SARS-CoV2). 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-Coronavirus results in lysosome deacidification, inactivation of lysosomal degradation enzymes and disruption of antigen presentation pathways. The 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.

Highlights

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  β-Coronaviruses do not use the biosynthetic secretory pathway to egress.

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  β-Coronaviruses traffic to lysosomes; egress by Arl8b-dependent lysosomal exocytosis.

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  Lysosomes are deacidified and proteolytic enzymes inactive in infected cells.

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  Antigen processing and presentation is perturbed in β -Coronavirus infection.

Abstract

Altan-Bonnet 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.