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.

β-冠状病毒是一个正链包膜 RNA 病毒家族，其中包括严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2)。关于它们的细胞进入和复制途径有很多了解，但它们的离开模式仍然不确定。使用成像方法和病毒特异性报告基因，我们证明 β-冠状病毒利用溶酶体运输进行出口，而不是其他包膜病毒更常用的生物合成分泌途径。这种非常规的出口受 Arf 样小 GTPase Arl8b 调节，可以被 Rab7 GTPase 竞争性抑制剂 CID1067700 阻断。β-冠状病毒的这种非裂解释放导致溶酶体脱酸、溶酶体降解酶失活和抗原呈递途径中断。