Dynamics of viral infection

乙型冠状病毒是包括严重急性呼吸综合征-CoV2(SARS-CoV2)在内的一类正链包膜RNA病毒。虽然关于它们的细胞进入和复制途径已知很多，但它们的出口方式仍然不确定；然而，与其他包膜病毒类似，这被认为是通过生物合成的分泌途径实现的。使用成像方法结合病毒特异性报道，我们证明了贝塔冠状病毒利用溶酶体转运从细胞中排出。该途径受Arf样小GTP酶Ar18b的调节，因此，病毒出口对生物合成分泌途径的抑制剂不敏感。冠状病毒感染导致溶酶体脱酸、溶酶体降解失活和抗原提呈途径中断。这种冠状病毒诱导的溶酶体利用提供了对患者观察到的细胞和免疫异常的洞察，并提出了新的治疗方法。

Beta-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 demonstrated that beta-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.