β-Coronaviruses use lysosomal organelles for cellular egress.
Altan-Bonnet, N.; Altan-Bonnet, G. Y.; Ghosh, S.; Dellibovi-Ragheb, T.; Pak, E.; Qiu, Q.; Fisher, M.; Takvorian, P.; Bleck, C.; Hsu, V.; Fehr, A.; Perlman, S.; Straus, M.; Whittaker, G.; de Haan, C. A.
10.1101/2020.07.25.192310 bioRxivShow abstract
{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 demonstrate 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.
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