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.

doi:10.1101/2020.07.25.192310

bioRxiv · 10.1101/2020.07.25.192310

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.

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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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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.. 2020-07-25. β-Coronaviruses use lysosomal organelles for cellular egress.. https://doi.org/10.1101/2020.07.25.192310

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