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bioRxiv · 10.1101/2021.06.30.450614

Exploitation of the Secretory Pathway by SARS-CoV-2 Envelope

Pearson, G. J.·Broncel, M.·Snijders, A. P.·Carlton, J. G.
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Abstract

The {beta}-coronavirus SARS-CoV-2 is the causative agent of the global Covid-19 pandemic. Coronaviral Envelope (E) proteins are pentameric viroporins that play essential roles in assembly, release and pathogenesis. We developed an inert tagging strategy for SARS-CoV-2 E and find that it localises to the Golgi and to lysosomes. We identify sequences in E, conserved across Coronaviridae, responsible for ER-to-Golgi export, and relate this activity to interaction with COP-II via SEC24. Using proximity biotinylation, we identify host-cell factors that interact with E and identify an ARFRP1/AP-1 dependent pathway allowing Golgi-to-lysosome trafficking of E. We identify sequences in E that bind AP-1, are conserved across {beta}-coronaviruses and allow E to be trafficked from Golgi to lysosomes. We show that E acts to deacidify lysosomes and by developing a trans-complementation assay, we show that both lysosomal trafficking of E and its viroporin activity are necessary for efficient viral replication and release.

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Pearson, G. J., Broncel, M., Snijders, A. P., Carlton, J. G.. 2021-06-30. Exploitation of the Secretory Pathway by SARS-CoV-2 Envelope. https://doi.org/10.1101/2021.06.30.450614

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