1. A single C-terminal residue controls SARS-CoV-2 spike trafficking and incorporation into VLPs.
- Author
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Dey, Debajit, Qing, Enya, He, Yanan, Chen, Yihong, Jennings, Benjamin, Cohn, Whitaker, Singh, Suruchi, Gakhar, Lokesh, Schnicker, Nicholas, Pierce, Brian, Doray, Balraj, Orban, John, Gallagher, Tom, Hasan, S, and Whitelegge, Julian
- Subjects
Humans ,SARS-CoV-2 ,COVID-19 ,Golgi Apparatus ,Spike Glycoprotein ,Coronavirus - Abstract
The spike (S) protein of SARS-CoV-2 is delivered to the virion assembly site in the ER-Golgi Intermediate Compartment (ERGIC) from both the ER and cis-Golgi in infected cells. However, the relevance and modulatory mechanism of this bidirectional trafficking are unclear. Here, using structure-function analyses, we show that S incorporation into virus-like particles (VLP) and VLP fusogenicity are determined by coatomer-dependent S delivery from the cis-Golgi and restricted by S-coatomer dissociation. Although S mimicry of the host coatomer-binding dibasic motif ensures retrograde trafficking to the ERGIC, avoidance of the host-like C-terminal acidic residue is critical for S-coatomer dissociation and therefore incorporation into virions or export for cell-cell fusion. Because this C-terminal residue is the key determinant of SARS-CoV-2 assembly and fusogenicity, our work provides a framework for the export of S protein encoded in genetic vaccines for surface display and immune activation.
- Published
- 2023