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bioRxiv · 10.64898/2026.08.25.746949

CAPRIN1 localizes to CD63-positive MVB-like SARS-CoV-2 egress compartments and limits cytopathic effects

Woloszyn, J. S.·Schroeder, J.·Berger, J. M.·Kotova, E.·Schaeper, R.·Pfefferle, S.·Uetrecht, C.·Soh, T. K.·Bosse, J. B.
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Abstract

Stress granules (SGs) are cytoplasmic condensates that assemble under cellular stress, including viral infection. The best-characterized evasion strategy in SARS-CoV-2 infection involves the viral nucleocapsid (N) protein hijacking the SG core protein G3BP1, thereby preventing SG assembly. By performing network analysis of N protein interactomes, we identified CAPRIN1 as an underexplored candidate, despite its central role alongside G3BP1 in SG assembly. Here, we provide the first high-resolution spatial and functional data on CAPRIN1 in SARS-CoV-2 infection. Using ultrastructure expansion microscopy (U-ExM), we localized CAPRIN1 and viral egress markers to enlarged, CD63- and LAMP1-positive, multivesicular body (MVB)-like egress compartments, refining the current model of SARS-CoV-2 egress. CAPRIN1 was found on both the limiting membrane of these compartments and within the intraluminal vesicles, a pattern distinct from G3BP1. Knockout of CAPRIN1 increased infection-associated cell death, promoted an aberrant cell-death phenotype, and enhanced syncytia formation. Together, our data reveal distinct activities of CAPRIN1 during infection and identify the egress compartments as MVB-like, raising the possibility that SARS-CoV-2 repurposes more than one cellular pathway for egress.

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Woloszyn, J. S., Schroeder, J., Berger, J. M., Kotova, E., Schaeper, R., Pfefferle, S., Uetrecht, C., Soh, T. K., Bosse, J. B.. 2026-08-26. CAPRIN1 localizes to CD63-positive MVB-like SARS-CoV-2 egress compartments and limits cytopathic effects. https://doi.org/10.64898/2026.08.25.746949

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