CAPRIN1 localizes to CD63-positive MVB-like SARS-CoV-2 egress compartments and limits cytopathic effects
Year: 2026
Type: preprint
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.
Institutions: Medizinische Hochschule Hannover, German Center for Infection Research, Centre for Structural Systems Biology, Leibniz Institute of Virology (LIV), Deutsches Elektronen-Synchrotron DESY, University of Lübeck, University Medical Center Hamburg-Eppendorf, Bernhard Nocht Institute for Tropical Medicine
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G1629420513, G1885170266, G1925557638, G2122232498, G2857655130, G339059223, G3445821997, G3656803931, FOR 5200: Disrupt Evade Exploit: Steuerung der Genexpression und Wirtsantwort durch DNA Viren (DEEPDV), GRK 2771: Mensch und Mikrobe: Reorganisation von Zellkompartimenten und Molekülkomplexen während der Infektion, G4068377905, G4088248013, EXC 2155: RESIST Resolving Infection Susceptibility, G4455854446, G4466016162, Timestamping Integrative Approach to Understand Secondary Envelopment of Human Cytomegalovirus, G5186833673, G526414218, G5397013247, G5668050127, GRK 2887: VISualisierung und Struktur in der viralen InfektION (VISION), G6309922372, G6387682778, G6781976155, G7786665414, G8084454587, G8693764584
OpenAlex ID: W7204275162