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BALF0\/1 subverted caveolin-mediated endocytosis to internalize PM BCR complexes and to deliver them to the endoplasmic reticulum. BALF0\/1 stimulated immunoglobulin HC cytoplasmic tail ubiquitination, which together with the ATPase valosin-containing protein\/p97 drove ER-associated degradation of BCR complexes by cytoplasmic proteasomes. BALF0\/1 knockout reduced the viral load of secreted EBV particles from B cells that expressed a monoclonal antibody against EBV glycoprotein 350 but not a control anti-influenza hemagglutinin antibody and increased viral particle immunoglobulin incorporation. Consistent with downmodulation of PM BCR, BALF0\/1 overexpression reduced viability of a diffuse large B cell lymphoma cell line whose survival is dependent upon BCR signaling. Collectively, our results suggest that EBV BALF0\/1 downmodulates immunoglobulin upon lytic reactivation to block BCR signaling and support virion release, but await the development of suitable models to test its roles in EBV reactivation in vivo.<\/jats:p>","DOI":"10.1073\/pnas.2400167122","type":"journal-article","created":{"date-parts":[[2025,1,23]],"date-time":"2025-01-23T11:15:58Z","timestamp":1737630958000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":8,"title":["Epstein\u2013Barr virus BALF0\/1 subverts the Caveolin and ERAD pathways to target B cell receptor complexes for degradation"],"prefix":"10.1073","volume":"122","author":[{"given":"Stephanie Pei Tung","family":"Yiu","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Brigham and Women\u2019s Hospital","place":["Boston"]},{"name":"Harvard Graduate Program in Virology","place":["Boston"]},{"name":"Center for 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