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Beer, S. ; Wange, L.E.* ; Zhang, X. ; Kuklik-Roos, C. ; Enard, W.* ; Hammerschmidt, W. ; Scialdone, A. ; Kempkes, B.

EBNA2-EBF1 complexes promote MYC expression and metabolic processes driving S-phase progression of Epstein-Barr virus-infected B cells.

Proc. Natl. Acad. Sci. U.S.A. 119:e2200512119 (2022)
Verlagsversion Forschungsdaten DOI
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
Epstein-Barr virus (EBV) is a human tumor virus which preferentially infects resting human B cells. Upon infection in vitro, EBV activates and immortalizes these cells. The viral latent protein EBV nuclear antigen 2 (EBNA2) is essential for B cell activation and immortalization; it targets and binds the cellular and ubiquitously expressed DNA-binding protein CBF1, thereby transactivating a plethora of viral and cellular genes. In addition, EBNA2 uses its N-terminal dimerization (END) domain to bind early B cell factor 1 (EBF1), a pioneer transcription factor specifying the B cell lineage. We found that EBNA2 exploits EBF1 to support key metabolic processes and to foster cell cycle progression of infected B cells in their first cell cycles upon activation. The α1-helix within the END domain was found to promote EBF1 binding. EBV mutants lacking the α1-helix in EBNA2 can infect and activate B cells efficiently, but activated cells fail to complete the early S phase of their initial cell cycle. Expression of MYC, target genes of MYC and E2F, as well as multiple metabolic processes linked to cell cycle progression are impaired in EBVΔα1-infected B cells. Our findings indicate that EBF1 controls B cell activation via EBNA2 and, thus, has a critical role in regulating the cell cycle of EBV-infected B cells. This is a function of EBF1 going beyond its well-known contribution to B cell lineage specification.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter B Cell Activation ; Epstein-barr Virus ; Myc Expression ; Rna Sequencing ; Transcription Factor
ISSN (print) / ISBN 0027-8424
e-ISSN 1091-6490
Quellenangaben Band: 119, Heft: 30, Seiten: , Artikelnummer: e2200512119 Supplement: ,
Verlag National Academy of Sciences
Begutachtungsstatus Peer reviewed
Förderungen Deutsche Forschungsgemeinschaft (DFG)