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Manet, E.* ; Polvèche, H.* ; Mure, F.* ; Mrozek-Gorska, P. ; Roisné-Hamelin, F.* ; Hammerschmidt, W. ; Auboeuf, D.* ; Gruffat, H.*

Modulation of alternative splicing during early infection of human primary B lymphocytes with Epstein-Barr virus (EBV): A novel function for the viral EBNA-LP protein.

Nucleic Acids Res. 49, 10657–10676 (2021)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Epstein-Barr virus (EBV) is a human herpesvirus associated with human cancers worldwide. Ex vivo, the virus efficiently infects resting human B lymphocytes and induces their continuous proliferation. This process is accompanied by a global reprogramming of cellular gene transcription. However, very little is known on the impact of EBV infection on the regulation of alternative splicing, a pivotal mechanism that plays an essential role in cell fate determination and is often deregulated in cancer. In this study, we have developed a systematic time-resolved analysis of cellular mRNA splice variant expression during EBV infection of resting B lymphocytes. Our results reveal that major modifications of alternative splice variant expression appear as early as day 1 post-infection and suggest that splicing regulation provides-besides transcription-an additional mechanism of gene expression regulation at the onset of B cell activation and proliferation. We also report a role for the viral proteins, EBNA2 and EBNA-LP, in the modulation of specific alternative splicing events and reveal a previously unknown function for EBNA-LP-together with the RBM4 splicing factor-in the alternative splicing regulation of two important modulators of cell proliferation and apoptosis respectively, NUMB and BCL-X.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Pre-messenger-rna; Nf-kappa-b; Gene-expression; Intron Retention; Cross-talk; Transcription; Isoform; Rbm4; Identification; Tissue
Sprache englisch
Veröffentlichungsjahr 2021
HGF-Berichtsjahr 2021
ISSN (print) / ISBN 0305-1048
e-ISSN 1362-4962
Zeitschrift Nucleic Acids Research
Quellenangaben Band: 49, Heft: 18, Seiten: 10657–10676 Artikelnummer: , Supplement: ,
Verlag Oxford University Press
Verlagsort Great Clarendon St, Oxford Ox2 6dp, England
Begutachtungsstatus Peer reviewed
Institut(e) Research Unit Gene Vector (AGV)
POF Topic(s) 30203 - Molecular Targets and Therapies
Forschungsfeld(er) Immune Response and Infection
PSP-Element(e) G-501500-001
Förderungen French Laboratory of Excellence
Ligue contre le Cancer
Institut National de la Santé et de la Recherche Médicale
Deutsche Forschungsgemeinschaft
DOI 10.1093/nar/gkab787
WOS ID WOS:000715870700036
Scopus ID 85118285924
PubMed ID 34530456
Erfassungsdatum 2021-10-18
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