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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)
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Open Access Gold
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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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Publication type Article: Journal article
Document type Scientific Article
Keywords Pre-messenger-rna; Nf-kappa-b; Gene-expression; Intron Retention; Cross-talk; Transcription; Isoform; Rbm4; Identification; Tissue
ISSN (print) / ISBN 0305-1048
e-ISSN 1362-4962
Quellenangaben Volume: 49, Issue: 18, Pages: 10657–10676 Article Number: , Supplement: ,
Publisher Oxford University Press
Publishing Place Great Clarendon St, Oxford Ox2 6dp, England
Reviewing status Peer reviewed
Grants French Laboratory of Excellence
Ligue contre le Cancer
Institut National de la Santé et de la Recherche Médicale
Deutsche Forschungsgemeinschaft