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You are here: Home / Teams / Regulation of Genome Architecture and Dynamics of Splicing (ReGArDS) - D. Auboeuf and C. Bourgeois / Publications / 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

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

E. Manet, H. Polvèche, F. Mure, P. Mrozek-Gorska, F. Roisné-Hamelin, W. Hammerschmidt, D. Auboeuf, and H. Gruffat (2021)

Nucleic Acids Res, 49(18):10657–10676.

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.

[PubMed Central:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8501971PMC8501971] [DOI:https://dx.doi.org/10.1093/nar/gkab78710.1093/nar/gkab787] [PubMed:https://www.ncbi.nlm.nih.gov/pubmed/1872311318723113]

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