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. Issue 18 (16th September 2021)

• Record Type: Journal Article
• Authors: Manet, Evelyne; Polvèche, Hélène; Mure, Fabrice; Mrozek-Gorska, Paulina; Roisné-Hamelin, Florian; Hammerschmidt, Wolfgang; Auboeuf, Didier; Gruffat, Henri
• Is Part Of: Nucleic acids research. Volume 49:Issue 18(2021)
• Page Start: 10657
• Page End: 10676
• Publication Date: 2021-09-16
• Subjects: Nucleic acids -- Periodicals; Molecular biology -- Periodicals; 572.805
• DOI: 10.1093/nar/gkab787
• Languages: English
• ISSNs: 0305-1048

Abstract

Abstract: 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 .