The interaction of Epstein-Barr virus encoded transcription factor EBNA2 with multiple sclerosis risk loci is dependent on the risk genotype

Autor: Jeremy Thomas Keane, Ali Afrasiabi, Stephen Donald Schibeci, Sanjay Swaminathan, Grant Peter Parnell, David Richmond Booth
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: EBioMedicine, Vol 71, Iss , Pp 103572- (2021)
Druh dokumentu: article
ISSN: 2352-3964
DOI: 10.1016/j.ebiom.2021.103572
Popis: Background: Epstein-Barr virus (EBV) infection may be necessary for the development of Multiple sclerosis (MS). Earlier we had identified six MS risk loci that are co-located with binding sites for the EBV transcription factor Epstein-Barr Nuclear Antigen 2 (EBNA2) in EBV-infected B cells (lymphoblastoid cell lines – LCLs). Methods: We used an allele-specific chromatin immunoprecipitation PCR assay to assess EBNA2 allelic preference. We treated LCLs with a peptide inhibitor of EBNA2 (EBNA2-TAT), reasoning that inhibiting EBNA2 function would alter gene expression at these loci if it was mediated by EBNA2. Findings: We found that EBNA2 binding was dependent on the risk allele for five of these six MS risk loci (p < 0·05). Treatment with EBNA2-TAT significantly altered the expression of TRAF3 (p < 0·05), CD40 (p < 0·001), CLECL1 (p
Databáze: Directory of Open Access Journals