Evidence from genome wide association studies implicates reduced control of Epstein-Barr virus infection in multiple sclerosis susceptibility

Autor: Monica A. I. Basuki, David Brown, Nicole Fewings, Grant P Parnell, David R. Booth, Stephen D. Schibeci, Graeme J. Stewart, Sanjay Swaminathan, Bruce V. Taylor, Yuan Zhou, Ali Afrasiabi, Fiona C. McKay, Ramya Chandramohan
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Herpesvirus 4
Human
lcsh:QH426-470
Quantitative Trait Loci
lcsh:Medicine
Genome-wide association study
Single-nucleotide polymorphism
Biology
medicine.disease_cause
Virus Replication
Expression quantitative trait loci
Polymorphism
Single Nucleotide
Multiple sclerosis
03 medical and health sciences
0302 clinical medicine
hemic and lymphatic diseases
Genotype
medicine
Transcription factors
Genetics
Humans
Epstein-Barr virus
Memory B cell
Molecular Biology
Gene
Genetics (clinical)
Cells
Cultured
miRNA
B-Lymphocytes
TNF Receptor-Associated Factor 3
Research
lcsh:R
Endonucleases
Phenotype
Epstein–Barr virus
3. Good health
Virus Latency
lcsh:Genetics
030104 developmental biology
030220 oncology & carcinogenesis
Immunology
CD4 Antigens
Molecular Medicine
Transcriptome
Risk genes
Zdroj: Genome Medicine, Vol 11, Iss 1, Pp 1-13 (2019)
Genome Medicine
Popis: Background Genome wide association studies have identified > 200 susceptibility loci accounting for much of the heritability of multiple sclerosis (MS). Epstein-Barr virus (EBV), a memory B cell tropic virus, has been identified as necessary but not sufficient for development of MS. The molecular and immunological basis for this has not been established. Infected B cell proliferation is driven by signalling through the EBV produced cell surface protein LMP1, a homologue of the MS risk gene CD40. Methods We have investigated transcriptomes of B cells and EBV-infected B cells at Latency III (LCLs) and identified MS risk genes with altered expression on infection and with expression levels associated with the MS risk genotype (LCLeQTLs). The association of LCLeQTL genomic burden with EBV phenotypes in vitro and in vivo was examined. The risk genotype effect on LCL proliferation with CD40 stimulation was assessed. Results These LCLeQTL MS risk SNP:gene pairs (47 identified) were over-represented in genes dysregulated between B and LCLs (p
Databáze: OpenAIRE
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