The interaction of Multiple Sclerosis risk loci with Epstein-Barr virus phenotypes implicates the virus in pathogenesis
The interaction of Multiple Sclerosis risk loci with Epstein-Barr virus phenotypes implicates the virus in pathogenesis
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DOI：
10.1038/s41598-019-55850-z
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发表时间：
2020-01-13
影响因子：
4.6
通讯作者：
Booth, David R.
中科院分区：
文献类型：
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作者：
Afrasiabi, Ali;Parnell, Grant P.;Booth, David R.
将全基因组关联研究（GWAS）的发现转化为新的治疗方法，需要识别相关的免疫学背景，以询问遗传效应。在一个最大的GWAS中，超过200个风险位点被确定为多发性硬化症（MS）易感性。感染eb病毒（EBV）似乎是发展多发性硬化症（MS）的必要条件。在EBV感染的B细胞（LCLs）中，许多MS风险位点与基因表达改变有关。我们研究了这一免疫学背景，以确定MS风险位点与EBV DNA拷贝数、内在生长速率和EBV编码miRNA表达之间的相互作用。与其他疾病或性状相比，EBV DNA拷贝数与MS风险等位基因的关联显著增加。EBV mirna BART4-3p和BART3-5p与EBV DNA拷贝数和MS危险位点高度相关。脊髓灰质炎病毒受体（PVR）风险SNP与EBV DNA拷贝数、PVR和miRNA表达相关。针对EBV miRNAs BART4-3p和BART3-5p以及PVR基因，可能会为ms提供治疗益处。该研究还表明，如何利用免疫学背景和风险位点相互作用来验证和开发新的治疗方法。
Translating the findings of genome wide association studies (GWAS) to new therapies requires identification of the relevant immunological contexts to interrogate for genetic effects. In one of the largest GWAS, more than 200 risk loci have been identified for Multiple Sclerosis (MS) susceptibility. Infection with Epstein-Barr virus (EBV) appears to be necessary for the development of Multiple Sclerosis (MS). Many MS risk loci are associated with altered gene expression in EBV infected B cells (LCLs). We have interrogated this immunological context to identify interaction between MS risk loci and EBV DNA copy number, intrinsic growth rate and EBV encoded miRNA expression. The EBV DNA copy number was associated with significantly more risk alleles for MS than for other diseases or traits. EBV miRNAs BART4-3p and BART3-5p were highly associated with EBV DNA copy number and MS risk loci. The poliovirus receptor (PVR) risk SNP was associated with EBV DNA copy number, PVR and miRNA expression. Targeting EBV miRNAs BART4-3p and BART3-5p, and the gene PVR, may provide therapeutic benefit in MS. This study also indicates how immunological context and risk loci interactions can be exploited to validate and develop novel therapeutic approaches.