Afrasiabi Ali, Fewings Nicole L, Schibeci Stephen D, Keane Jeremy T, Booth David R, Parnell Grant P, Swaminathan Sanjay
Systems Biology and Health Data Analytics Lab, The Graduate School of Biomedical Engineering, UNSW Sydney, Sydney, NSW 2052, Australia.
EBV Molecular Lab, Centre for Immunology and Allergy Research, Westmead Institute for Medical Research, University of Sydney, Westmead, NSW 2145, Australia.
Int J Mol Sci. 2021 Mar 13;22(6):2927. doi: 10.3390/ijms22062927.
Although the causes of Multiple Sclerosis (MS) still remain largely unknown, multiple lines of evidence suggest that (EBV) infection may contribute to the development of MS. Here, we aimed to identify the potential contribution of EBV-encoded and host cellular miRNAs to MS pathogenesis. We identified differentially expressed host miRNAs in EBV infected B cells (LCLs) and putative host/EBV miRNA interactions with MS risk loci. We estimated the genotype effect of MS risk loci on the identified putative miRNA:mRNA interactions in silico. We found that the protective allele of MS risk SNP rs4808760 reduces the expression of . In addition, our analysis suggests that may interact with differently in LCLs compared to B cells. In vitro assays indicated that the protective allele of MS risk SNP rs10271373 increases expression in LCLs, but not in B cells. The higher expression for the protective allele in LCLs is consistent with increased response via and so decreased immune evasion by EBV. Taken together, this provides evidence that EBV infection dysregulates the B cell miRNA machinery, including MS risk miRNAs, which may contribute to MS pathogenesis via interaction with MS risk genes either directly or indirectly.
尽管多发性硬化症（MS）的病因在很大程度上仍不明确，但多条证据表明，爱泼斯坦-巴尔病毒（EBV）感染可能促使MS的发生。在此，我们旨在确定EBV编码的和宿主细胞的微小RNA（miRNA）对MS发病机制的潜在作用。我们在EBV感染的B细胞（淋巴母细胞系，LCLs）中鉴定出差异表达的宿主miRNA以及与MS风险位点的假定宿主/EBV miRNA相互作用。我们在计算机模拟中估计了MS风险位点对所鉴定的假定miRNA:mRNA相互作用的基因型效应。我们发现MS风险单核苷酸多态性（SNP）rs4808760的保护性等位基因降低了……的表达。此外，我们的分析表明，……与……在LCLs中的相互作用可能与在B细胞中的不同。体外试验表明，MS风险SNP rs10271373的保护性等位基因增加了LCLs中……的表达，但在B细胞中未增加。LCLs中保护性等位基因的较高表达与通过……增加……反应一致，因此EBV的免疫逃逸减少。综上所述，这提供了证据表明EBV感染会使B细胞miRNA机制失调，包括MS风险miRNA，这可能通过直接或间接与MS风险基因相互作用而促成MS发病机制。
