Cargando…

The Interaction of Human and Epstein–Barr Virus miRNAs with Multiple Sclerosis Risk Loci

Although the causes of Multiple Sclerosis (MS) still remain largely unknown, multiple lines of evidence suggest that Epstein–Barr virus (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 pathoge...

Descripción completa

Detalles Bibliográficos
Autores principales: Afrasiabi, Ali, Fewings, Nicole L., Schibeci, Stephen D., Keane, Jeremy T., Booth, David R., Parnell, Grant P., Swaminathan, Sanjay
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000127/
https://www.ncbi.nlm.nih.gov/pubmed/33805769
http://dx.doi.org/10.3390/ijms22062927
_version_ 1783670932785594368
author Afrasiabi, Ali
Fewings, Nicole L.
Schibeci, Stephen D.
Keane, Jeremy T.
Booth, David R.
Parnell, Grant P.
Swaminathan, Sanjay
author_facet Afrasiabi, Ali
Fewings, Nicole L.
Schibeci, Stephen D.
Keane, Jeremy T.
Booth, David R.
Parnell, Grant P.
Swaminathan, Sanjay
author_sort Afrasiabi, Ali
collection PubMed
description Although the causes of Multiple Sclerosis (MS) still remain largely unknown, multiple lines of evidence suggest that Epstein–Barr virus (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 hsa-mir-3188-3p. In addition, our analysis suggests that hsa-let-7b-5p may interact with ZC3HAV1 differently in LCLs compared to B cells. In vitro assays indicated that the protective allele of MS risk SNP rs10271373 increases ZC3HAV1 expression in LCLs, but not in B cells. The higher expression for the protective allele in LCLs is consistent with increased IFN response via ZC3HAV1 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.
format Online
Article
Text
id pubmed-8000127
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-80001272021-03-28 The Interaction of Human and Epstein–Barr Virus miRNAs with Multiple Sclerosis Risk Loci Afrasiabi, Ali Fewings, Nicole L. Schibeci, Stephen D. Keane, Jeremy T. Booth, David R. Parnell, Grant P. Swaminathan, Sanjay Int J Mol Sci Article Although the causes of Multiple Sclerosis (MS) still remain largely unknown, multiple lines of evidence suggest that Epstein–Barr virus (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 hsa-mir-3188-3p. In addition, our analysis suggests that hsa-let-7b-5p may interact with ZC3HAV1 differently in LCLs compared to B cells. In vitro assays indicated that the protective allele of MS risk SNP rs10271373 increases ZC3HAV1 expression in LCLs, but not in B cells. The higher expression for the protective allele in LCLs is consistent with increased IFN response via ZC3HAV1 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. MDPI 2021-03-13 /pmc/articles/PMC8000127/ /pubmed/33805769 http://dx.doi.org/10.3390/ijms22062927 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Afrasiabi, Ali
Fewings, Nicole L.
Schibeci, Stephen D.
Keane, Jeremy T.
Booth, David R.
Parnell, Grant P.
Swaminathan, Sanjay
The Interaction of Human and Epstein–Barr Virus miRNAs with Multiple Sclerosis Risk Loci
title The Interaction of Human and Epstein–Barr Virus miRNAs with Multiple Sclerosis Risk Loci
title_full The Interaction of Human and Epstein–Barr Virus miRNAs with Multiple Sclerosis Risk Loci
title_fullStr The Interaction of Human and Epstein–Barr Virus miRNAs with Multiple Sclerosis Risk Loci
title_full_unstemmed The Interaction of Human and Epstein–Barr Virus miRNAs with Multiple Sclerosis Risk Loci
title_short The Interaction of Human and Epstein–Barr Virus miRNAs with Multiple Sclerosis Risk Loci
title_sort interaction of human and epstein–barr virus mirnas with multiple sclerosis risk loci
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000127/
https://www.ncbi.nlm.nih.gov/pubmed/33805769
http://dx.doi.org/10.3390/ijms22062927
work_keys_str_mv AT afrasiabiali theinteractionofhumanandepsteinbarrvirusmirnaswithmultiplesclerosisriskloci
AT fewingsnicolel theinteractionofhumanandepsteinbarrvirusmirnaswithmultiplesclerosisriskloci
AT schibecistephend theinteractionofhumanandepsteinbarrvirusmirnaswithmultiplesclerosisriskloci
AT keanejeremyt theinteractionofhumanandepsteinbarrvirusmirnaswithmultiplesclerosisriskloci
AT boothdavidr theinteractionofhumanandepsteinbarrvirusmirnaswithmultiplesclerosisriskloci
AT parnellgrantp theinteractionofhumanandepsteinbarrvirusmirnaswithmultiplesclerosisriskloci
AT swaminathansanjay theinteractionofhumanandepsteinbarrvirusmirnaswithmultiplesclerosisriskloci
AT afrasiabiali interactionofhumanandepsteinbarrvirusmirnaswithmultiplesclerosisriskloci
AT fewingsnicolel interactionofhumanandepsteinbarrvirusmirnaswithmultiplesclerosisriskloci
AT schibecistephend interactionofhumanandepsteinbarrvirusmirnaswithmultiplesclerosisriskloci
AT keanejeremyt interactionofhumanandepsteinbarrvirusmirnaswithmultiplesclerosisriskloci
AT boothdavidr interactionofhumanandepsteinbarrvirusmirnaswithmultiplesclerosisriskloci
AT parnellgrantp interactionofhumanandepsteinbarrvirusmirnaswithmultiplesclerosisriskloci
AT swaminathansanjay interactionofhumanandepsteinbarrvirusmirnaswithmultiplesclerosisriskloci