The identification of up-regulated ebv-miR-BHRF1-2-5p targeting MALT1 and ebv-miR-BHRF1-3 in the circulation of patients with multiple sclerosis

Clin Exp Immunol. 2017 Jul;189(1):120-126. doi: 10.1111/cei.12954. Epub 2017 Mar 28.

Abstract

Epstein-Barr virus (EBV) is a well-documented aetiological factor for multiple sclerosis (MS). EBV encodes at least 44 microRNAs (miRNAs) that are readily detectable in the circulation of human. Previous studies have demonstrated that EBV-encoded miRNAs regulate host immune response and may serve as biomarkers for EBV-associated diseases. However, the roles of EBV miRNAs in MS are still unknown. To fill the gap, we conducted a comprehensive profiling of 44 mature EBV miRNAs in 30 relapsing-remitting MS (RRMS) patients at relapse and 30 matched healthy controls. Expression levels of ebv-miR-BHRF1-2-5p and ebv-miR-BHRF1-3 were elevated significantly in the circulation and correlated positively with the expanded disability status scale (EDSS) scores of MS patients. Receiver operating characteristic (ROC) analyses confirmed that the expression of these two miRNAs distinguished MS patients clearly from healthy controls. Luciferase assays revealed that ebv-miR-BHRF1-2-5p may directly target MALT1 (mucosa-associated lymphoid tissue lymphoma transport protein 1), a key regulator of immune homeostasis. In conclusion, we described the expression of EBV miRNAs in MS and preliminarily validated the potential target genes of significantly altered EBV miRNAs. The findings may pave the way for prospective study about the pathogenesis of MS.

Keywords: Epstein-Barr virus; MALT1; microRNA; multiple sclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Case-Control Studies
  • Caspases / genetics*
  • China
  • Epstein-Barr Virus Infections / complications*
  • Female
  • Herpesvirus 4, Human
  • Humans
  • Male
  • MicroRNAs / blood*
  • MicroRNAs / genetics
  • Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein
  • Multiple Sclerosis / blood*
  • Neoplasm Proteins / genetics*
  • Prospective Studies
  • ROC Curve
  • Transcriptional Activation
  • Up-Regulation
  • Viral Proteins / blood*
  • Viral Proteins / genetics
  • Young Adult

Substances

  • BHRF1 protein, Human herpesvirus 4
  • MicroRNAs
  • Neoplasm Proteins
  • Viral Proteins
  • Caspases
  • MALT1 protein, human
  • Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein