Profiling of Epstein-Barr Virus microRNAs in Whole Blood and Exosomes in Multiple Sclerosis.

BACKGROUND

Multiple sclerosis (MS) is a neuroinflammatory, demyelinating disease with Epstein-Barr virus (EBV) suggested as a prerequisite for disease development. EBV expresses 44 microRNAs (miRNAs) with largely unknown functions, but they have been implicated in EBV-infected cell proliferation and immune evasion.

OBJECTIVES

This study investigates EBV miRNAs levels in whole blood and plasma exosomes at baseline and after treatment, and in relation to disease activity based on age-adjusted NfL ratios, in 50 newly diagnosed patients with relapsing-remitting MS (RRMS).

METHODS

EBV miRNAs purified from whole blood and isolated plasma exosomes were measured by qPCR, using TaqMan Array Cards, and correlated to mRNA of , , , , , , and in whole blood, measured by qPCR. Serum neurofilament light chain (NfL) and IL-6, plasma anti-EBNA1 antibody titers, occludin, and zonula occludens-1 were measured by various immunoassays.

RESULTS

The miRNA profiling of whole blood revealed expression of BHRF1 miRNAs in most patients, indicating that EBV is in lytic phase or latency phase III. Higher levels of miR-BART14-3p were observed in patients classified with high disease activity. EBV miRNA levels correlated with anti-EBNA1 antibody titers, biomarkers of inflammation and tight junction proteins.