Detection of JCPyV microRNA in blood and urine samples of multiple sclerosis patients under natalizumab therapy

Abstract

Polyomavirus JC (JCPyV) reactivation and development of progressive multifocal leukoencephalopathy is a health concern in multiple sclerosis patients under natalizumab therapy. Here, the JCPyV microRNA-J1-3p and microRNA-J1-5p expressions and genomic variability were investigated in blood and urine samples of multiple sclerosis patients before and under natalizumab therapy and in healthy controls. The two JCPyV microRNAs were detected in the JCPyV-DNA-positive peripheral blood mononuclear cell samples and in the exosomes derived from plasma and urine obtained from JCPyV-DNA-positive and JCPyV-DNA-negative patients. In particular, the increased JCPyV microRNA expression in samples of multiple sclerosis patients under natalizumab therapy was consistent with the high JCPyV-DNA positivity observed in these samples. Moreover, JCPyV microRNA genomic region showed few nucleotide differences in samples obtained from blood and urine of multiple sclerosis patients and healthy controls. Overall, these data suggest a potential role of the JCPyV microRNA expression in counteracting the viral reactivation to maintain JCPyV asymptomatic persistence in the host.

The JCPYV DNA load inversely correlates with the viral microrna expression in blood and cerebrospinal fluid of patients at risk of PML

“…The expression of JCPyV miRNAs has been reported in different studies, thus confirming the presence of these molecules in PML from brain tissues [7], urine, and blood from healthy subjects, multiple sclerosis patients [12,23], and JCPyV-positive colorectal cancer tissues [24]. The data obtained in the present study suggest a potential role of JCPyV miRNA in viral reactivation.…”

“…In our study, all the specimens from the HIV+ and healthy donors exhibited the archetype NCCR structure, whereas those collected from the PML patients exhibited the pathogenic structure (rearranged NCCR form). Additionally, the sequencing analysis of the miRNA noncoding gene revealed the presence of three different mutations located at three hot spots, thus confirming our previous observations [6,12]. In particular, one of these mutated positions is located within the miRNA-5p-expressing region.…”

“…Consequently, a reduction in JCPyV miRNA expression and/or its variability could be relevant for the induction of JCPyV reactivation, the succession of persistence/replication viral processes and the development of PML. Moreover, additional evidence suggests that JCPyV miRNAs, similar to other viral miRNAs, can reside in exosomes (small vesicles secreted from cells for intercellular communication), which suggests that these miRNAs may function outside the infected cell in which they were produced [11,12]. Thus, investigation of miRNAs in exosomes can serve as a new tool for monitoring JCPyV reactivation in the host.…”

A Refined Bead-Free Method to Identify Astrocytic Exosomes in Primary Glial Cultures and Blood Plasma

“…Experimental evidence for a contributing role of exosomes to the progression of multiple sclerosis is currently limited, yet studies identifying the presence of extracellular vesicles in numerous body fluids including cerebrospinal fluid (Scolding et al, 1989), blood (Minagar et al, 2001), and urine (Giovannelli et al, 2015). The findings suggest that monitoring of CNS-derived extracellular vesicles, including exosomes, may offer utility for monitoring disease progression and/or responsiveness of MS patients to therapies.…”

“…Beyond a potential therapeutic use of exosomes in MS, there is evidence for their use a diagnostic marker in patients receiving treatments. miRNA species have been detected in the blood and urine of MS patients undergoing natalizumab therapy (Giovannelli et al, 2015). …”