Human endogenous retrovirus (HERV) are the present day versions of retroviral germline infections that have occured millions of years ago, which occupy about 8 % of the genome [1]. While they are mostly replication deficient, they are known to express RNA and protein [2] during particular developmental stages, or as a response to aging [3], inflammation and a wide range of pathologies [4]. A human retrovirus discovered in Multiple Sclerosis (MS) patients [5], turned out to be the prototype of a novel HERV family referred to as HERVW [6]. The HERV W family consists of 213 elements, 12 out of which are complete proviral copies with intact LTRs [7]. Increased expression of HERVW in peripheral blood mononuclear cells (PBMCs) has been repeatedly associated with MS, and the presence of HERVW protein or elevated RNA transcription has been correlated with disease activity [8– 10]. While a contribution of HERVW-encoded proteins to brain disease is suggested by their presence in MSassociated brain lesions, expression in peripheral organs may be involved in the disease process through cytokineinduced damage to the blood brain barrier and subsequent infiltration of monocytes. Alterations in peripheral expression may also serve as a useful and practical marker for the diagnostics of this CNS disease. Therefore, we quantified overall HERVW levels and identified individual HERVW loci actually transcribed in PBMCs. Analysis was carried out in patients diagnosed with Clinically Isolated Syndrome (CIS), a precursor to MS, defined by a single episode of neurologic symptoms lasting at least 24 h. CIS is an indicator of future development of MS, as 60 % of the people diagnosed with CIS develop MS [11]. These patients potentially represent the earliest stage of MS routinely available for clinical analysis. We undertook a Next Generation Sequencing (NGS)-based analysis of transcripts amplified from cDNA obtained from patients with CIS and samples from healthy controls. Data presented from this pilot experiment indicate that the relative frequency of specific HERVW copies is altered in PBMC of CIS patients, even in the absence of overall HERVW overexpression. Such altered frequency appears to be derived from less abundantly transcribed but potentially MSrelated HERVW loci.
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