Expression of HERV-Fc1, a Human Endogenous Retrovirus, Is Increased in Patients with Active Multiple Sclerosis

Abstract

Multiple sclerosis (MS) is considered to be an autoimmune disease with an unknown cause and with immune system dysregulation. Among environmental factors, viruses are most often connected with the etiology of MS. Human endogenous retroviruses (HERVs) constitute 5 to 8% of human genomic DNA and have been detected as transcripts and proteins in the central nervous system (CNS) and peripheral blood, frequently in the context of neuroinflammation. HERV-Fc1, which belongs to the HERV-H/F family, has received our attention largely because of the genetic association with MS. We studied the expression of a capsid (Gag) protein of HERV-H/F origin by flow cytometry in peripheral blood mononuclear cells (PBMCs) from healthy controls and from MS patients with nonactive or active disease. There was a significant increase in HERV-H/F Gag expression in CD4 ؉ (P < 0.001) and CD8 ؉ (P < 0.001) T lymphocytes and in monocytes (P ‫؍‬ 0.0356) in PBMCs from MS patients with active disease. Furthermore, we have undertaken the first rigorous SYBR green-based absolute quantitative PCR (Q-PCR) evaluation approach to quantify extracellular HERV-Fc1 RNA viral loads in plasma from MS patients and healthy controls. We found a 4-fold increase in extracellular HERV-Fc1 RNA titers in patients with active MS compared with healthy controls (P < 0.001). These findings strengthen the link between HERV-Fc1 and the pathology of MS. The cause and biological consequences of these differential expression levels will be the subject of further investigation. HERV-Fc1 biology could be a compelling area for understanding the pathology of MS and possibly other autoimmune disorders.

Multiple sclerosis

“…Recently, Perron et al [25▪] used quantitative PCR and antibody staining to detect and quantify HERV-W multiple sclerosis retrovirus (MSRV) expression in peripheral blood mononuclear cells and tissues obtained from MS patients, thereby demonstrating an association between MS disease and MSRV in comparison to healthy controls. Similar work by Laska et al [31▪] provided further evidence that the RNA titer of HERV-Fc1 was markedly higher in MS patients when compared with healthy controls. A potential mechanism by which HERVs could be involved in MS pathogenesis was proposed by Mameli et al [32▪] in that EBV-activated HERV-W/MSRV/synctin-1 in cells derived from peripheral blood and astrocytes, thereby suggesting that EBV could be an initial trigger for MS and that EBV and HERV-W/MSRV/synctin-1 are the main contributors to MS pathogenesis [32▪].…”

Evolutionary age of repetitive element subfamilies and sensitivity of DNA methylation to airborne pollutants

“…On the other hand, decreased DNA methylation in repetitive elements has been linked with increased transcription and higher rates of retrotransposon activity in vitro [14,15]. In human studies, differences in DNA methylation of LINE-1, Alu , and HERV have been consistently demonstrated in response to stress [16] and infections [17], as well as in autoimmune diseases [18], cardiovascular diseases [19] and cancers [20,21]. …”

Synergy of two human endogenous retroviruses in multiple myeloma

“…It remains to be determined whether we have observed a similar phenomenon. Human retroviral loci and their activity have also been implicated in autoimmunity [23,[31][32][33][34][35][36][37]. One of the viral loci here observed, HERV-Fc1, occurs in some of these.…”