The DNA Copy Number of Human Endogenous Retrovirus-W (MSRV-Type) Is Increased in Multiple Sclerosis Patients and Is Influenced by Gender and Disease Severity

Abstract

BackgroundMultiple Sclerosis is an autoimmune disease more prevalent in women than in men. Multiple Sclerosis Associated Retrovirus element (MSRV) is a member of type-W endogenous retrovirus family (HERV-W), known to be associated to MS. Most HERVs are unable to replicate but MSRV expression associated with reverse-transcriptase activity in MS would explain reported DNA copy number increase in MS patients. A potential link between HERV-W copies on chromosome X and gender differential prevalence has been suggested. The present study addresses MSRV-type DNA load in relation with the gender differences and clinical status in MS and healthy controls.Results178 MS patients (62.9% women) and 124 controls (56.5% women) were included. MSRV env load (copies/pg of DNA) was analyzed by real time qPCR with specific primers and probe for its env gene, in DNA from peripheral blood mononuclear cells (PBMCs). MSRV load was more elevated in MS patients than in controls (p = 4.15e-7). MS women presented higher MSRV load than control women (p = 0.009) and MS men also had higher load than control men (p = 2.77e-6). Besides, women had higher levels than men, both among patients (p = 0.007) and controls (p = 1.24e-6). Concordantly, EDSS and MSSS scores were higher among female patients with an elevated MSRV load (p = 0.03 and p = 0.04, respectively).ConclusionsMSRV increases its copy number in PBMC of MS patients and particularly in women with high clinical scores. This may explain causes underlying the higher prevalence of MS in women. The association with the clinical severity calls for further investigations on MSRV load in PBMCs as a biomarker for MS.

The aliens inside us: HERV-W endogenous retroviruses and multiple sclerosis

“…14 MSRV positivity increased in the relapses, 6 as well as with MS duration and progression, from onset up to secondary progressive MS (SPMS). 23,24,25,29,30 MSRV positivity of spinal fluids increased with MS duration, 23 and MS phase, 26 and its presence in early MS was related to worse prognosis in the next 10 years, as reported in a blind follow up of patients close to MS onset, starting in comparable conditions (but differing in MSRV positivity of the spinal fluids). The study showed that early MSRV presence in spinal fluids was associated with a significantly greater rate of disability and disease progression, detectable after 3, 31 6, 32 and 10 years.…”

Multiple sclerosis-associated retrovirus and related human endogenous retrovirus-W in patients with multiple sclerosis: A literature review

“…In contrast, Sotgiu et al (2006) reported in a 6-year follow-up study that patients with an initial MSRV + status showed significantly higher EDSS scores than patients who were MSRV − , even though pharmacologic intervention (chronic immunomodulatory or immunosuppressive treatment) was given to 90% of the MSRV + patients and to only 25% of the MSRV − patients, which does not suggest a reduction in MSRV positivity with intervention. Similarly, Garcia-Montojo et al (2013) reported higher EDSS scores among female patients with an elevated MSRV env load (copies/ pg of DNA) and with most patients (168/178) under treatment.…”

DNA methylation modulates HRES1/p28 expression in B cells from patients with Lupus

“…DNA methylation, the main epigenetic process, is abnormal in CD4 + T cells and B cells from SLE patients (Reviewed in [2]) leading to the overexpression of DNA methylation sensitive genes such as Human Endogenous Retroviruses (HERV). HERV detection is increased in patients with autoimmune diseases including SLE [3,4], Sjögren’s syndrome [5,6], and multiple sclerosis [7]. HERV are not only suspected to be markers of autoimmune diseases they are also suspected of contributing to the development of autoimmune diseases through different mechanisms.…”