Multiple Sclerosis-Associated Virus-Related pol Sequences Found Both in Multiple Sclerosis and Healthy Donors are More Frequently Expressed in Multiple Sclerosis Patients

Nowak, Jerzy; Januszkiewicz, Danuta; Pernak, Monika; Liweń, Izabela; Zawada, M; Rembowska, Jolanta; Nowicka, Karina; Lewandowski, Krzysztof; Hertmanowska, H; Wender, M

doi:10.1080/13550280390173355

Cited by 46 publications

(24 citation statements)

References 23 publications

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“…Several groups have shown increased levels of MSRV-type or total HERV-W RNA transcription in serum, brain or PBMCs of MS patients compared to controls [17], [40], [41]. The reverse-transcription and eventual retrotransposition of mRNA would favor an increase in its genomic copy number, thus detected among the whole PBMCs genomic DNA from present samples (comprising altogether Monocytes, NK cells, T- and B-Lymphocytes).…”

Section: Resultsmentioning

confidence: 77%

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

et al. 2013

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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.

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Section: Resultsmentioning

confidence: 77%

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

et al. 2013

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“…Despite the diversity of findings related to HERV expression, with several conflicting and negative reports (40), numerous studies in the past have reported expression of HERVs in MS (13,17,49). This applies to particles, viral proteins, and viral RNA (22,37,45). However, causality has been notoriously difficult to establish from these experiments.…”

Section: Discussionmentioning

confidence: 87%

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

Laska

Brudek

Nissen

et al. 2012

J Virol

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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.

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“…Perhaps it should be noted at this point, that even though pol sequences are considered the most conserved among the retroviral genes, the broad range pol primers used in HERV-W amplifications correspond to regions 190 190 T. Christensen T. Christensen that are variant in many HERV-H pol sequences, and thus these primers are inefficient in HERV-H amplification [162]. A Polish study also reported MSRV pol sequences in all MS sera and a large proportion of controls [163]. Finally, in a Swedish study also assaying for MSRV/HERV-W pol sequences, the authors found that serum from one of nine samples from MS patients was positive (a pregnant woman), whereas all controls were negative [164].…”

Section: Rt-pcr and Characterisation Of Herv Sequencesmentioning

confidence: 96%

Association of human endogenous retroviruses with multiple sclerosis and possible interactions with herpes viruses

2005

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The hypothesis that human endogenous retroviruses (HERVs) play a role in autoimmune diseases is subject to increasing attention. HERVs represent both putative susceptibility genes and putative pathogenic viruses in the immune-mediated neurological disease multiple sclerosis (MS). Gammaretroviral HERV sequences are found in reverse transcriptase-positive virions produced by cultured mononuclear cells from MS patients, and they have been isolated from MS samples of plasma, serum and CSF, and characterised to some extent at the nucleotide, protein/enzyme, virion and immunogenic level. Two types of sequences, HERV-H and HERV-W, have been reported. No known HERV-H or HERV-W copy contains complete ORFs in all prerequisite genes, although several copies have coding potential, and several such sequences are specifically activated in MS, apparently resulting in the production of complete, competent virions. Increased antibody reactivity to specific Gammaretroviral HERV epitopes is found in MS serum and CSF, and cell-mediated immune responses have also been reported. Further, HERV-encoded proteins can have neuropathogenic effects. The activating factor(s) in the process resulting in protein or virion production may be members of the Herpesviridae. Several herpes viruses, such as HSV-1, VZV, EBV and HHV-6, have been associated with MS pathogenesis, and retroviruses and herpes viruses have complex interactions. The current understanding of HERVs, and specifically the investigations of HERV activation and expression in MS are the major subjects of this review, which also proposes to synergise the herpes and HERV findings, and presents several possible pathogenic mechanisms for HERVs in MS.

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Multiple Sclerosis-Associated Virus-Related pol Sequences Found Both in Multiple Sclerosis and Healthy Donors are More Frequently Expressed in Multiple Sclerosis Patients

Cited by 46 publications

References 23 publications

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

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

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

Association of human endogenous retroviruses with multiple sclerosis and possible interactions with herpes viruses

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