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Cited by 90Multiple Sclerosis Research StudiesChromosomal and Genetic VariationsPolyomavirus and related diseases

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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

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Garcia-Montojo, Marta, Dominguez-Mozo, María, Arias-Leal, Ana, Garcia-Martinez, Ángel, De las Heras, Virginia, Casanova, Ignacio, Faucard, Raphaël, Gehin, Nadège, Madeira, Alexandra, Arroyo, Rafael, Curtin, François, Alvarez-Lafuente, Roberto, Perron, Hervé·2013·PLoS ONE
DOI 10.1371/journal.pone.0053623PMC PMC3538585
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Abstract

BACKGROUND: Multiple 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. RESULTS: 178 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). CONCLUSIONS: MSRV 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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Figure 1 MSRV DNA load MS diagnosis and sex. A) MSRV DNA load is more elevated in PBMC of MS patients (n = 178) than in controls (n = 124) (ANOVA; p = 4.15e-7). B) MSRV DNA load is more elevated in MS women (n = 112) than in control women (n = 70) (ANOVA; p = 0.009), control men (n = 54) (ANOVA; p = 8.87e-14) and MS men (n = 66) (ANOVA; p = 0.007). MSRV DNA load is more elevated in control women (n = 70) than in control men (n = 54) (ANOVA; p = 1.24e-6). Points represent the mean and bars represent 95% Confidence Interval of Mean. MSRV DNA load represents MSRV copies/pg of DNA.
Figure 1 MSRV DNA load MS diagnosis and sex. A) MSRV DNA load is more elevated in PBMC of MS patients (n = 178) than in controls (n = 124) (ANOVA; p = 4.15e-7). B) MSRV DNA load is more elevated in MS women (n = 112) than in control women (n = 70) (ANOVA; p = 0.009), control men (n = 54) (ANOVA; p = 8.87e-14) and MS men (n = 66) (ANOVA; p = 0.007). MSRV DNA load is more elevated in control women (n = 70) than in control men (n = 54) (ANOVA; p = 1.24e-6). Points represent the mean and bars represent 95% Confidence Interval of Mean. MSRV DNA load represents MSRV copies/pg of DNA.CC BY · PubMed Central
Figure 2 MSRV load and clinical evolution in women with MS. A) The EDSS Score is higher among patients with a MSRV DNA load above the Cut-Off* (Cut-Off = 2.22, corresponding to 165 copies/pg of DNA) (n = 7) than below (n = 101). ANOVA; p = 0.032. B) MSSS score is higher among patients with a MSRV DNA load above the Cut-Off*(n = 7) than below (n = 99). ANOVA; p = 0.044. Points represent the mean and bars represent 95% Confidence Interval of Mean. MSRV load represents MSRV copies/pg of DNA. *Cut-Off = Mean log10 MSRV DNA Controls +2*S.D log10 MSRV DNA Controls; This represents the threshold above which the values are no longer within the range of the normal population.
Figure 2 MSRV load and clinical evolution in women with MS. A) The EDSS Score is higher among patients with a MSRV DNA load above the Cut-Off* (Cut-Off = 2.22, corresponding to 165 copies/pg of DNA) (n = 7) than below (n = 101). ANOVA; p = 0.032. B) MSSS score is higher among patients with a MSRV DNA load above the Cut-Off*(n = 7) than below (n = 99). ANOVA; p = 0.044. Points represent the mean and bars represent 95% Confidence Interval of Mean. MSRV load represents MSRV copies/pg of DNA. *Cut-Off = Mean log10 MSRV DNA Controls +2*S.D log10 MSRV DNA Controls; This represents the threshold above which the values are no longer within the range of the normal population.CC BY · PubMed Central

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Metadata

Authors
Garcia-Montojo, M., Dominguez-Mozo, M., Arias-Leal, A., Garcia-Martinez, Á., De las Heras, V., Casanova, I., Faucard, R., Gehin, N., Madeira, A., Arroyo, R., Curtin, F., Alvarez-Lafuente, R., & Perron, H.
Affiliations
Hospital Clínico San Carlos (ES)
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2013-01-07
Volume
8
Issue
1
Pages
e53623
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0053623
PMC
PMC3538585
OpenAlex
W1977781262
Cited by
90
References
2
Citations by year
2026: 3 · 2025: 2 · 2024: 4 · 2023: 4 · 2022: 6 · 2021: 10 · 2020: 10 · 2019: 4 · 2018: 9 · 2017: 9 · 2016: 9 · 2015: 6 · 2014: 5 · 2013: 9
FWCI
7.25
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Funders
  • Instituto de Salud Carlos III
  • European Regional Development Fund
Topics
  • Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Chromosomal and Genetic Variations
  • Health Sciences › Medicine › Oncology › Polyomavirus and related diseases
Keywords
multiple sclerosis, MSRV, HERV-W, DNA copy number, sex differences, disease severity, peripheral blood mononuclear cells, biomarkers
MeSH terms
Adult, DNA, Viral, Female, Humans, Leukocytes, Mononuclear, Male, Middle Aged, Multiple Sclerosis, Severity of Illness Index, Sex Factors, Genes, env, Viral Load, Endogenous Retroviruses, Chromosomes, Human, X, DNA Copy Number Variations, Real-Time Polymerase Chain Reaction

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CoChat. (2026). Citation check: 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. https://app.cochat.ai/papers/10.1371/journal.pone.0053623
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Garcia-Montojo, M., Dominguez-Mozo, M., Arias-Leal, A., Garcia-Martinez, Á., De las Heras, V., Casanova, I., Faucard, R., Gehin, N., Madeira, A., Arroyo, R., Curtin, F., Alvarez-Lafuente, R., & Perron, H. (2013). 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. PLoS ONE. https://doi.org/10.1371/journal.pone.0053623