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 human endogenous retrovirus HERV-H is associated with multiple sclerosis (MS). Previously performed reverse transcriptase-polymerase chain reactio ns (RT-PC R) on virion-RNA demonstrated sequence variants of the HERV-H family located in the particulate fraction of MS patient plasma samples and not in controls. In this study a significantly elevated level of antibodies towards peptides derived from HERV-H/RGH-2 DNA sequences in serum and cerebrospinal fluid (C SF) from MS patients is demonstrated. Further, Wistar rats immunized with purified virions develop a specific serologic response, indicating that some virion proteins are encoded by HERV-H-related sequences. A lso shown is that in RNA from blood cells, a HERV-H protease-env splice variant can be found together with an env splice variant in about 40% of MS patients but only in 10% of controls. The results substantiate the association between activated HERV-H and MS, but a causal relationship is yet to be demonstrated. HERV-H could represent a causal factor either by eliciting an autoimmune response or through the pathogenic potential of the retrovirus itself.

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IL-2 and Mycobacterial Lipoarabinomannan as Targets of Immune Responses in Multiple Sclerosis Patients

Microorganisms ◽

10.3390/microorganisms8040500 ◽

2020 ◽

Vol 8 (4) ◽

pp. 500 ◽

Cited By ~ 2

Author(s):

Marco Bo ◽

Magdalena Niegowska ◽

Jessica Frau ◽

GianPietro Sechi ◽

Giannina Arru ◽

...

Keyword(s):

Multiple Sclerosis ◽

Mycobacterium Avium Subspecies Paratuberculosis ◽

Interleukin 2 ◽

Endogenous Retrovirus ◽

Human Endogenous Retrovirus ◽

Slight Reduction ◽

Multiple Sclerosis Patients ◽

The Impact ◽

Ms Pathogenesis ◽

Future Practice

Interleukin 2 (IL-2) is considered a key player in exacerbating multiple sclerosis (MS). Therapies targeting its receptor have been developed; however, a resolution of the disease and side effects are still an issue of concern. The involvement of other factors, such as Mycobacterium avium subspecies paratuberculosis (MAP) and envelope protein derived from human endogenous retrovirus type W (HERV-Wenv), in MS pathogenesis has been recently suggested. Here, we investigated the levels of antibodies (Abs) directed against IL-2 and HERV-Wenv in 108 MS patients, 34 patients affected by neuromyelitis optica spectrum disorder (NMOSD), and 137 healthy controls (HCs). Our results show increased levels of Abs specific to IL-2 and HERV-Wenv-su antigens in MS vs. HCs (p < 0.0001 for IL-2, p = 0.0004 for HERV-Wenv) and significantly decreased levels in NMOSD vs. MS. The assessment of different 12-month-long therapies on Abs against IL-2, HERV-Wenv, and MAP lipoarabinomannan (LAM) demonstrated the strongest effect on anti-LAM Abs (p = 0.018), a slight reduction of anti-IL-2 Abs, and small variations for anti-HERV-Wenv Abs. These results highlight the conclusion that the impact of therapy is more correlated with selected epitopes than with the therapeutic agent. Screening for anti-IL-2 and anti-HERV-Wenv Abs has a potential as additional future practice to distinguish between symptomatically similar MS and NMOSD.

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THE COMPARATIVE STUDY OF HUMAN ENDOGENOUS RETROVIRUS HERV-E λ 4-1 EXPRESSION IN BLOOD IMMUNE CELLS OF MULTIPLE SCLEROSIS PATIENTS

Medical academic journal ◽

10.17816/maj191s178-80 ◽

2019 ◽

Vol 19 (1S) ◽

pp. 78-80

Author(s):

I A Goldina ◽

E V Markova

Keyword(s):

Multiple Sclerosis ◽

Immune Cells ◽

Mononuclear Cells ◽

Mrna Level ◽

Endogenous Retrovirus ◽

Pokeweed Mitogen ◽

Human Endogenous Retrovirus ◽

Peripheral Blood Mononuclear ◽

Blood Mononuclear Cells ◽

Multiple Sclerosis Patients

In order to investigate the function of human endogenous retrovirus HERV-E λ 4-1 in multiple sclerosis pathogenesis, the comparative research of frequency of this retrovirus expression and mRNA level on different types of blood immune cells of progredient course multiple sclerosis patients have been conducted with using of the reverse - transcriptase polymerase chain reaction method. Peripheral blood mononuclear cells were isolated on Ficoll density gradient centrifugations. Monocytes were separated by the adhesion to plastic Petri dishes. For the estimation of the mitogen-induced HERV-E λ 4-1 expression, blood mononuclear cells were incubated with adding of phytogemagglutinin or pokeweed mitogen during 72 hours in CO2 incubator at 37 °C and 5% CO2. Results of HERV-E λ 4-1 env gene expression estimation demonstrate that both monocytes and lymphocytes express HERV-E λ 4-1. The level of the HERV-E λ 4-1 env mRNA was higher in lymphocytes than in monocytes. The main source of HERV-E λ 4-1 in progredient course MS patients between blood immune cells are lymphocytes, especially B lymphocytes.

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INVESTIGATION OF BLOOD MONONUCLEAR CELLS CYTOKINE-PRODUCTION FUNCTION FROM PATIENTS WITH MULTIPLE SCLEROSIS TREATED WITH THE ENDOGENOUS RETROVIRUS HERV-E λ 4-1 CONSERVATIVE REGION SYNTHETIC OLIGOPEPTIDE

Medical Immunology (Russia) ◽

10.15789/1563-0625-iob-2241 ◽

2021 ◽

Vol 23 (4) ◽

pp. 749-754

Author(s):

I. A. Goldina ◽

E. V. Markova

Keyword(s):

Multiple Sclerosis ◽

Mononuclear Cells ◽

Culture Supernatant ◽

Transmembrane Protein ◽

Endogenous Retrovirus ◽

Human Endogenous Retrovirus ◽

Healthy Individuals ◽

Spontaneous Production ◽

Blood Mononuclear Cells ◽

Multiple Sclerosis Patients

Considering to the data of class I human endogenous retrovirus HERV-Е λ 4-1 subgroup association with multiple sclerosis, an autoimmune disease accompanied by neuroinflammation, changes in the neurotransmitters level, progressive neurological dysfunction, as well as the ability of this retrovirus to replicate and to produce proteins with potential immunomodulatory properties, the aim of this work was a comparative study of the blood immune cells cytokine synthesizing function in conventionally healthy individuals and multiple sclerosis patients under the synthetic 17 – amino acid oligopeptide homologous to the hydrophobic transmembrane protein р15Е HERV-Е λ 4-1 conserved region influence. The 40 patients, 17 male persons aged 38.0 (31.0-47.0) years old and 23 female persons aged 39.0 (31.0-50.0) years old with an established diagnosis of multiple sclerosis (G 35, ICD-10), corresponding to the McDonald 2005, modified in 2010 criteria with a continuously progressive disease course and the disease duration of 17.0 (14.0-18.0) years, and 30 conditionally healthy individuals, 12 male persons aged 32.0 (23.0-43.0) years old and 18 female persons aged 36.0 (29.0-46.0) years old were the objects of the study. An open-label, observational, single-center, cohort, controlled, randomized trial was conducted. It was found that the donor’s blood mononuclear cells IL-1β, IL-6, TNFα, IFNγ and IL-2 spontaneous production in culture was stimulated, but that of IL-4 and IL-10 did not change under the retroviral oligopeptide influence. At the same time, the spontaneous and mitogenstimulated production of all studied cytokines did not change under the control oligopeptide influence. The PHA-stimulated donor’s blood mononuclear cells cultivation in presence of the retroviral oligopeptide, as compared to the control one, was accompanied by an increase in the IL-1β, IL-6 and TNFα release into the culture supernatant. The multiple sclerosis patients were characterized by IL-1β, IL-6 and IFNγ higher content in the mitogen-unstimulated blood mononuclear cells culture supernatant, compared with conditionally healthy individuals, as well as by a higher production of IL-6 and IFNγ in response to PHA stimulation. The retroviral oligopeptide, in contrast to the control one, stimulated the IL-1β, IL-6, TNFα and IFNγ spontaneous production without altering that of IL-4 and IL-10 in multiple sclerosis patients. The obtained results indicate that the synthetic oligopeptide homologous to the conserved region of the hydrophobic transmembrane protein p15E HERV-Е λ 4-1 has the pro-inflammatory properties, which is probably the one of human endogenous retrovirus HERV-Е λ 4-1 pathological abilities realization mechanism in multiple sclerosis.

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