Detection of a gliotoxic activity in the cerebrospinal fluid from multiple sclerosis patients

Ménard, Armelle; Pierig, Régine; Pelletier, Jean; Bensa, P.; Belliveau, James F.; Mandrand, Bernard; Perron, Hervé; Rieger, François

doi:10.1016/s0304-3940(98)00171-2

Cited by 16 publications

(11 citation statements)

References 8 publications

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“…A CSF-mediated factor perhaps offers a more straightforward explanation, being in close proximity to both the inner and outer brain surfaces. However, while there is in vitro evidence that CSF from people with MS is both myelotoxic and neurotoxic,27 28 this has not been shown in vivo . Meningeal inflammation has been implicated in the pathogenesis of cortical GM lesions, and lesional and extralesional neuronal loss,11 12 but ependymal changes in MS do not appear to be closely linked with underlying WM lesion formation1 and, to the best of our knowledge, no studies have looked for associations between ependymal abnormalities and axonal pathology in WM.…”

Section: Discussionmentioning

confidence: 97%

Relationship of grey and white matter abnormalities with distance from the surface of the brain in multiple sclerosis

Pardini

Sudre

Prados

et al. 2016

J Neurol Neurosurg Psychiatry

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Section: Discussionmentioning

confidence: 97%

Relationship of grey and white matter abnormalities with distance from the surface of the brain in multiple sclerosis

Pardini

Sudre

Prados

et al. 2016

J Neurol Neurosurg Psychiatry

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“…Production of pathogenic (inflammatory or death signaling) molecules has been associated with retroviral expression [130], especially the envelope protein [2]. It has been postulated that there may exist a pathogenic cascade in MS involving several step-specific pathogens interacting with particular genetic elements leading to enhanced retroviral expression [200].…”

Section: Discussionmentioning

confidence: 99%

“…The pol and env genes of MSRV and their expressed proteins have also been shown to be involved in inflammatory responses [129]. Gliotoxins secreted from macrophages expressing MSRV also caused the death of oligodendrocytes, key cells involved in the myelination process [130]. This finding might suggest a direct inflammatory role for MSRV gene products.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

“…MSRV can be transactivated in vitro by two Herpes Simplex Virus type 1 immediate early proteins [202] [202] and thus act as triggering cofactors of MSRV in the pathogenesis of MS. In a similar fashion, MS long term lymphocyte cell lines, which are EBV transformed B cells with a T cell sub-population, with high reverse transcriptase activity attributed to HERV-H RVLP, also produced significant levels of IL-2, IFN-, GM-CSF and TNF- [107].However, MSRV showed a different cytokine profile with patient lymphocytes and with no correlation to RT activity[130]. In fact, cytokines such as IL-4, IL-6, TNF- and IFN- might induce the release of MSRV particles thereby contributing to the pathogenic feedback loop[125].…”

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confidence: 99%

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Human endogenous retroviruses and multiple sclerosis: Innocent bystanders or disease determinants?

Antony

Deslauriers

Bhat

et al. 2011

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

109

127

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Human endogenous retroviruses (HERVs) constitute 5-8% of human genomic DNA and are replication incompetent despite expression of individual HERV genes from different chromosomal loci depending on the specific tissue. Several HERV genes have been detected as transcripts and proteins in the central nervous system, frequently in the context of neuroinflammation. The HERV-W family has received substantial attention in large part because of associations with diverse syndromes including multiple sclerosis (MS) and several psychiatric disorders. A HERV-W-related retroelement, multiple sclerosis retrovirus (MSRV), has been reported in MS patients to be both a biomarker as well as an effector of aberrant immune responses. HERV-H and HERV-K have also been implicated in MS and other neurological diseases but await delineation of their contributions to disease. The HERV-W envelope-encoded glycosylated protein, syncytin-1, is encoded by chromosome 7q21 and exhibits increased glial expression within MS lesions. Overexpression of syncytin-1 in glia induces endoplasmic reticulum stress leading to neuroinflammation and the induction of free radicals, which damage proximate cells. Syncytin-1's receptor, ASCT1 is a neutral amino acid transporter expressed on glia and is suppressed in white matter of MS patients. Of interest, antioxidants ameliorate syncytin-1's neuropathogenic effects raising the possibility of using these agents as therapeutics for neuroinflammatory diseases. Given the multiple insertion sites of HERV genes as complete and incomplete open reading frames, together with their differing capacity to be expressed and the complexities of individual HERVs as both disease markers and bioactive effectors, HERV biology is a compelling area for understanding neuropathogenic mechanisms and developing new therapeutic strategies.

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“…It forms extracellular virus particles in cultured B-cells and specific RNA has been amplified from CSF and peripheral blood cells in MS patients but not in controls including cases of encephalitis and myelitis. Recently, an expression of a cytotoxic factor specific for glial cells including oligodendrocytes has been detected in supernatants of MSRV-containing peripheral blood cells, as well as in CSF drawn from MS patients (Menard et al, 1998).…”

Section: A Retroviral Connectionmentioning

confidence: 99%

Herpesviruses—a rationale for antiviral treatment in multiple sclerosis

Bergström

1999

Antiviral Research

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In multiple sclerosis (MS), the extensive and long lasting search for viruses or other pathogens has hitherto failed to identify a common etiological agent. However, the beneficial effects by interferon-beta treatment in MS, although suggested to depend mainly on immunomodulation, might lend support to a viral involvement in the pathogenesis. The human herpesviruses have attracted interest since their recurrent modes of infection share some similarity with the relapsing-remitting course of MS, most members are readily detected within the brain, and several of these viruses may induce demyelination within the central nervous system in human hosts as well as in animal models. Accumulated diagnostic and epidemiological data are compatible with a role for the herpesviruses as possible cofactors rather than etiological agents, and recent studies showing early neuronal damage in MS patients focus attention on the neurotropic alpha-herpesviruses. Antiviral treatment trials with safe and effective drugs such as valaciclovir offer a possibility of testing the hypotheses concerning herpesviral involvement in MS.

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Detection of a gliotoxic activity in the cerebrospinal fluid from multiple sclerosis patients

Cited by 16 publications

References 8 publications

Relationship of grey and white matter abnormalities with distance from the surface of the brain in multiple sclerosis

Relationship of grey and white matter abnormalities with distance from the surface of the brain in multiple sclerosis

Human endogenous retroviruses and multiple sclerosis: Innocent bystanders or disease determinants?

Herpesviruses—a rationale for antiviral treatment in multiple sclerosis

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