Cell cultures and associated retroviruses in multiple sclerosis

Perron, Hervé; Firouzi, Réza; Tuke, Philip W.; Garson, Jeremy A.; Michel, M.; Beseme, F.; Bedin, F.; Mallet, François; Marcel, Enrique Abraham; Seigneurin, J. M.; Mandrand, Bernard

doi:10.1111/j.1600-0404.1997.tb08146.x

Cited by 35 publications

(36 citation statements)

References 12 publications

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“…A similar observation was obtained in larger series of patients when we adapted blood monocyte culture to the detection of this retroviral activity [13]. We later confirmed the association of a specific retroviral RNA with these extracellular virions, and the apparent association between MS activity and their release in MMCS [17,14]. We also observed retroviral-like particles produced by MS MMC in phase with a burst of RT activity [13].…”

Section: Discussionsupporting

confidence: 68%

“…The MSRV polymerase RNA sequence encoding the protease and the RT is compatible with that of an exogenous retrovirus sharing extensive homology with a family of human endogenous retroviruses or with that of a replication-competent endogenous retrovirus [16]. Cultured blood monocytes from MS patients with active disease were found to express low but significant RT activity in the cell culture supernatants [13,17]. Macrophage cells are quite active in MS lesions as previously mentioned, as well as in visna, a natural animal model of MS [18][19][20].…”

mentioning

confidence: 93%

“…activity Since a significant gliotoxicity associated with cultures from MS patients was observed, it was decided to analyze for any correlation between this cytotoxicity and the RT activity previously reported in MMCS from 'active' MS patients [13,17,30]. The results are presented for both the gliotoxic activity measured by the MTT assay on CLTT 1-1 cells (Fig.…”

Section: Correlation Of Cytotoxic Activity and Reverse Transcriptasementioning

confidence: 99%

“…The MMCS, harvested and completely renewed every three days, were pooled for the periods between days 3 to 6 and 9 to 15. The supernatants from day 1, which preceded macrophage differentiation, was tested separately [17]. Significant gliotoxicity (Fig.…”

Section: Correlation Of Cytotoxic Activity and Reverse Transcriptasementioning

confidence: 99%

“…O. Lyon-Caen). All the MS patients were diagnosed according to the standard criteria of Poser et al [23,24,8], All blood samples and monocyte/macrophage cultures were processed as previously described [17].…”

Section: Monocyte/macrophage Blood Cellsmentioning

confidence: 99%

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Gliotoxicity, reverse transcriptase activity and retroviral RNA in monocyte/macrophage culture supernatants from patients with multiple sclerosis

et al. 1997

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In investigating a possible link between a novel retroviral agent (provisionally called MSRV), recently characterised in multiple sclerosis (MS), and the neuropathology of MS, it was found that there was a significant correlation between gliotoxicity and reverse transcriptase activity in monocyte/ macrophage culture supernatants (MMCS) unique to MS patients. MMCS from healthy controls and patients with other neurological diseases did not display either gliotoxicity or reverse transcriptase activity. The observed gliotoxic effect was an initial, intermediate filament network disorganization and subsequent cell death which was specific to astrocytes and oligodendrocytes. The reverse transcriptase activity and MSRVspecific RNA were observed during the first 2 weeks of culture in MMCS from patients with active MS. The further elucidation of the molecular form(s) of this gliotoxic factor and its original source may be crucial in elucidating important etiopathogenic mechanisms in MS.

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Section: Discussionsupporting

confidence: 68%

mentioning

confidence: 93%

Section: Correlation Of Cytotoxic Activity and Reverse Transcriptasementioning

confidence: 99%

Section: Correlation Of Cytotoxic Activity and Reverse Transcriptasementioning

confidence: 99%

Section: Monocyte/macrophage Blood Cellsmentioning

confidence: 99%

See 3 more Smart Citations

Gliotoxicity, reverse transcriptase activity and retroviral RNA in monocyte/macrophage culture supernatants from patients with multiple sclerosis

et al. 1997

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mAbs Targeting Apoptosis, Angiogenesis Inhibitors, and Other mAbs in Phase 1 and 2 Clinical Studies for Immunological Disorders

Brennan

2014

Handbook of Therapeutic Antibodies

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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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Cell cultures and associated retroviruses in multiple sclerosis

Cited by 35 publications

References 12 publications

Gliotoxicity, reverse transcriptase activity and retroviral RNA in monocyte/macrophage culture supernatants from patients with multiple sclerosis

Gliotoxicity, reverse transcriptase activity and retroviral RNA in monocyte/macrophage culture supernatants from patients with multiple sclerosis

mAbs Targeting Apoptosis, Angiogenesis Inhibitors, and Other mAbs in Phase 1 and 2 Clinical Studies for Immunological Disorders

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

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