In vitro transmission and antigenicity of a retrovirus isolated from a multiple sclerosis patient

Perron, Hervé; Gratacap, B.; Lalande, B.; Genoulaz, O.; Laurent, Angela M.; Gény, Christian; Mallaret, Martial; Innocenti, P; Schuller, E; Stoebner, P; Seignerurin, J.M.

doi:10.1016/s0923-2516(06)80122-6

Cited by 36 publications

(24 citation statements)

References 23 publications

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“…Apart from ERV9, the closest known retroviral element is RTLV-H, a human endogenous sequence known to have a subtype with a functional pol gene (22). In the pol region, this phylogenic affiliation to C-type oncoviruses apparently contradicts our previous assumptions based on the general morphology of the particles observed by electron microscopy, which were compatible with a B-or D-type oncovirus (9,11). However, preliminary data on env sequences detected in MSRV virions suggest a greater phylogenic proximity to D-type.…”

Section: Phylogeny Of Msrvcontrasting

confidence: 82%

“…Neither viral particles nor viral RT activity was found in control individuals. Furthermore, we were able to transfer the LM7 virus to noninfected leptomeningeal cells in vitro (11). The molecular characterization of the ''LM7'' retrovirus was a prerequisite for further evaluation of its possible role in MS.…”

mentioning

confidence: 99%

“…RT activity was tested as described (9)(10)(11)(12). cDNA Synthesis and ''Pan-Retro'' RT-PCR with Degenerate Primers.…”

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confidence: 99%

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Molecular identification of a novel retrovirus repeatedly isolated from patients with multiple sclerosis

Perron

Garson²,

Bedin³

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

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430

311

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The partial molecular characterization of multiple sclerosis (MS)-associated retrovirus (MSRV), a novel retrovirus previously called LM7, is reported. MSRV has been isolated repeatedly from leptomeningeal, choroid plexus and from Epstein-Barr virus-immortalized B cells of MS patients. A strategy based on reverse transcriptase PCR with RNA-purified extracellular virions yielded an initial pol fragment from which other regions of the retroviral genome were subsequently obtained by sequence extension. MSRVspecific PCR primers amplified a pol region from RNA present at the peak of reverse transcriptase activity, coinciding with extracellular viral particles in sucrose density gradients. The same sequence was detected in noncellular RNA from MS patient plasma and in cerebrospinal f luid from untreated MS patients. MSRV is related to, but distinct from, the endogenous retroviral sequence ERV9. Whether MSRV represents an exogenous retrovirus with closely related endogenous elements or a replication-competent, virion-producing, endogenous provirus is as yet unknown. Further molecular epidemiological studies are required to determine precisely the apparent association of virions containing MSRV RNA with MS.

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Section: Phylogeny Of Msrvcontrasting

confidence: 82%

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confidence: 99%

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Molecular identification of a novel retrovirus repeatedly isolated from patients with multiple sclerosis

Perron

Garson²,

Bedin³

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

430

311

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“…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%

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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“…The origin of MSRV particles is still unclear. They could originate from a modified endogenous HERV-W provirus or from a transmissible exogenous member of the same family (11,14,15). It was observed previously that MSRV virions trigger the secretion of IL-6 and TNF-␣ proinflammatory cytokines by human PBMC in culture (16).…”

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confidence: 99%

The Envelope Protein of a Human Endogenous Retrovirus-W Family Activates Innate Immunity through CD14/TLR4 and Promotes Th1-Like Responses

Rolland

Jouvin‐Marche

Viret

et al. 2006

The Journal of Immunology

246

254

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Multiple sclerosis-associated retroviral element (MSRV) is a retroviral element, the sequence of which served to define the W family of human endogenous retroviruses. MSRV viral particles display proinflammatory activities both in vitro in human mononuclear cell cultures and in vivo in a humanized SCID mice model. To understand the molecular basis of such properties, we have investigated the inflammatory potential of the surface unit of the MSRV envelope protein (ENV-SU), the fraction that is poised to naturally interact with host cells. We report in this study that MSRV ENV-SU induces, in a specific manner, human monocytes to produce major proinflammatory cytokines through engagement of CD14 and TLR4, which are pattern recognition receptors of primary importance in innate immunity. ENV-SU could also trigger a maturation process in human dendritic cells. Finally, ENV-SU endowed dendritic cells with the capacity to support a Th1-like type of Th cell differentiation. The data are discussed in the context of immune responses and chronic proinflammatory disorders.

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In vitro transmission and antigenicity of a retrovirus isolated from a multiple sclerosis patient

Cited by 36 publications

References 23 publications

Molecular identification of a novel retrovirus repeatedly isolated from patients with multiple sclerosis

Molecular identification of a novel retrovirus repeatedly isolated from patients with multiple sclerosis

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

The Envelope Protein of a Human Endogenous Retrovirus-W Family Activates Innate Immunity through CD14/TLR4 and Promotes Th1-Like Responses

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