Leptomeningeal cell line from multiple sclerosis with reverse transcriptase activity and viral particles

Perron, Hervé; Gény, Christian; Laurent, Angela M.; Mouriquand, C; Pellat, J; Perret, Jean‐Luc; Seigneurin, J. M.

doi:10.1016/s0923-2516(89)80141-4

Cited by 145 publications

(96 citation statements)

References 11 publications

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“…Because MSRV was first isolated in choroid plexus/leptomeningeal cell cultures from multiple sclerosis patients (12,13), and virion-associated MSRV RNA can be detected in sera and/or cerebrospinal fluids of such patients (39,40), it is plausible that its envelope protein can exert its CD14/TLR4-dependent proinflammatory effect within the CNS, and therefore initiates and/or substantially exacerbates the disorder. This idea is in line with the findings that: 1) HERV-W ENV and GAG glycoproteins are expressed in the white matter of patients with multiple sclerosis (41)(42)(43), and that 2) the virus load detected in the CSF increases with MS progression and thus may have prognosis value (38).…”

Section: Discussionmentioning

confidence: 99%

“…Multiple sclerosis-associated retroviral element (MSRV) is an enveloped virus with reverse-transcriptase activity (10) that represents the prototype genome that defined the HERV-W family in human DNA (3,11) and was initially isolated in cell cultures from patients affected by the severe inflammatory demyelinating disorder of the CNS multiple sclerosis (12,13). The origin of MSRV particles is still unclear.…”

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confidence: 99%

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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

238

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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Section: Discussionmentioning

confidence: 99%

mentioning

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

238

254

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“…Various studies suggest that, in eliciting MS, there occur intricate interactions between genetic factors and various other factors, including infectious agents ( Figure 1) [28,29]. The connection between genetic and infectious components is exemplified by the human endogenous retroviruses (HERV) [30,31]. Viral infections sometimes trigger exacerbations of MS and can lead to direct damage of oligodendroglia and T cells [32].…”

Section: Introductionmentioning

confidence: 99%

Human Immunodeficiency Virus and Multiple Sclerosis Risk: Probing for a Connection

Khan

Zahoor²,

Haq³

2015

J Mult Scler

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Multiple Sclerosis (MS) is a chronic autoimmune inflammatory disease of the nervous system, with intense genetic and environmental background. Its etiology is poorly understood and likely multifactorial but its epidemiology has been intensively studied. This complex disease displays heterogeneity in terms of geographic and genetic influences on incidence, insinuating an effect of local unknown environmental factors on its development. Among numerous potential factors putatively involved in the etiopathogenesis of MS, retroviruses appear to influence MS. The intent of this review is to highlight the association between human immunodeficiency virus (HIV) and the risk of developing MS while at the same time providing an overview of the insights gleaned from different studies. HIV infection is associated with a reduced risk of MS development, and perhaps, appears to be another wedge of the MS conundrum. The probable mechanisms for this relationship may be suppression of the immune system and/or antiretroviral drug therapy. While highlighting the relevance of antiretroviral medications as potential future alternatives for the effective treatment of MS, this review provides an impetus for further studies. We conclude that studies in this milieu hitherto are insufficient, and there is need for an upsurge in molecular epidemiological and clinical studies, with focus on the mechanism behind the impact of HIV/antiretroviral drugs on MS. Such inquiry could precisely establish the causes for associations between HIV and MS, perhaps impacting treatment options for both.

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“…They are structurally similar to retroviral mRNA, followed by a poly(A) tail. These elements are frequently observed in the HERV-W family (Blond et al 1999), described previously as LM7 or multiple sclerosis-associated virus (Perron et al 1989, and as endogenous HERV17 family in the Repbase Update database (http://www.girinst.org/; Jurka 1998Jurka , 2000Smit 1999). The HERV-W family is of special interest because of suggestions of a role in several human diseases including multiple sclerosis Komurian-Pradel et al 1999), rheumatoid arthritis (Gaudin et al 1997(Gaudin et al , 2000, and schizophrenia (Karlsson et al 2001).…”

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confidence: 99%

Processed Pseudogenes of Human Endogenous Retroviruses Generated by LINEs: Their Integration, Stability, and Distribution

Pavlı́ček¹,

Pačes²,

Elleder³

et al. 2002

Genome Res.

117

109

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We report here the presence of numerous processed pseudogenes derived from the W family of endogenous retroviruses in the human genome. These pseudogenes are structurally colinear with the retroviral mRNA followed by a poly(A) tail. Our analysis of insertion sites of HERV-W processed pseudogenes shows a strong preference for the insertion motif of long interspersed nuclear element (LINE) retrotransposons. The genomic distribution, stability during evolution, and frequent truncations at the 5Ј end resemble those of the pseudogenes generated by LINEs. We therefore suggest that HERV-W processed pseudogenes arose by multiple and independent LINE-mediated retrotransposition of retroviral mRNA. These data document that the majority of HERV-W copies are actually nontranscribed promoterless pseudogenes. The current search for HERV-Ws associated with several human diseases should concentrate on a small subset of transcriptionally competent elements.

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Leptomeningeal cell line from multiple sclerosis with reverse transcriptase activity and viral particles

Cited by 145 publications

References 11 publications

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

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

Human Immunodeficiency Virus and Multiple Sclerosis Risk: Probing for a Connection

Processed Pseudogenes of Human Endogenous Retroviruses Generated by LINEs: Their Integration, Stability, and Distribution

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