Correlation between disease severity and in vitro cytokine production mediated by MSRV (Multiple Sclerosis associated RetroViral element) envelope protein in patients with multiple sclerosis

Rolland, Alexandre; Jouvin‐Marche, Evelyne; Saresella, Marina; Ferrante, Pasquale; Cavaretta, Rosella; Créange, Alain; Marche, Patrice N.; Perron, Hervé

doi:10.1016/j.jneuroim.2004.10.019

Cited by 71 publications

(65 citation statements)

References 30 publications

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“…Functional HERV Env proteins have been postulated to cause neuropathogenic effects (2,35,40). Among the HML-2 family members, six proviruses with a coding env gene were identified (7).…”

Section: Discussionmentioning

confidence: 99%

Human Endogenous Retrovirus Expression Profiles in Samples from Brains of Patients with Schizophrenia and Bipolar Disorders

Frank

Giehl

Zheng

et al. 2005

J Virol

150

163

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The detection and identification of retroviral transcripts in brain samples, cerebrospinal fluid, and plasma of individuals with recent-onset schizophrenia and schizoaffective disorders suggest that activation or upregulation of distinct human endogenous retroviruses (HERVs) may play a role in the etiopathogenesis of neuropsychiatric diseases. To test this hypothesis, we performed a comprehensive microarray-based analysis of HERV transcriptional activity in human brains. We investigated 50 representative members of 20 HERV families in a total of 215 brain samples derived from individuals with schizophrenia or bipolar disorders and matched controls. A characteristic brain-specific retroviral activity profile was found that consists of members of the class I families HERV-E, HERV-F, and ERV9 and members of HERV-K taxa. In addition to these constitutively expressed HERVs, a number of differentially active HERV elements were identified in all brain samples independent of the disease pattern that may reflect differences in the genetic background of the tested individuals. Only a subgroup of the HML-2 family (HERV-K10) was significantly overrepresented in both bipolar-disorder-and schizophrenia-associated samples compared to healthy brains, suggesting a potential association with disease. Real-time PCR analysis of HERV env transcripts with coding capacity potentially involved in neuroinflammatory conditions revealed that env expression of HERV-W, HERV-FRD, and HML-2 remains unaffected regardless of the clinical picture. Our data suggest that HERV transcription in brains is weakly correlated with schizophrenia and related diseases but may be influenced by the individual genetic background, brain-infiltrating immune cells, or medical treatment.

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“…Functional HERV Env proteins have been postulated to cause neuropathogenic effects (2,35,40). Among the HML-2 family members, six proviruses with a coding env gene were identified (7).…”

Section: Discussionmentioning

confidence: 99%

Human Endogenous Retrovirus Expression Profiles in Samples from Brains of Patients with Schizophrenia and Bipolar Disorders

Frank

Giehl

Zheng

et al. 2005

J Virol

150

163

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“…Mock-induced cytokines remained below the detection threshold. Finally, separate experiments have revealed that secretion of IFN-␥ and IL-10 is marginal in PBMC cultures treated for 24 h with soluble ENV-SU (20). Thus, ENV-SU induces the secretion of major proinflammatory cytokines in human PBMC cultures from healthy donors.…”

Section: Env-su Stimulates the Production Of Proinflammatory Cytokinementioning

confidence: 96%

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

Self Cite

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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“…This paper therefore provides a direct link between MSRV/HERV-W and the immunopathological events in MS. Consistent with those findings, in vitro stimulation of peripheral blood mononuclear cells (PBMCs) by the HERV-W Env protein induces the production of IL-12-p40, IL-6, and IFN-␥, with divergent reactivities between cells from MS patients and those from controls (419). These cytokines are proposed to be elicited by the stimulation of monocytes by MSRV/HERV-W Env acting through Tolllike receptor 4 (420).…”

Section: Retroviruses Associated With Multiple Sclerosismentioning

confidence: 68%

Human RNA “Rumor” Viruses: the Search for Novel Human Retroviruses in Chronic Disease

Voisset

Weiss

Griffiths

2008

Microbiol Mol Biol Rev

143

156

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SUMMARY Retroviruses are an important group of pathogens that cause a variety of diseases in humans and animals. Four human retroviruses are currently known, including human immunodeficiency virus type 1, which causes AIDS, and human T-lymphotropic virus type 1, which causes cancer and inflammatory disease. For many years, there have been sporadic reports of additional human retroviral infections, particularly in cancer and other chronic diseases. Unfortunately, many of these putative viruses remain unproven and controversial, and some retrovirologists have dismissed them as merely “human rumor viruses.” Work in this field was last reviewed in depth in 1984, and since then, the molecular techniques available for identifying and characterizing retroviruses have improved enormously in sensitivity. The advent of PCR in particular has dramatically enhanced our ability to detect novel viral sequences in human tissues. However, DNA amplification techniques have also increased the potential for false-positive detection due to contamination. In addition, the presence of many families of human endogenous retroviruses (HERVs) within our DNA can obstruct attempts to identify and validate novel human retroviruses. Here, we aim to bring together the data on “novel” retroviral infections in humans by critically examining the evidence for those putative viruses that have been linked with disease and the likelihood that they represent genuine human infections. We provide a background to the field and a discussion of potential confounding factors along with some technical guidelines. In addition, some of the difficulties associated with obtaining formal proof of causation for common or ubiquitous agents such as HERVs are discussed.

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Correlation between disease severity and in vitro cytokine production mediated by MSRV (Multiple Sclerosis associated RetroViral element) envelope protein in patients with multiple sclerosis

Cited by 71 publications

References 30 publications

Human Endogenous Retrovirus Expression Profiles in Samples from Brains of Patients with Schizophrenia and Bipolar Disorders

Human Endogenous Retrovirus Expression Profiles in Samples from Brains of Patients with Schizophrenia and Bipolar Disorders

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

Human RNA “Rumor” Viruses: the Search for Novel Human Retroviruses in Chronic Disease

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