Novel reliable real-time PCR for differential detection of MSRVenv and syncytin-1 in RNA and DNA from patients with multiple sclerosis

Mameli, Giuseppe; Poddighe, Luciana; Astone, Vito; Delogu, Giuseppe; Arru, Giannina; Sotgiu, Stefano; Serra, Caterina; Dolei, Antonina

doi:10.1016/j.jviromet.2009.05.024

Cited by 81 publications

(120 citation statements)

References 55 publications

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“…33 A subsequent study found a statistically significant 19% increase in MSRVenv DNA copies, influenced by gender and disease severity. 30 25 (b) Progression to the secondary progressive (SPMS) course within 10 years of early RRMS patients, according to presence/absence of HERV-W/MSRV genomic RNA in the spinal fluids at study entry; for details, see Sotgiu et al 26 (c) Circulating HERV-W/MSRV and disease outcome of MS patients, after 12 months of efficacious therapy with interferon β or natalizumab.…”

Section: Herv-w/msrvw/syncytin-1 Expression In Vivomentioning

confidence: 93%

The aliens inside us: HERV-W endogenous retroviruses and multiple sclerosis

Dolei

2018

Mult Scler

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Two human endogenous retroviruses of the HERV-W family are proposed as multiple sclerosis (MS) co-factors: MS-associated retrovirus (MSRV) and ERVWE1, whose env proteins showed several potentially neuropathogenic features, in vitro and in animal models. Phase II clinical trials against HERV-Wenv are ongoing. HERV-W/MSRV was repeatedly found in MS patients, in striking parallel with MS stages, active/remission phases, and therapy outcome. The HERV-Wenv protein is highly expressed in active MS plaques. Early MSRV presence in spinal fluids predicted worst MS progression 10 years in advance. Effective anti-MS therapies strongly reduced MSRV/Syncytin-1/HERV-W expression. The Epstein-Barr virus (EBV) activates HERV-W/MSRV in vitro and in vivo, in patients with infectious mononucleosis and controls with high anti-EBNA1-IgG titers. Thus, the two main EBV/MS links (infectious mononucleosis and high anti-EBNA1-IgG titers) are paralleled by activation of HERV-W/MSRV. It is hypothesized that EBV may act as initial trigger of future MS, years later, by activating MSRV, which would act as direct neuropathogenic effector, before and during MS.

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Section: Herv-w/msrvw/syncytin-1 Expression In Vivomentioning

confidence: 93%

The aliens inside us: HERV-W endogenous retroviruses and multiple sclerosis

Dolei

2018

Mult Scler

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“…Detection of retroviral sequences in patients with MS stimulated research on the association of those sequences with MS and a potential pathogenic role. MSRV was proposed to be an exogenous replication-competent member of the HERV-W group that might be involved in MS (15)(16)(17)(18)(19). However, the existence of MSRV as a replication-competent exogenous retrovirus seems to have little support, as closer inspection of the reported MSRV sequences strongly suggests that they either originated from existing genomic HERV-W loci or were generated in vitro by reverse transcriptase (RT) switching templates, i.e., RNA transcripts from different HERV-W loci (20), during the generation of cDNA.…”

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confidence: 99%

Comprehensive Analysis of Human Endogenous Retrovirus Group HERV-W Locus Transcription in Multiple Sclerosis Brain Lesions by High-Throughput Amplicon Sequencing

Schmitt

Richter

Backes

et al. 2013

J Virol

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“…By immunohistochemistry, no HERV-Wenv protein was detected in control brains, whereas it was highly expressed within MS plaques and correlated with the extent of active demyelination and inflammation. At the lesion edge, HERV-W immunostaining was detected on cells resembling both astrocytes and microglia, while in plaque centers, the HERV-W signal was mostly localized on hypertrophic astrocytes [29].…”

Section: Ms and Herv-wsmentioning

confidence: 98%

“…At the RNA level, MSRVenv and syncytin-1 have 94% similarity; we observed that MSRVenv sequences have a 12-nucleotide insertion in the trans-membrane moiety [29]. Based on this insertion, we developed discriminatory real-time polymerase chain reaction (PCR) assays that can amplify selectively either MSRVenv or syncytin-1 [29].…”

Section: The Herv-w Family: Msrv and Syncytin-1mentioning

confidence: 99%

“…However, due to the sequence similarities, effective distinction between the two elements by discriminatory quantitative real-time reverse transcription (RT)-PCR assays was carried out only by our group [24,[28][29]36] and later on, with the same assay, by Perron et al [37]. With the aid of these realtime PCR assays, which can amplify selectively either MSRVenv or syncytin-1 [29], we found that the DNA of MS patients had increased MSRVenv copies (sixfold mean increase, p = 0.02), while the syncytin-1-specific assay gave almost identical mean values for both patients and controls [29].…”

Section: Ms and Herv-wsmentioning

confidence: 99%

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The aliens inside human DNA: HERV-W/MSRV/syncytin-1 endogenous retroviruses and neurodegeneration

Dolei

Uleri

Ibba

et al. 2015

J Infect Dev Ctries

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The human genome contains remnants of ancestral retroviruses now endogenously transmitted, called human endogenous retroviruses (HERVs). HERVs can be variably expressed, and both beneficial and detrimental effects have described. This review focuses on the MSRV and syncytin-1 HERV-W elements in relationship to neurodegeneration in view of their neuro-pathogenic and immune-pathogenic properties. Multiple sclerosis (MS) and a neurodegenerative disease (neuroAIDS) are reported in this review. In vivo studies in patients and controls for molecular epidemiology and follow-up studies are reviewed, along with in vitro cellular studies of the effects of treatments and of molecular mechanisms. HERV-W/MSRV has been repeatedly found in MS patients (in blood, spinal fluid, and brain samples), and MRSV presence/load strikingly parallels MS stages and active/remission phases, as well as therapy outcome. The DNA of MS patients has increased MSRVenv copies, while syncytin-1 copies are unchanged in controls. Presence of MSRV in the spinal fluid predicted the worst MS progression, ten years in advance. The Epstein-Barr virus (EBV) activates HERV-W/MSRV both in vitro and in vivo. With respect to neuroAIDS, the HIV transactivator of transcription (Tat) protein activates HERV-W/MSRV in monocytes/macrophages and astrocytes indirectly by interaction with TLR4 and induction of TNF. HERV-W/MSRV can be considered a biomarker for MS behavior and therapy outcome. Regarding MS pathogenesis, we postulate the possibility for EBV of an initial trigger of future MS, years later, and for MSRV of a direct role of effector of neuropathogenesis during MS. Additionally, HERV-W/MSR/syncytin-1 activation by HIV Tat could contribute to the HIV-related neurodegeneration.

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Novel reliable real-time PCR for differential detection of MSRVenv and syncytin-1 in RNA and DNA from patients with multiple sclerosis

Cited by 81 publications

References 55 publications

The aliens inside us: HERV-W endogenous retroviruses and multiple sclerosis

The aliens inside us: HERV-W endogenous retroviruses and multiple sclerosis

Comprehensive Analysis of Human Endogenous Retrovirus Group HERV-W Locus Transcription in Multiple Sclerosis Brain Lesions by High-Throughput Amplicon Sequencing

The aliens inside human DNA: HERV-W/MSRV/syncytin-1 endogenous retroviruses and neurodegeneration

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