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Activation of MSRV-type endogenous retroviruses during infectious mononucleosis and Epstein-Barr virus latency: the missing link with multiple sclerosis?

Mameli, Giuseppe and Madeddu, Giordano and Mei, Alessandra and Uleri, Elena and Poddighe, Luciana and Delogu, Lucia Gemma and Maida, Ivana Rita and Babudieri, Sergio and Serra, Caterina and Manetti, Roberto and Mura, Maria Stella Anna and Dolei, Antonina (2013) Activation of MSRV-type endogenous retroviruses during infectious mononucleosis and Epstein-Barr virus latency: the missing link with multiple sclerosis? PLoS One, Vol. 8 (11), e78474. eISSN 1932-6203. Article.

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DOI: 10.1371/journal.pone.0078474

Abstract

The etiology of multiple sclerosis (MS) is still unclear. The immuno-pathogenic phenomena leading to neurodegeneration are thought to be triggered by environmental (viral?) factors operating on predisposing genetic backgrounds. Among the proposed co-factors are the Epstein Barr virus (EBV), and the potentially neuropathogenic HERV-W/MSRV/Syncytin-1 endogenous retroviruses. The ascertained links between EBV and MS are history of late primary infection, possibly leading to infectious mononucleosis (IM), and high titers of pre-onset IgG against EBV nuclear antigens (anti-EBNA IgG). During MS, there is no evidence of MS-specific EBV expression, while a continuous expression of HERV-Ws occurs, paralleling disease behaviour. We found repeatedly extracellular HERV-W/MSRV and MSRV-specific mRNA sequences in MS patients (in blood, spinal fluid, and brain samples), and MRSV presence/load strikingly paralleled MS stages and active/remission phases. Aim of the study was to verify whether HERV-W might be activated in vivo, in hospitalized young adults with IM symptoms, that were analyzed with respect to expression of HERV-W/MSRV transcripts and proteins. Healthy controls were either EBV-negative or latently EBV-infected with/without high titers of anti-EBNA-1 IgG. The results show that activation of HERV-W/MSRV occurs in blood mononuclear cells of IM patients (2Log10 increase of MSRV-type env mRNA accumulation with respect to EBV-negative controls). When healthy controls are stratified for previous EBV infection (high and low, or no anti-EBNA-1 IgG titers), a direct correlation occurs with MSRV mRNA accumulation. Flow cytometry data show increased percentages of cells exposing surface HERV-Wenv protein, that occur differently in specific cell subsets, and in acute disease and past infection. Thus, the data indicate that the two main links between EBV and MS (IM and high anti-EBNA-1-IgG titers) are paralleled by activation of the potentially neuropathogenic HERV-W/MSRV. These novel findings suggest HERV-W/MSRV activation as the missing link between EBV and MS, and may open new avenues of intervention.

Item Type:Article
ID Code:9591
Status:Published
Refereed:Yes
Uncontrolled Keywords:Antibodies, blood, cell membranes, cerebrospinal fluid, membrane proteins, multiple sclerosis, protein expression, viral pathogens
Subjects:Area 06 - Scienze mediche > MED/17 Malattie infettive
Area 06 - Scienze mediche > MED/07 Microbiologia e microbiologia clinica
Area 06 - Scienze mediche > MED/09 Medicina interna
Divisions:001 Università di Sassari > 01-a Nuovi Dipartimenti dal 2012 > Scienze Biomediche
001 Università di Sassari > 01-a Nuovi Dipartimenti dal 2012 > Chimica e Farmacia
001 Università di Sassari > 01-a Nuovi Dipartimenti dal 2012 > Medicina Clinica e Sperimentale
Publisher:Public Library of Science
eISSN:1932-6203
Copyright Holders: 2013 Mameli et al.
Deposited On:30 Jan 2014 13:35

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