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Expression and activation of human endogenous retroviruses of the W family in blood cells and astrocytes: implications for the pathogenesis of multiple sclerosis

Poddighe, Luciana and Mameli, Giuseppe and Mei, Alessandra and Uleri, Elena and Serra, Caterina and Manetti, Roberto and Dolei, Antonina (2011) Expression and activation of human endogenous retroviruses of the W family in blood cells and astrocytes: implications for the pathogenesis of multiple sclerosis. Retrovirology, Vol. 8 (Suppl. 2), P19. eISSN 1742-4690. Article.

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DOI: 10.1186/1742-4690-8-S2-P19

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Abstract

Background
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system, with demyelination and gliosis. Proposed pathogenic co-factors triggering MS pathogenesis are the Epstein Barr virus (EBV), and two elements of the W family of human endogenous retroviruses (HERV-W): MSRV, that forms free virions, and syncytin-1, the ERVWE1env protein; both retroelements have neuropathogenic properties. In the past we studied MSRV in MS patients in various temporal and clinical stages; in all cases, striking parallelisms between MS behaviour and MSRV/HERV-W presence/ load were found. By simultaneous detection of MSRV and HHV-6, we found a direct correlation between MS and MSRV presence/load, but not for HHV-6. MS brains over-express MSRVenv and syncytin-1 transcripts, with respect to controls, while EBV presence was not detected.
Materials and methods
Since late EBV seroconversion is a strong risk factor for MS development, we performed in vitro experiments on PBMC from MS patients and MSRV+ volunteers, as well as on U87-MG astroglioma cells, that were studied as such or were exposed to EBV or to recombinant EBV glycoprotein350 (EBVgp350), or to proinflammatory cytokines. The levels of MSRVenv and syncytin-1 mRNAs were evaluated by discriminatory real time RTPCR assays. Flow cytometry was used to evaluate the HERV-Wenv protein on the plasmamembrane, as well the PBMC subsets.
Results
Basal expression of MSRVenv and syncytin-1 occurs in astrocytes and in NK, B and monocyte cells, but not in T cells. This uneven expression is amplified in naive MS patients. Astrocyte infection by EBV and exposure to EBVgp350 stimulate the expression of HERV-W/MSRV/ syncytin-1, with requirement of the NF-kB pathway. In EBVgp350-treated PBMC, MSRVenv and syncytin-1 are activated in B cells and monocytes, but not in T cells, nor in the highly expressing NK cells. The latter cells, but not the T cells, are activated by proinflammatory cytokines.
Conclusions
The study demonstrates that there are interactions among the above proposed MS-cofactors. In vivo, a pathogenic outcome would depend on activation in abnormal situations/tissues, as it may occur in delayed EBV infection, or in the presence of particular host genetic backgrounds, or both.

Item Type:Article
ID Code:7615
Status:Published
Refereed:Yes
Uncontrolled Keywords:Multiple sclerosis (MS), Epstein Barr virus (EBV), W family of human endogenous retroviruses (HERV-W)
Subjects:Area 06 - Scienze mediche > MED/07 Microbiologia e microbiologia clinica
Divisions:001 Università di Sassari > 01 Dipartimenti > Scienze biomediche
Publisher:BioMed Central
eISSN:1742-4690
Copyright Holders:© 2011 Poddighe et al; licensee BioMed Central Ltd.
Additional Information:Poster presented at Frontiers of Retrovirology conference, Amsterdam, 3-5 October 2011.
Deposited On:05 Apr 2013 11:35

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