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.
|Full text disponibile come PDF Richiede visualizzatore di PDF come GSview, Xpdf o Adobe Acrobat Reader |
Available under License Creative Commons Attribution.
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.
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
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.
I documenti depositati in UnissResearch sono protetti dalle leggi che regolano il diritto d'autore
Repository Staff Only: item control page