Brains and peripheral blood mononuclear cells of multiple sclerosis (MS) patients hyperexpress MS-associated retrovirus/HERV-W endogenous retrovirus, but not Human herpesvirus 6.
Multiple sclerosis (MS)-associated retrovirus (MSRV)/HERV-W (human endogenous retrovirus W) and Human herpesvirus 6 (HHV-6) are the two most studied (and discussed) viruses as environmental co-factors that trigger MS immunopathological phenomena. Autopsied brain tissues from MS patients and controls and peripheral blood mononuclear cells (PBMCs) were analysed. Quantitative RT-PCR and PCR with primers specific for MSRV/HERV-W env and pol and HHV-6 U94/rep and DNA-pol were used to determine virus copy numbers. Brain sections were immunostained with HERV-W env-specific monoclonal antibody to detect the viral protein. All brains expressed MSRV/HERV-W env and pol genes. Phylogenetic analysis indicated that cerebral MSRV/HERV-W-related env sequences, plasmatic MSRV, HERV-W and ERVWE1 (syncytin) are related closely. Accumulation of MSRV/HERV-W-specific RNAs was significantly greater in MS brains than in controls (P=0.014 vs healthy controls; P=0.006 vs pathological controls). By immunohistochemistry, no HERV-W env protein was detected in control brains, whereas it was upregulated within MS plaques and correlated with the extent of active demyelination and inflammation. No HHV-6-specific RNAs were detected in brains of MS patients; one healthy control had latent HHV-6 and one pathological control had replicating HHV-6. At the PBMC level, all MS patients expressed MSRV/HERV-W env at higher copy numbers than did controls (P=0.00003). Similar HHV-6 presence was found in MS patients and healthy individuals; only one MS patient had replicating HHV-6. This report, the first to study both MSRV/HERV-W and HHV-6, indicates that MSRV/HERV-W is expressed actively in human brain and activated strongly in MS patients, whilst there are no significant differences between these MS patients and controls for HHV-6 presence/replication at the brain or PBMC level.
Mameli
Giuseppe
G
Section of Microbiology, Department of Biomedical Sciences, Center of Excellence for Biotechnology Development and Biodiversity Research, University of Sassari, Sassari, Italy.
Astone
Vito
V
Section of Microbiology, Department of Biomedical Sciences, Center of Excellence for Biotechnology Development and Biodiversity Research, University of Sassari, Sassari, Italy.
Arru
Giannina
G
Institute of Clinical Neurology, University of Sassari, Sassari, Italy.
Marconi
Silvia
S
Section of Neurology, Department of Neurological Sciences and Vision, University of Verona, Verona, Italy.
Lovato
Laura
L
Section of Neurology, Department of Neurological Sciences and Vision, University of Verona, Verona, Italy.
Serra
Caterina
C
Section of Microbiology, Department of Biomedical Sciences, Center of Excellence for Biotechnology Development and Biodiversity Research, University of Sassari, Sassari, Italy.
Sotgiu
Stefano
S
Institute of Clinical Neurology, University of Sassari, Sassari, Italy.
Bonetti
Bruno
B
Section of Neurology, Department of Neurological Sciences and Vision, University of Verona, Verona, Italy.
Dolei
Antonina
A
Section of Microbiology, Department of Biomedical Sciences, Center of Excellence for Biotechnology Development and Biodiversity Research, University of Sassari, Sassari, Italy.
D001921:Brain / Q000473:pathology / Q000821:virology*; D020077:Endogenous Retroviruses / Q000378:metabolism*; D015654:Herpesvirus 6, Human / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology*; D009103:Multiple Sclerosis / Q000097:blood / Q000821:virology*