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.