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Abstract
BackgroundThe etiology of the neurogenerative disease multiple sclerosis (MS) is unknown. The leading hypotheses suggest that MS is the result of exposure of genetically susceptible individuals to certain environmental factor(s). Herpesviruses and human endogenous retroviruses (HERVs) represent potentially important factors in MS development. Herpesviruses can activate HERVs, and HERVs are activated in MS patients.ResultsUsing flow cytometry, we have analyzed HERV-H Env and HERV-W Env epitope expression on the surface of PBMCs from MS patients with active and stable disease, and from control individuals. We have also analyzed serum antibody levels to the expressed HERV-H and HERV-W Env epitopes. We found a significantly higher expression of HERV-H and HERV-W Env epitopes on B cells and monocytes from patients with active MS compared with patients with stable MS or control individuals. Furthermore, patients with active disease had relatively higher numbers of B cells in the PBMC population, and higher antibody reactivities towards HERV-H Env and HERV-W Env epitopes. The higher antibody reactivities in sera from patients with active MS correlate with the higher levels of HERV-H Env and HERV-W Env expression on B cells and monocytes. We did not find such correlations for stable MS patients or for controls.ConclusionThese findings indicate that both HERV-H Env and HERV-W Env are expressed in higher quantities on the surface of B cells and monocytes in patients with active MS, and that the expression of these proteins may be associated with exacerbation of the disease.
Highlights
The etiology of the neurogenerative disease multiple sclerosis (MS) is unknown
Western Blot and flow cytometric analyses of human endogenous retroviruses (HERVs)-H Env and HERV-W Env expression on the surface of cells and particles obtained from MS cell cultures The polyclonal anti-HERV-H/-W Env TM and SU rabbit antibodies were used in Western Blot analyses of purified retroviral particles from MS1946 cell culture, to detect whether these Env epitopes are present on virion surfaces
The polyclonal anti-HERV-H/-W Env antibodies were raised towards equivalent but specific peptide epitopes: two peptides were localized in the TM regions of HERV-H and HERV-W Envs, respectively, and two peptides were localized in the SU regions
Summary
The etiology of the neurogenerative disease multiple sclerosis (MS) is unknown. The leading hypotheses suggest that MS is the result of exposure of genetically susceptible individuals to certain environmental factor(s). Among the environmental factors human endogenous retroviruses (HERV) and the ubiquitously present herpesviruses are gaining growing attention, substantiated by an increasing number of reports suggesting their association (page number not for citation purposes). The cellular immune responses were synergistic in character and tended to be higher in MS patients in comparison with healthy controls. This in vitro observation is pertinent only if herpesvirus and HERV antigens are concurrently present in vivo in MS patients. We have recently shown that the presence of inactivated herpesviruses can activate expression of HERVs in particle form in PBMCs from MS patients in vitro, most probably resulting in the concurrent presence of these two types of virus [9]
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