Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2009 Nov 16:6:104.
doi: 10.1186/1742-4690-6-104.

B cells and monocytes from patients with active multiple sclerosis exhibit increased surface expression of both HERV-H Env and HERV-W Env, accompanied by increased seroreactivity

Affiliations

B cells and monocytes from patients with active multiple sclerosis exhibit increased surface expression of both HERV-H Env and HERV-W Env, accompanied by increased seroreactivity

Tomasz Brudek et al. Retrovirology. .

Abstract

Background: 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). Herpesviruses and human endogenous retroviruses (HERVs) represent potentially important factors in MS development. Herpesviruses can activate HERVs, and HERVs are activated in MS patients.

Results: Using 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.

Conclusion: These 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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Western blot analyses of OptiPrep purified HERV particles from MS 1946 long-term, lymphoblastoid cell cultures. Anti-HERV-H/-W Env TM and SU antibodies were raised in New Zealand white rabbits against 17-mer peptides localised at specific, but equivalent positions in the Env ORFs of HERV-H env62/H19 (Env H1TM: aa489-505; Env H3SU: aa 370-386) and of syncytin 1 (Env W1TM: aa415-431, Env W3SU: aa301-317). Size markers are shown to the left. TM, SU -- anti-HERV Env TM/SU serum; PTM, PSU -- appropriate pre-immune control sera. A. Flow cytometric analysis of surface expression of HERV-H Env and HERV-W Env TM and SU epitopes on cells from MS 1946 long-term lymphoblastoid cell cultures. The grey peaks represent the fluorescence of cells incubated with human IgG; the peaks with dashed line represent fluorescence of the cells incubated with pre-immune serum and FITC goat anti-rabbit antibodies; and the peaks with solid line represent fluorescence of the cells incubated with anti-HERV-H/-W Env TM/SU anti-sera and FITC goat anti-rabbit antibodies. Fluorescence indices are calculated as the ratio of the mean fluorescence of the cells incubated with anti-Env Abs to the mean fluorescence of the cells incubated with the appropriate control (pre-immune serum).
Figure 2
Figure 2
Flow cytometric analysis of surface expression of HERV-H Env and HERV-W Env on B-cells and monocytes from patients with active MS (AMS), stable MS patients (SMS), healthy individuals (HC), and neurological non-inflammatory controls (NC). The results are presented as fluorescence indices calculated as the ratio of the mean fluorescence of the cells incubated with anti-Env Abs to the mean fluorescence of the cells incubated with the appropriate control (pre-immune serum). Mean values (2A) and scatter plots (2C) for cells incubated with anti-Env TM Abs. Mean values (2B) and scatter plots (2D) for cells incubated with anti-Env SU Abs. The standard errors for each group are presented. The significant differences (P ≤ 0.05) between the groups are shown. * - P ≤ 0.05; ** - P ≤ 0.01; ***- P ≤ 0.001 on column bar graphs 2A and 2B.
Figure 3
Figure 3
Flow cytometric analysis of different leukocyte populations in PBMCs isolated from patients with active MS (AMS), stable MS patients (SMS), healthy individuals (HC), and neurological non-inflammatory controls (NC). The bars represent the percentage of CD19, CD4, CD8, and CD14 cells in 5 × 106 PBMCs. The mean values and the standard error for each group are presented, and the significant differences (P ≤ 0.05) between the groups are shown. * - P ≤ 0.05; ** - P ≤ 0.01; ***- P ≤ 0.001
Figure 4
Figure 4
Seroreactivity to HERV-H Env and HERV-W Env derived peptides in patients with active MS (AMS), stable MS patients (SMS), and healthy individuals (HC) and neurological non-inflammatory controls (NC). The horizontal lines indicate median TRIFMA ratios for each group. Significant differences (P ≤ 0.05) between the groups are shown.
Figure 5
Figure 5
Multiparameter regression between the levels of anti-HERV-H/-W Env blood serum antibodies measured by TRIFMA vs. the levels of surface expression of HERV-H Env and HERV-W Env epitopes on B-cells and monocytes from patients with active MS (AMS), stable MS patients (SMS), and healthy individuals (HC) measured by flow cytometry (expressed as fluorescence indices calculated as the ratio of the mean fluorescence of the cells incubated with anti-Env Abs to the mean fluorescence of the cells incubated with the appropriate control (pre-immune serum)). The solid line for CD19+ cells and dashed line for monocytes indicate the regression line. Correlation coefficient (r2) and statistical (P ≤ 0.05) significance are shown.

Similar articles

Cited by

References

    1. Noseworthy JH. Progress in determining the causes and treatment of multiple sclerosis. Nature. 1999;399:A40–A47. - PubMed
    1. Christensen T. Association of human endogenous retroviruses with multiple sclerosis and possible interactions with herpes viruses. Rev Med Virol. 2005;15:179–211. doi: 10.1002/rmv.465. - DOI - PubMed
    1. Simmons A. Herpesvirus and multiple sclerosis. Herpes. 2001;8:60–63. - PubMed
    1. Brudek T, Christensen T, Hansen HJ, Bobecka J, Moller-Larsen A. Simultaneous presence of endogenous retrovirus and herpes virus antigens has profound effect on cell-mediated immune responses: implications for multiple sclerosis. AIDS Res Hum Retroviruses. 2004;20:415–423. doi: 10.1089/088922204323048168. - DOI - PubMed
    1. Sutkowski N, Conrad B, Thorley-Lawson DA, Huber BT. Epstein-Barr Virus Transactivates the Human Endogenous Retrovirus HERV-K18 that Encodes a Superantigen. Immunity. 2001;15:579–589. doi: 10.1016/S1074-7613(01)00210-2. - DOI - PubMed

Publication types