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HHV-6 A- or B-specific P41 antigens do not reveal virus variant-specific IgG or IgM responses in human serum
Yunhe Xu1, Annika Linde, Sten Fredrikson
1Department of Virology, Swedish Institute for Infectious Disease Control, Solna, Sweden. Yunhe.Xu@cgb.ki.se
Abstract:
The etiology of multiple sclerosis (MS) remains unknown, but there are indications of a role of human herpesvirus 6 (HHV-6), especially variant A, in the pathogenesis. Higher serum antibody reactivity against an HHV-6 early protein, p41, has been found in MS cases than in controls. The antigen, however, was purified from infected cells with a monoclonal antibody also reactive with a protein (p38) likely to be of cellular origin. To avoid serological crossreactivity with the cellular protein, recombinant p41 proteins from HHV-6A strain GS and HHV-6B strain Z29 were expressed as glutathione-S-transferase fusion proteins (p41-GST), and used as antigens in an enzyme-linked immunosorbent assay (ELISA). p41 variant specific monoclonal antibodies reacted strongly with the respective recombinant proteins. Serum IgM and IgG reactivities with the recombinant p41 antigens were analysed in patients with manifest MS, patients with optic neuritis, patients with other neurological diseases, and in one group of healthy controls. All sera were HHV-6 IgG seropositive by immunofluorescence. The serum IgM or IgG reactivities against the recombinant p41 antigens did not differ significantly between the groups, and the reactivities against the variant A and B antigens were identical. In many samples, the reactivity was very low. The results indicate that p41 is not an optimal target for HHV-6 serology studies, and that the data obtained with the p41 antigen prepared from infected cells (possibly including also p38) should be interpreted with caution.
Insights
Human herpesvirus 6 (HHV-6) p41 protein is not an optimal target for multiple sclerosis (MS) serology. Studies using p41 from infected cells may yield inaccurate results due to cross-reactivity.
Area of Science:
- Neurovirology
- Immunology
- Infectious Diseases
Background:
- The role of human herpesvirus 6 (HHV-6) in multiple sclerosis (MS) pathogenesis is under investigation.
- Previous studies suggested higher antibody reactivity to HHV-6 early protein p41 in MS patients.
Purpose of the Study:
- To evaluate the diagnostic utility of recombinant HHV-6A and HHV-6B p41 proteins as antigens for serological studies in MS.
- To address potential cross-reactivity issues with cellular proteins in previous p41 antigen preparations.
Main Methods:
- Recombinant glutathione-S-transferase fusion proteins (p41-GST) of HHV-6A and HHV-6B were expressed and purified.
- Enzyme-linked immunosorbent assay (ELISA) was used to measure serum IgM and IgG reactivity against recombinant p41 antigens.
- Sera from MS patients, optic neuritis patients, other neurological disease patients, and healthy controls were analyzed.
Main Results:
- Monoclonal antibodies specific to p41 variants reacted strongly with the respective recombinant proteins.
- No significant differences in serum IgM or IgG reactivity against recombinant p41 antigens were observed between patient groups and controls.
- Reactivity against HHV-6A and HHV-6B p41 antigens was identical, and often low across all groups.
Conclusions:
- The HHV-6 p41 protein is not an optimal target for serological diagnosis of MS.
- Previous findings using p41 antigens purified from infected cells may require re-evaluation due to potential cross-reactivity with cellular proteins like p38.