Antibodies against a human endogenous retrovirus and the preponderance of env splice variants in multiple sclerosis patients.
The human endogenous retrovirus HERV-H is associated with multiple sclerosis (MS). Previously performed reverse transcriptase-polymerase chain reactions (RT-PCR) on virion-RNA demonstrated sequence variants of the HERV-H family located in the particulate fraction of MS patient plasma samples and not in controls. In this study a significantly elevated level of antibodies towards peptides derived from HERV-H/RGH-2 DNA sequences in serum and cerebrospinal fluid (CSF) from MS patients is demonstrated. Further, Wistar rats immunized with purified virions develop a specific serologic response, indicating that some virion proteins are encoded by HERV-H-related sequences. Also shown is that in RNA from blood cells, a HERV-H protease-env splice variant can be found together with an env splice variant in about 40% of MS patients but only in 10% of controls. The results substantiate the association between activated HERV-H and MS, but a causal relationship is yet to be demonstrated. HERV-H could represent a causal factor either by eliciting an autoimmune response or through the pathogenic potential of the retrovirus itself.
Christensen
T
T
Department of Medical Microbiology and Immunology, University of Aarhus, DK-8000 Aarhus C, Denmark. tc@microbiology.au.dk
Sørensen
P D
PD
Hansen
H J
HJ
Møller-Larsen
A
A
D000328:Adult; D000368:Aged; D017398:Alternative Splicing / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology / Q000821:virology; D015415:Biomarkers; D017124:Conserved Sequence; D020077:Endogenous Retroviruses / Q000276:immunology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000276:immunology* / Q000821:virology; D051381:Rats; D017208:Rats, Wistar; D014759:Viral Envelope Proteins / Q000276:immunology*
D000914:Antibodies, Viral; D015415:Biomarkers; D014759:Viral Envelope Proteins