Lack of immune responses against multiple sclerosis-associated retrovirus/human endogenous retrovirus W in patients with multiple sclerosis.

ABSTRACT

The multiple sclerosis-associated retrovirus (MSRV), originally identified in cell cultures from patients with multiple sclerosis (MS), is closely related to the human endogenous retrovirus family type W (HERV-W). Different lines of evidence appear compatible with a potential role of MSRV/HERV-W in the pathogenesis of MS. The authors therefore analyzed humoral and cellular immune responses against MSRV/HERV-W antigens in patients with MS, patients with other inflammatory and noninflammatory neurological diseases, and healthy controls, using indirect immunofluorescence and enzyme-linked immunospot assays. Antibodies against the HERV-W envelope (Env) protein, Syncytin-1, were found in one of 50 patients with MS and none of 59 controls, whereas antibodies against MSRV matrix and capsid (Gag) or Env proteins were not detectable in any of the patients or controls. Similarly, in a screening of human leukocyte antigen (HLA)-B7+ patients with MS (n = 23) and controls (n = 29) for cytotoxic T-lymphocyte responses against 36 predicted HLA-B7-restricted MSRV/HERV-W Gag-, protease-, and reverse transcriptase-derived peptides, no such responses could be detected in any of the subjects studied. These data suggest that there are no appreciable humoral or cellular immune responses against MSRV/HERV-W in patients with MS. While this may be due to immunological tolerance of physiologically expressed HERV-W proteins, strategies other than measurement of immune responses will be required to further elucidate the relationship between MSRV/HERV-W and MS.