ENHANCEMENT OF AUTOIMMUNE-DISEASE USING RECOMBINANT VACCINIA VIRUS ENCODING MYELIN PROTEOLIPID PROTEIN

Viral infections have been associated with the initiation and exacerba tions often observed with autoimmune disease. Mechanisms by which viru ses may play a role in the development of autoreactive immune response s include polyclonal activation of B and T cells, molecular mimicry, v iral infection of immune cells, exposure of sequestered antigens, or a ltered host cell expression (neoantigen or altered self) in virus infe cted host cells. We have been studying the immune response generated t o self proteins in association with viral infection. Here we evaluate the effects of viral infection on the development of an autoimmune dis ease of the central nervous system, experimental allergic encephalomye litis. A vaccinia virus construct, VVplp was made containing the codin g region for rat myelin proteolipid protein (PLP). Cells infected with VVplp were found to express PLP protein in vitro. Central nervous sys tem disease was not detectable in mice vaccinated with VVplp. However, mice vaccinated with VVplp and later challenged with encephalitogenic peptides derived from PLP were found to have enhanced disease with ea rlier onset of symptoms when compared to mice treated with a control v accinia virus construct. This enhancement of disease was found to peak at 10 days post challenge with the encephalitogenic PLP peptide. Clin ical disease and an inflammatory response in the central nervous syste m was evident in mice previously vaccinated with VVplp but not in cont rol vaccinated mice at this time. These results indicate that prior in fection with a virus capable of coding for self protein can predispose the host to an accentuated autoimmune response.