Lactate dehydrogenase-elevating virus (LDV), a togavirus, naturally produces benign persistent infections characterized by continuous virus production in mice. Although, most isolates of LDV cause no overt disease in the mice they infect, one isolate, LDV-C, efficiently induces two distinct host strain specific diseases, poliomyelitis in C58 and AKR mice and meningitis and white matter inflammation in C57BR/cd mice. The LDV system provides a unique model for the study of genetically restricted host-virus interactions which lead to CNS neuropathology. The viral envelope (E) glycoprotein appears to be the key to understanding these complex host-virus interactions, since this protein should contain both the binding site for attachment to host cells and the immunodominant epitopes which elicit the host immune response. This proposal describes a study to characterize the LDV-E protein and to define its role in the induction of two different types of neuropathology. The E protein will be chemically characterized using glycosidase treatment and by amino acid and nucleic acid sequencing techniques. It will be analyzed antigenically using anti-E specific polyclonal and monoclonal antibodies. The in vitro B cell mitogenic activity of LDV and purified E protein will be evaluated. C58 mice appear to have LDV-specific receptors on their anterior motor neurons. We propose that while macrophages can be infected with either LDV or LDV-immune complexes, neurons can only be infected by LDV. To test this hypothesis, we will determine whether disease is more severe in B cell deficient c58 mice and conversely whether injection of anti-E antibody prior to infection reduces disease severity. Anti-E protein antibodies obtained during the proposed study may be useful for production of anti-idiotypic antibodies, which in turn could be used to localize and define virus- susceptible cell populations and virus receptors. Our preliminary data indicate that LDV-C infection of C57BR/cd mice may trigger an allergic encephalomyelitis response. We will attempt to induce this response in C57BR/cd mice in the absence of infection by immunization with purified E protein. The production of CNS tissue reactive autoantibodies by LDV-C infected mice will be investigated. The relative contribution of anti-E antibody or immune T cells to disease development will be investigated. Attempts will be made to infect cultured oligodendrocytes or astrocytes.
