Production of monospecific antibody to immunodominant epitopes of the caprine arthritis encephalitis virus transmembrane glycoprotein and analysis of their activity in vitro

Abstract

Caprine arthritis encephalitis virus (CAEV)-infected goats develop high titers of nonneutralizing antibody to several immunodominant epitopes of the viral envelope glycoprotein. Antibodies directed to these structures, and especially the principal immunodominant domain (PID) of the transmembrane portion of the envelope glycoprotein, have been implicated in the immunopathological mechanisms leading to the development of arthritis. We previously mapped the PID and additional epitopes of CAEV gp38 and showed an association between the development of clinical arthritis in infected animals and the antibody response to these epitopes. The development of clinical arthritis is associated with a higher rate of viral expression, especially in the affected tissue, indicating that antibody may favorably modulate virus replication. To test this hypothesis, we immunized goats with synthetic peptides corresponding to the mapped epitopes. The immunized animals developed high titers of nonneutralizing antibody to the immunizing peptides. In radioimmunoprecipitation experiments these antibodies were shown to react to the envelope glycoproteins in extracts obtained under nondenaturing conditions. Finally, these sera were tested in cultures of primary macrophages infected at low multiplicity without showing any (either positive or negative) modulatory activity.