High-avidity human serum antibodies recognizing linear epitopes of borna disease virus proteins

Background: The recent observation that Borna disease virus (BDV)–reactive antibodies from psychiatric patients exhibit only low avidity for BDV antigen called into question their diagnostic value and raised the possibility that antigenically related microorganisms or self antigens caused the production of these antibodies. We further characterized the specificity of these antibodies. Methods: We established a peptide array–based screening test that allows the identification of antibodies directed against linear epitopes of the two major BDV proteins, the nucleoprotein (N) and the phosphoprotein (P). Results: Initial tests employing sera of BDV-infected mice and rats or horses with Borna disease revealed a high specificity and sensitivity of this test. All sera recognized epitopes of N, P, or both. Sera of noninfected rats, mice, and horses showed no signals on either peptide array. Several human sera that recognized BDV antigen by indirect immunofluorescence contained antibodies that recognized various linear epitopes of one or even both BDV proteins. Remarkably, antibodies purified from such human serum by matrix-immobilized peptides showed high-avidity binding to BDV antigens when assayed by IFA or Western blotting. Conclusions: These data suggest that reactive antibodies found in psychiatric patients indeed indicate infection with BDV or a BDV-like agent. However, the poor affinity maturation of BDV-specific human antibodies remains unexplained.