title: High-avidity human serum antibodies recognizing linear epitopes of Borna disease virus proteins.
abstract: 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.
authors.affiliation: Department of Virology, Institute for Medical Microbiology and Hygiene, University of Freiburg, Freiburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Billich
authors.forename: Christian
authors.initials: C
authors.lastname: Sauder
authors.forename: Ronald
authors.initials: R
authors.lastname: Frank
authors.forename: Sibylle
authors.initials: S
authors.lastname: Herzog
authors.forename: Karl
authors.initials: K
authors.lastname: Bechter
authors.forename: Kazuo
authors.initials: K
authors.lastname: Takahashi
authors.forename: Helmut
authors.initials: H
authors.lastname: Peters
authors.forename: Peter
authors.initials: P
authors.lastname: Staeheli
authors.forename: Martin
authors.initials: M
authors.lastname: Schwemmle
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood*; D000915:Antibody Affinity; D000956:Antigens, Viral / Q000276:immunology*; D001890:Borna Disease / Q000097:blood / Q000150:complications / Q000175:diagnosis* / Q000276:immunology; D001891:Borna disease virus / Q000276:immunology*; D000939:Epitopes; D005260:Female; D005455:Fluorescent Antibody Technique; D006736:Horses; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000821:virology*; D051379:Mice; D015336:Molecular Probe Techniques; D051381:Rats; D012494:Sampling Studies
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D000939:Epitopes