title: An antibody response to human polyomavirus 15-mer peptides is highly abundant in healthy human subjects.
abstract: BACKGROUND
  Human polyomaviruses (HPyV) infections cause mostly unapparent or mild primary infections, followed by lifelong nonpathogenic persistence. HPyV, and specifically JCPyV, are known to co-diverge with their host, implying a slow rate of viral evolution and a large timescale of virus/host co-existence. Recent bio-informatic reports showed a large level of peptide homology between JCPyV and the human proteome. In this study, the antibody response to PyV peptides is evaluated.
  
  
  METHODS
  The in-silico analysis of the HPyV proteome was followed by peptide microarray serology. A HPyV-peptide microarray containing 4,284 peptides was designed and covered 10 polyomavirus proteomes. Plasma samples from 49 healthy subjects were tested against these peptides.
  
  
  RESULTS
  In-silico analysis of all possible HPyV 5-mer amino acid sequences were compared to the human proteome, and 1,609 unique motifs are presented. Assuming a linear epitope being as small as a pentapeptide, on average 9.3% of the polyomavirus proteome is unique and could be recognized by the host as non-self. Small t Ag (stAg) contains a significantly higher percentage of unique pentapeptides. Experimental evidence for the presence of antibodies against HPyV 15-mer peptides in healthy subjects resulted in the following observations: i) antibody responses against stAg were significantly elevated, and against viral protein 2 (VP2) significantly reduced; and ii) there was a significant correlation between the increasing number of embedded unique HPyV penta-peptides and the increase in microarray fluorescent signal.
  
  
  CONCLUSIONS
  The anti-peptide HPyV-antibodies in healthy subjects are preferably directed against the penta-peptide derived unique fraction of the viral proteome.
authors.affiliation: Janssen Diagnostics, Turnhoutsebaan 30, Beerse, B-2340, Belgium. lstuyver@its.jnj.com
authors.forename: Lieven J
authors.initials: LJ
authors.lastname: Stuyver
authors.forename: Tobias
authors.initials: T
authors.lastname: Verbeke
authors.forename: Tom
authors.initials: T
authors.lastname: Van Loy
authors.forename: Ellen
authors.initials: E
authors.lastname: Van Gulck
authors.forename: Luc
authors.initials: L
authors.lastname: Tritsmans
mesh_terms: D000328:Adult; D000914:Antibodies, Viral / Q000097:blood*; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology*; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011120:Polyomavirus / Q000235:genetics / Q000276:immunology*; D040081:Protein Array Analysis; D017422:Sequence Analysis, DNA; D016036:Seroepidemiologic Studies; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D004279:DNA, Viral; D014764:Viral Proteins