antibody response to human polyomavirus 15-mer peptides is highly abundant in healthy human subjects

• Published in: Virology journal Vol. 10; no. 1; p. 192
• Main Authors: Stuyver, Lieven J, Verbeke, Tobias, Van Loy, Tom, Van Gulck, Ellen, Tritsmans, Luc
• Format: Journal Article
• Language: English
• Published: England Springer-Verlag 12.06.2013; BioMed Central Ltd; BioMed Central
• Subjects: Adult; amino acid sequences; antibodies; Antibodies, Viral - blood; Antigens, Viral - genetics; Antigens, Viral - immunology; Development and progression; DNA, Viral - chemistry; DNA, Viral - genetics; epitopes; evolution; Female; fluorescence; Genomes; Health aspects; human health; Humans; Male; Methods; microarray technology; Middle Aged; Molecular Sequence Data; Peptides; Polyoma virus; Polyomaviridae; Polyomavirus; Polyomavirus - genetics; Polyomavirus - immunology; Protein Array Analysis; Proteins; proteome; Risk factors; Sequence Analysis, DNA; Seroepidemiologic Studies; serology; Viral proteins; Viral Proteins - genetics; Viral Proteins - immunology; Virus diseases; Viruses; Young Adult; Germany
• ISSN: 1743-422X; 1743-422X
• DOI: 10.1186/1743-422X-10-192

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. CONCLUSION: The anti-peptide HPyV-antibodies in healthy subjects are preferably directed against the penta-peptide derived unique fraction of the viral proteome.