Abstract

BackgroundHuman 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.MethodsThe 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.ResultsIn-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.ConclusionThe anti-peptide HPyV-antibodies in healthy subjects are preferably directed against the penta-peptide derived unique fraction of the viral proteome.

Highlights

  • Human polyomaviruses (HPyV) infections cause mostly unapparent or mild primary infections, followed by lifelong nonpathogenic persistence

  • The viral proteins large T antigen (LTAg), small T antigen (stAg), viral protein-1 (VP1), and VP2 for 11 HPyV were cut in silico into either 5-mer (with 4 amino acid overlap), 6-mer, or 7-mer peptides

  • The evidence collected for stAg in this paper showed some specific features for this viral protein, suggesting that the protein has not evolved towards a higher percentage of “host self” (Figure 1b, 16.6% of unique pentapeptides), and thereby maintaining an elevated level of immune presentation and antibody generation against linear epitopes (Figure 2)

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Summary

Introduction

Human polyomaviruses (HPyV) infections cause mostly unapparent or mild primary infections, followed by lifelong nonpathogenic persistence. HPyV, and 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. The antibody response to PyV peptides is evaluated. The Polyomaviridae Study Group of the International Committee on Taxonomy of Viruses (ICTV) has proposed that the Polyomaviridae family will be comprised of three genera: two genera containing mammalian viruses (Orthopolyomavirus and Wukipolyomavirus) and one genus containing avian viruses (Avipolyomavirus) [1]. Besides the HPyVs that were discovered more than 40 years ago (JCPyV and BKPyV), several new polyomaviruses have been discovered might explain the previously observed serological evidence that LPyV-like virus infections may occur in humans [15,16]

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