Massive peptide sharing between viral and human proteomes

Abstract

Thirty viral proteomes were examined for amino acid sequence similarity to the human proteome, and, in parallel, a control of 30 sets of human proteins was analyzed for internal human overlapping. We find that all of the analyzed 30 viral proteomes, independently of their structural or pathogenic characteristics, present a high number of pentapeptide overlaps to the human proteome. Among the examined viruses, human T-lymphotropic virus 1, Rubella virus, and hepatitis C virus present the highest number of viral overlaps to the human proteome. The widespread and ample distribution of viral amino acid sequences through the human proteome indicates that viral and human proteins are formed of common peptide backbone units and suggests a fluid compositional chimerism in phylogenetic entities canonically classified distantly as viruses and Homo sapiens. Importantly, the massive viral to human peptide overlapping calls into question the possibility of a direct causal association between virus-host sharing of amino acid sequences and incitement to autoimmune reactions through molecular recognition of common motifs.

The Guillain–Barrè peptide signatures: from Zika virus to Campylobacter, and beyond

“…As previously observed, [64][65][66][67] such pentapeptide sharing is extremely high Table 1 Pentapeptides common to ZIKV, GBS-related human proteins, and GBS-related pathogens …”

“…Starting from 2000, 64 our laboratory described a massive peptide overlap between proteins from infectious agents and the human proteome, 65 thus calling attention to the cross-reactivity issue in immunology. In fact, the magnitude of such a peptide sharing leads to predict a high extent of cross-reactive immune responses following infections in the human host.…”

Bacterial peptides are intensively present throughout the human proteome

“…[8][9][10][11][12][13][14] In contrast, the results presented here are consistent with a number of other reports in which the elusive character of the molecular mimicry hypothesis has been underlined. [15][16][17][18][19][20][21][22][23][24][25][26][27] Our past 4,5 and present data tend to exclude a causal mechanistic role for molecular mimicry in the genesis of autoimmunity. According to the molecular mimicry hypothesis, the widespread overlap between viral and bacterial proteomes and the human proteome (see Table 1 and ref.…”

“…According to the molecular mimicry hypothesis, the widespread overlap between viral and bacterial proteomes and the human proteome (see Table 1 and ref. 5) would predict that autoimmune diseases should have a much higher incidence than actually observed, both in the total number of individuals affected and the number of autoimmune pathologies per individual. Thus, it is difficult to reconcile the enormous number of viral and bacterial peptides disseminated throughout the human proteins with a fundamental role for molecular mimicry in the etiology of certain autoimmune conditions.…”

“…[1][2][3] We recently analyzed a set of viral proteomes for sequence similarity to the human proteome, and reported a massive and widespread peptide overlapping between viral and human proteins. 4,5 Here we analyze a set of 20 pathogenic and 20 non-pathogenic bacterial proteomes, and report that all of the bacterial proteomes studied exhibit an unexpectedly high level of peptide sharing with the human proteome, irrespective of the microbe's pathogenicity.…”