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      Massive peptide sharing between viral and human proteomes

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          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.

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          Most cited references19

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          Molecular mimicry and immune‐mediated diseases

          Molecular mimicry has been proposed as a pathogenetic mechanism for autoimmune disease, as well as a probe useful in uncovering its etiologic agents. The hypothesis is based in part on the abundant epidemiological, clinical, and experimental evidence of an association of infectious agents with autoimmune disease and observed cross‐reactivity of immune reagents with host ‘self’ antigens and microbial determinants. For our purpose, molecular mimicry is defined as similar structures shared by molecules from dissimilar genes or by their protein products. Either the molecules' linear amino acid sequences or their conformational fits may be shared, even though their origins are as separate as, for example, a virus and a normal host–self determinant. An immune response against the determinant shared by the host and virus can evoke a tissue‐specific immune response that is presumably capable of eliciting cell and tissue destruction. The probable mechanism is generation of cytotoxic cross‐reactive effector lymphocytes or antibodies that recognize specific determinants on target cells. The induction of cross‐reactivity does not require a replicating agent, and immune‐mediated injury can occur after the immunogen has been removed—a hit‐and‐run event. Hence, the viral or microbial infection that initiates the autoimmune phenomenon may not be present by the time overt disease develops. By a complementary mechanism, the microbe can induce cellular injury and release self antigens, which generate immune responses that cross‐react with additional but genetically distinct self antigens. In both scenarios, analysis of the T cells or antibodies specifically engaged in the autoimmune response and disease provides a fingerprint for uncovering the initiating infectious agent.—Oldstone, M. B. A. Molecular mimicry and immune‐mediated diseases. FASEB J. 12, 1255–1265 (1998)
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            Generation of protein-reactive antibodies by short peptides is an event of high frequency: implications for the structural basis of immune recognition.

            Recent studies have shown that chemically synthesized small peptides can induce antibodies that often react with intact proteins regardless of their position in the folded molecule. These findings are difficult to explain in view of the experimental and theoretical data which suggest that in the absence of forces provided by the folded protein, small peptides in aqueous solution do not readily adopt stable structures. In order to rationalize the two findings, there has been general acceptance of a stochastic model which suggests that the multiple conformers of a peptide in solution induce sets of antibodies with a small percentage reactive with conformations shared by the folded protein. This stochastic model has become less tenable as the success rate for the generation of protein-reactive anti-peptide antibodies has grown. To test the stochastic model, we have used monoclonal anti-peptide antibodies as a way of estimating the frequency with which small peptides induce antibodies that react with folded proteins. We have made monoclonal antibodies to six chemically synthesized peptides from three proteins. The frequency with which the peptides induce protein-reactive antibodies is at least 4 orders of magnitude greater than expected from previous experimental work and vastly different from what would be predicted by calculating the possible number of peptide conformers in solution. These findings make the stochastic model less likely and lead to consideration of other models. Aside from their practical significance for generation of highly specific reagents, these findings may have important implications for the protein folding problem.
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              Peptidology: short amino acid modules in cell biology and immunology.

              Short amino acid motifs, either linear sequences or discontinuous amino acid groupings, can interact with specific protein domains, so exerting a central role in cell adhesion, signal transduction, hormone activity, regulation of transcript expression, enzyme activity, and antigen-antibody interaction. Here, we analyze the literature for such critical short amino acid motifs to determine the minimal peptide length involved in biologically important interactions. We report the pentapeptide unit as a common minimal amino acid sequence critically involved in peptide-protein interaction and immune recognition. The present survey may have implications in defining the dimensional module for peptide-based therapeutical approaches such as the development of novel antibiotics, enzyme inhibitors/activators, mimetic agonists/antagonists of neuropeptides, thrombolitic agents, specific anti-viral agents, etc. In such a therapeutical context, it is of considerable interest that low molecular weight peptides can easily cross biological barriers, are less susceptible to protease attacks, and can be administered at high concentrations. In addition, small peptides are a rational target for strategies aimed at antigen-specific immunotherapeutical intervention. As an example, specific short peptide fragments might be used to elicit antibodies capable of reacting with the full-length proteins containing the peptide fragment's amino acid sequence, so abolishing the risk of cross-reactivity.
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                Author and article information

                Contributors
                Journal
                Peptides
                Peptides
                Peptides
                Elsevier Inc.
                0196-9781
                1873-5169
                5 June 2008
                October 2008
                5 June 2008
                : 29
                : 10
                : 1755-1766
                Affiliations
                [a ]Department of Biochemistry and Molecular Biology, University of Bari, Bari 70126, Italy
                [b ]Department of Computer Science, University of Saskatchewan, Saskatoon, Canada
                Author notes
                [* ] Corresponding author. Tel.: +39 080 544 3321; fax: +39 080 544 3321. d.kanduc@ 123456biologia.uniba.it dkanduc@ 123456gmail.com
                Article
                S0196-9781(08)00254-4
                10.1016/j.peptides.2008.05.022
                7115663
                18582510
                3a9851f0-3176-45b4-a679-269ed7a8fa62
                Copyright © 2008 Elsevier Inc. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 29 February 2008
                : 28 May 2008
                : 30 May 2008
                Categories
                Article

                Biochemistry
                viral proteomes,human proteome,sequence similarity,peptide sharing,autoimmunity
                Biochemistry
                viral proteomes, human proteome, sequence similarity, peptide sharing, autoimmunity

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