Lack of Molecular Mimicry between Nonhuman Primates and Infectious Pathogens: The Possible Genetic Bases

Abstract

Recently, it was found that proteomes from poliovirus, measles virus, dengue virus, and severe acute respiratory syndrome-related Coronavirus 2 (SARS-CoV-2) have high molecular mimicry at the heptapeptide level with the human proteome, while heptapeptide commonality is minimal or absent with proteomes from nonhuman primates, that is, gorilla, chimpanzee, and rhesus macaque. To acquire more data on the issue, analyses here have been expanded to Ebola virus, Francisella tularensis, human immunodeficiency virus-1 (HIV-1), Toxoplasma gondii, Variola virus, and Yersinia pestis. Results confirm that heptapeptide overlap is high between pathogens and Homo sapiens, but not between pathogens and primates. Data are discussed in light of the possible genetic bases that differently model primate phenomes, thus possibly underlying the zero/low level of molecular mimicry between infectious agents and primates. Notably, this study might help address preclinical vaccine tests that currently utilize primates as animal models, since autoimmune cross-reactions and the consequent adverse events cannot occur in absentia of shared sequences.

Keywords

infectious agents / peptide sharing / molecular mimicry / cross-reactivity / autoimmunity / nonhuman primates / rhesus macaque / vaccines / preclinical test

References

[1] Natale C, Giannini T, Lucchese A, Kanduc D.Computer-assisted analysis ofmolecular mimicry between human papillomavirus 16 E7 oncoprotein and human protein sequences. Immunol Cell Biol 2000;78(06):580-585

[2] Kanduc D, Stufano A, Lucchese G, Kusalik A.Massive peptide sharing between viral and human proteomes. Peptides 2008;29(10):1755-1766

[3] Trost B, Lucchese G, Stufano A, Bickis M, Kusalik A, Kanduc D.No human protein is exempt frombacterial motifs, not even one. Self Nonself 2010;1(04):328-334

[4] Lucchese G, Kanduc D.Zika virus and autoimmunity: from microcephaly to Guillain-Barré syndrome, and beyond. Autoimmun Rev 2016;15(08):801-808

[5] Kanduc D, Shoenfeld Y.Inter-pathogen peptide sharing and the original antigenic sin: Solving a paradox. Open Immunol J 2018; 8:11-27

[6] Lucchese G.Confronting JC virus and Homo sapiens biological signatures. Front Biosci 2013;18:716-724

[7] Kanduc D.HCV: Written in our DNA. Self Nonself 2011;2(02): 108-113

[8] Kanduc D.Describing the hexapeptide identity platformbetween the influenza A H5N1 and Homo sapiens proteomes. Biologics 2010;4:245-261

[9] Lucchese A, Serpico R, Crincoli V, Shoenfeld Y, Kanduc D.Sequence uniqueness as a molecular signature of HIV-1-derived B-cell epitopes. Int J Immunopathol Pharmacol 2009;22(03): 639-646

[10] Kanduc D.From anti-SARS-CoV-2 immune responses to COVID-19 via molecular mimicry. Antibodies (Basel) 2020;9(03):E33

[11] Kanduc D.Peptide cross-reactivity: the original sin of vaccines. Front Biosci (Schol Ed) 2012;4:1393-1401

[12] Kanduc D.From influenza infection to anti-ADAMTS13 autoantibodies via cross-reactivity. Infect Int 2019;7:113-120

[13] Kanduc D.Describing the potential crossreactome between mumps virus and spermatogenesis-associated proteins. Endocr Metab Immune Disord Drug Targets 2014;14(03):218-225

[14] Lucchese G, Capone G, Kanduc D.Peptide sharing between influenza A H1N1 hemagglutinin and human axon guidance proteins. Schizophr Bull 2014;40(02):362-375

[15] Lucchese G.Understanding neuropsychiatric diseases, analyzing the peptide sharing between infectious agents and the language-associated NMDA 2A protein. Front Psychiatry 2016; 7:60

[16] Lucchese G.From toxoplasmosis to schizophrenia via NMDA dysfunction: peptide overlap between Toxoplasma gondii and N-Methyl-d-Aspartate Receptors as a potential mechanistic link. Front Psychiatry 2017;8:37

[17] Lucchese G, Kanduc D.Single amino acid repeats connect viruses to neurodegeneration. Curr Drug Discov Technol 2014;11(03): 214-219

[18] Kanduc D, Shoenfeld Y.From anti-EBV immune responses to the EBV diseasome via cross-reactivity. Glob Med Genet 2020;7(02): 51-63

[19] Kanduc D.Potential cross-reactivity between HPV16 L1 protein and sudden death-associated antigens. J Exp Ther Oncol 2011;9(02):159-165

[20] Capone G, Kanduc D.Peptide sharing between Bordetella pertussis proteome and human sudden death proteins: a hypothesis for a causal link. Future Microbiol 2013;8(08):1039-1048

[21] Kanduc D, Shoenfeld Y.Human papillomavirus epitope mimicry and autoimmunity: the molecular truth of peptide sharing. Pathobiology 2019;86(5-6):285-295

[22] Kanduc D.Influenza and sudden unexpected death: the possible role of peptide cross-reactivity. Infect Int 2019;7:121-131

[23] Kanduc D, Shoenfeld Y.On the molecular determinants of the SARS-CoV-2 attack. Clin Immunol 2020;215:108426

[24] Kanduc D.Measles virus hemagglutinin epitopes are potential hotspots for crossreactions with immunodeficiency-related proteins. Future Microbiol 2015;10(04):503-515

[25] Kanduc D, Polito A.From viral infections to autistic neurodevelopmental disorders via cross-reactivity. J Psychiatry Brain Sci 2018;3:14

[26] Kanduc D.From hepatitis C virus immunoproteomics to rheumatology via cross-reactivity in one table. Curr Opin Rheumatol 2019;31(05):488-492

[27] Kanduc D.Immunobiology: on the inexistence of a negative selection process. Adv Stud Biol 2020;12:19-28

[28] Kanduc D.Hydrophobicity and the physico-chemical basis of immunotolerance. Pathobiology 2020;87(04):268-276

[29] Kanduc D, Shoenfeld Y.Molecular mimicry between SARS-CoV-2 spike glycoprotein and mammalian proteomes: implications for the vaccine. Immunol Res 2020;68(05):310-313

[30] Kanduc D, Shoenfeld Y.Medical, genomic, and evolutionary aspects of the peptide sharing between pathogens, primates, and humans. Glob Med Genet 2020;7(02):64-67

[31] Abee CR, Keeling ME, Mansfield K, Tardif S, Morris T. Nonhuman Primates in Biomedical Research. Vol. 2: Diseases Academic Press, ElsevierOxford, UK2012

[32] Pasetti MF, Resendiz-Albor A, Ramirez K, et al.Heterologous prime-boost strategy to immunize very young infants against measles: pre-clinical studies in rhesus macaques. Clin Pharmacol Ther 2007;82(06):672-685

[33] Verstrepen BE, Oostermeijer H, Fagrouch Z, et al.Vaccine-induced protection of rhesus macaques against plasma viremia after intradermal infection with a European lineage 1 strain of West Nile virus. PLoS One 2014;9(11):e112568

[34] Stephenson KE, Wegmann F, Tomaka F, et al.Comparison of shortened mosaic HIV-1 vaccine schedules: a randomised, double- blind, placebo-controlled phase 1 trial (IPCAVD010/ HPX1002) and a preclinical study in rhesus monkeys (NHP 17- 22). Lancet HIV 2020;7(06):e410-e421

[35] van Doremalen N, Lambe T, Spencer A, et al. ChAdOx1 nCoV-19 vaccine prevents SARS-CoV-2 pneumonia in rhesus macaques. Nature 2020;586(7830):578-582

[36] Lu S, Zhao Y, Yu W, et al.Comparison of nonhuman primates identified the suitable model for COVID-19. Signal Transduct Target Ther 2020;5(01):157

[37] Sun W, Singh AK.Plague vaccine: recent progress and prospects. npjVaccines 2019 (e-pub ahead of print). Doi: 10.1038/s41541-019-0105-9

[38] Shedlock DJ, Silvestri G, Weiner DB.Monkeying around with HIV vaccines: using rhesus macaques to define ‘gatekeepers’ for clinical trials. Nat Rev Immunol 2009;9(10):717-728

[39] UniProt Consortium. UniProt: a worldwide hub of protein knowledge. Nucleic Acids Res 2019;47(D1):D506-D515

[40] Chen C, Li Z, Huang H, Suzek BE, Wu CH, UniProt Consortium. A fast Peptide Match service for UniProt Knowledgebase. Bioinformatics 2013;29(21):2808-2809

[41] Morgat A, Lombardot T, Coudert E, et al; UniProt Consortium. Enzyme annotation in UniProtKB using Rhea. Bioinformatics 2020;36(06):1896-1901

[42] Varki A.A chimpanzee genome project is a biomedical imperative. Genome Res 2000;10(08):1065-1070

[43] Olson MV, Varki A.Sequencing the chimpanzee genome: insights into humanevolutionanddisease.NatRevGenet 2003;4(01):20-28

[44] Varki A, Altheide TK.Comparing the human and chimpanzee genomes: searching for needles in a haystack. Genome Res 2005; 15(12):1746-1758

[45] Lucchese G, Stufano A, Calabro M, Kanduc D. Charting the peptide crossreactome between HIV-1 and the human proteome. Front Biosci (Elite Ed) 2011;3:1385-1400

[46] Barouch DH, Tomaka FL, Wegmann F, et al.Evaluation of a mosaic HIV-1 vaccine in a multicentre, randomised, doubleblind, placebo-controlled, phase 1/2a clinical trial (APPROACH) and in rhesus monkeys (NHP 13-19). Lancet 2018;392(10143):232-243

[47] Thomas C.Roadblocks in HIV research: five questions. Nat Med 2009;15(08):855-859

[48] Cohen J. Another HIV vaccine strategy fails in large-scale study. Science 2020 (e-pub ahead of print). Doi: 10.1126/science.abb1480

[49] Sabin AB.Oral poliovirus vaccine: history of its development and use and current challenge to eliminate poliomyelitis from the world. J Infect Dis 1985;151(03):420-436

[50] Lerner A, Jeremias P, Matthias T.The world incidence and prevalence of autoimmune diseases is increasing. Int J Celiac Dis 2015; 3:151-155

[51] Bond KA, Franklin LJ, Sutton B, Firestone SM.Q-Vax Q fever vaccine failures, Victoria, Australia 1994-2013. Vaccine 2017;35(51):7084-7087

[52] Breakwell L, Moturi E, Helgenberger L, et al.Measles outbreak associated with vaccine failure in adults-Federated States of Micronesia, February-August 2014. MMWR Morb Mortal Wkly Rep 2015;64(38):1088-1092

[53] Cherry JD.Epidemic pertussis and acellular pertussis vaccine failure in the 21st century. Pediatrics 2015;135(06): 1130-1132

[54] Lopez-Lacort M, Collado S, Díez-Gandía A, Díez-Domingo J.Rotavirus, vaccine failure or diagnostic error? Vaccine 2016;34(48): 5912-5915

[55] Mahalingam S, Herring BL, Halstead SB.Call to action for dengue vaccine failure. Emerg Infect Dis 2013;19(08):1335-1337

[56] Moinho R, Brett A, Ferreira G, Lemos S.Pneumococcal vaccine failure: can it be a primary immunodeficiency? BMJ Case Rep 2014;2014:bcr2014204714

[57] Naylor C, Lu M, Haque R, et al; PROVIDE study teams. Environmental enteropathy, oral vaccine failure and growth faltering in infants in Bangladesh. EBioMedicine 2015;2(11): 1759-1766

[58] Poland GA.Influenza vaccine failure: failure to protect or failure to understand? Expert Rev Vaccines 2018;17(06):495-502

[59] Ramsay M, Brown K.The public health implications of secondary measles vaccine failure. J Prim Health Care 2013; 5(02):92

[60] Wiedermann U, Garner-Spitzer E, Wagner A.Primary vaccine failure to routine vaccines: why and what to do? Hum Vaccin Immunother 2016;12(01):239-243

[61] Pieczenik G.Are the universes of antibodies and antigens symmetrical? Reprod Biomed Online 2003;6(02):154-156

[62] Kanduc D.Pentapeptides as minimal functional units in cell biology and immunology. Curr Protein Pept Sci 2013;14(02): 111-120

[63] Puente XS, Gutiérrez-Fernández A, Ordóñez GR,Hillier LW, López- Otín C.Comparative genomic analysis of human and chimpanzee proteases. Genomics 2005;86(06):638-647

[64] Glazko G, Veeramachaneni V, Nei M, Makałowski W.Eighty percent of proteins are different between humans and chimpanzees. Gene 2005;346:215-219

[65] Sharp AJ, Locke DP, McGrath SD, et al. Segmental duplications and copy-number variation in the human genome. Am J Hum Genet 2005;77(01):78-88

[66] Hahn MW, Demuth JP, Han SG.Accelerated rate of gene gain and loss in primates. Genetics 2007;177(03):1941-1949

[67] Dumas L, Kim YH, Karimpour-Fard A, et al. Gene copy number variation spanning 60 million years of human and primate evolution. Genome Res 2007;17(09):1266-1277

[68] Marques-Bonet T, Kidd JM, Ventura M, et al.A burst of segmental duplications in the genome of the African great ape ancestor. Nature 2009;457(7231):877-881

[69] Blekhman R, Oshlack A, Gilad Y.Segmental duplications contribute to gene expression differences between humans and chimpanzees. Genetics 2009;182(02):627-630

[70] Kapopoulou A, Mathew L,Wong A, Trono D, Jensen JD. The evolution of gene expression and binding specificity of the largest transcription factor family in primates. Evolution 2016;70(01):167-180

[71] Hamilton AT, Huntley S, Tran-Gyamfi M, Baggott DM, Gordon L, Stubbs L.Evolutionary expansion and divergence in the ZNF91 subfamily of primate-specific zinc finger genes. Genome Res 2006;16(05):584-594

[72] Khaitovich P, Hellmann I, Enard W, et al.Parallel patterns of evolution in the genomes and transcriptomes of humans and chimpanzees. Science 2005;309(5742):1850-1854

[73] Enard W, Khaitovich P, Klose J, et al.Intra- and interspecific variation in primate gene expression patterns. Science 2002; 296(5566):340-343

[74] Kanduc D.“Self-nonself” peptides in the design of vaccines. Curr Pharm Des 2009;15(28):3283-3289

[75] Kanduc D.The self/nonself issue: a confrontation between proteomes. Self Nonself 2010;1(03):255-258

[76] Lucchese G, Stufano A, Kanduc D.Proposing low-similarity peptide vaccines againstMycobacterium tuberculosis. J Biomed Biotechnol 2010;2010:832341

[77] Angelini G, Bonamonte D, Lucchese A, et al.Preliminary data on Pemphigus vulgaris treatment by a proteomics-defined peptide: a case report. J Transl Med 2006;4:43

[78] Kanduc D.Immunogenicity, immunopathogenicity, and immunotolerance in one graph. Anticancer Agents Med Chem 2015;15(10): 1264-1268

RIGHTS & PERMISSIONS

2021 Global Medical Genetics