CC BY 4.0 · Glob Med Genet 2021; 08(04): 176-182
DOI: 10.1055/s-0041-1735590
Original Article

From Anti-Severe Acute Respiratory Syndrome Coronavirus 2 Immune Response to Cancer Onset via Molecular Mimicry and Cross-Reactivity

1   Department of Biosciences, Biotechnologies, and Biopharmaceutics, University of Bari, Bari, Italy
› Author Affiliations
Funding None.

Abstract

Background and Objectives Whether exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may predispose to the risk of cancer in individuals with no prior cancers is a crucial question that remains unclear. To confirm/refute possible relationships between exposure to the virus and ex novo insurgence of tumors, this study analyzed molecular mimicry and the related cross-reactive potential between SARS-CoV-2 spike glycoprotein (gp) antigen and human tumor-suppressor proteins.

Materials and Methods Tumor-associated proteins were retrieved from UniProt database and analyzed for pentapeptide sharing with SARS-CoV-2 spike gp by using publicly available databases.

Results An impressively high level of molecular mimicry exists between SARS-CoV-2 spike gp and tumor-associated proteins. Numerically, 294 tumor-suppressor proteins share 308 pentapeptides with the viral antigen. Crucially, the shared peptides have a relevant immunologic potential by repeatedly occurring in experimentally validated epitopes. Such immunologic potential is of further relevancy in that most of the shared peptides are also present in infectious pathogens to which, in general, human population has already been exposed, thus indicating the possibility of immunologic imprint phenomena.

Conclusion This article described a vast peptide overlap between SARS-CoV-2 spike gp and tumor-suppressor proteins, and supports autoimmune cross-reactivity as a potential mechanism underlying prospective cancer insurgence following exposure to SARS-CoV-2. Clinically, the findings call for close surveillance of tumor sequelae that possibly could result from the current coronavirus pandemic.

Supplementary Material



Publication History

Received: 16 July 2021

Accepted: 02 August 2021

Article published online:
07 September 2021

© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Huang C, Wang Y, Li X. et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395 (10223): 497-506
  • 2 Sadeghzadeh-Bazargan A, Rezai M, Najar Nobari N, Mozafarpoor S, Goodarzi A. Skin manifestations as potential symptoms of diffuse vascular injury in critical COVID-19 patients. J Cutan Pathol 2021; DOI: 10.1111/cup.14059.
  • 3 Boechat JL, Chora I, Morais A, Delgado L. The immune response to SARS-CoV-2 and COVID-19 immunopathology - current perspectives. Pulmonology 2021; 27 (05) 423-437
  • 4 Cabrera Martimbianco AL, Pacheco RL, Bagattini ÂM, Riera R. Frequency, signs and symptoms, and criteria adopted for long COVID-19: s systematic review. Int J Clin Pract 2021; e14357
  • 5 Rosen HR, O'Connell C, Nadim MK. et al. Extrapulmonary manifestations of severe acute respiratory syndrome coronavirus-2 infection. J Med Virol 2021; 93 (05) 2645-2653
  • 6 Ramos-Casals M, Brito-Zerón P, Mariette X. Systemic and organ-specific immune-related manifestations of COVID-19. Nat Rev Rheumatol 2021; 17 (06) 315-332
  • 7 Suárez-Reyes A, Villegas-Valverde CA. Implications of low-grade inflammation in SARS-CoV-2 immunopathology. MEDICC Rev 2021; 23 (02) 42
  • 8 Han HJ, Nwagwu C, Anyim O, Ekweremadu C, Kim S. COVID-19 and cancer: from basic mechanisms to vaccine development using nanotechnology. Int Immunopharmacol 2021; 90: 107247
  • 9 Corti C, Curigliano G. Commentary: SARS-CoV-2 vaccines and cancer patients. Ann Oncol 2021; 32 (04) 569-571
  • 10 Xia P, Dubrovska A. Tumor markers as an entry for SARS-CoV-2 infection?. FEBS J 2020; 287 (17) 3677-3680
  • 11 Chakravarty D, Ratnani P, Sobotka S. et al. Increased hospitalization and mortality from COVID-19 in prostate cancer patients. Cancers (Basel) 2021; 13 (07) 1630
  • 12 Vanni G, Pellicciaro M, Materazzo M. et al. Advanced stages and increased need for adjuvant treatments in breast cancer patients: the effect of the one-year COVID-19 pandemic. Anticancer Res 2021; 41 (05) 2689-2696
  • 13 Park JY, Lee YJ, Kim T. et al. Collateral effects of the coronavirus disease 2019 pandemic on lung cancer diagnosis in Korea. BMC Cancer 2020; 20 (01) 1040
  • 14 Taylor R, Omakobia E, Sood S, Glore RJ. The impact of coronavirus disease 2019 on head and neck cancer services: a UK tertiary centre study. J Laryngol Otol 2020; 134 (08) 684-687
  • 15 Derosa L, Melenotte C, Griscelli F. et al. The immuno-oncological challenge of COVID-19. Nat Can 2020; 1: 946-964
  • 16 Natale C, Giannini T, Lucchese A, Kanduc D. Computer-assisted analysis of molecular mimicry between human papillomavirus 16 E7 oncoprotein and human protein sequences. Immunol Cell Biol 2000; 78 (06) 580-585
  • 17 Kanduc D, Stufano A, Lucchese G, Kusalik A. Massive peptide sharing between viral and human proteomes. Peptides 2008; 29 (10) 1755-1766
  • 18 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
  • 19 Kanduc D. Peptide cross-reactivity: the original sin of vaccines. Front Biosci (Schol Ed) 2012; 4: 1393-1401
  • 20 Lucchese G, Kanduc D. Potential crossreactivity of human immune responses against HCMV glycoprotein B. Curr Drug Discov Technol 2016; 13 (01) 16-24
  • 21 Lucchese G, Kanduc D. Zika virus and autoimmunity: from microcephaly to Guillain-Barré syndrome, and beyond. Autoimmun Rev 2016; 15 (08) 801-808
  • 22 Kanduc D. From anti-SARS-CoV-2 immune responses to COVID-19 via molecular mimicry. Antibodies (Basel) 2020; 9 (03) 33
  • 23 Kanduc D. Pentapeptides as minimal functional units in cell biology and immunology. Curr Protein Pept Sci 2013; 14 (02) 111-120
  • 24 Kanduc D. Homology, similarity, and identity in peptide epitope immunodefinition. J Pept Sci 2012; 18 (08) 487-494
  • 25 UniProt Consortium. UniProt: a worldwide hub of protein knowledge. Nucleic Acids Res 2019; 47 (D1): D506-D515
  • 26 Vita R, Mahajan S, Overton JA. et al. The Immune Epitope Database (IEDB): 2018 update. Nucleic Acids Res 2019; 47 (D1): D339-D343
  • 27 Gutierrez A, Kentsis A, Sanda T. et al. The BCL11B tumor suppressor is mutated across the major molecular subtypes of T-cell acute lymphoblastic leukemia. Blood 2011; 118 (15) 4169-4173
  • 28 Bartram I, Gökbuget N, Schlee C. et al. Low expression of T-cell transcription factor BCL11b predicts inferior survival in adult standard risk T-cell acute lymphoblastic leukemia patients. J Hematol Oncol 2014; 7: 51
  • 29 Yang P, Kollmeyer TM, Buckner K, Bamlet W, Ballman KV, Jenkins RB. Polymorphisms in GLTSCR1 and ERCC2 are associated with the development of oligodendrogliomas. Cancer 2005; 103 (11) 2363-2372
  • 30 Clark SL, Rodriguez AM, Snyder RR, Hankins GD, Boehning D. Structure-function of the tumor suppressor BRCA1. Comput Struct Biotechnol J 2012; 1 (01) e201204005
  • 31 Angeli D, Salvi S, Tedaldi G. Genetic predisposition to breast and ovarian cancers: how many and which genes to test?. Int J Mol Sci 2020; 21 (03) 1128
  • 32 Rai R, Sharma KL, Tiwari S, Misra S, Kumar A, Mittal B. DCC (deleted in colorectal carcinoma) gene variants confer increased susceptibility to gallbladder cancer (Ref. No.: Gene-D-12-01446). Gene 2013; 518 (02) 303-309
  • 33 Ellis CA, Vos MD, Howell H, Vallecorsa T, Fults DW, Clark GJ. Rig is a novel Ras-related protein and potential neural tumor suppressor. Proc Natl Acad Sci U S A 2002; 99 (15) 9876-9881
  • 34 Duncan G, McCormick C, Tufaro F. The link between heparan sulfate and hereditary bone disease: finding a function for the EXT family of putative tumor suppressor proteins. J Clin Invest 2001; 108 (04) 511-516
  • 35 Huang EY, Madireddi MT, Gopalkrishnan RV. et al. Genomic structure, chromosomal localization and expression profile of a novel melanoma differentiation associated (mda-7) gene with cancer specific growth suppressing and apoptosis inducing properties. Oncogene 2001; 20 (48) 7051-7063
  • 36 Allen M, Pratscher B, Roka F. et al. Loss of novel mda-7 splice variant (mda-7s) expression is associated with metastatic melanoma. J Invest Dermatol 2004; 123 (03) 583-588
  • 37 Hisaoka M, Tanaka A, Hashimoto H. Molecular alterations of h-warts/LATS1 tumor suppressor in human soft tissue sarcoma. Lab Invest 2002; 82 (10) 1427-1435
  • 38 Murakami H, Mizuno T, Taniguchi T. et al. LATS2 is a tumor suppressor gene of malignant mesothelioma. Cancer Res 2011; 71 (03) 873-883
  • 39 Di Benedetto M, Pineau P, Nouet S. et al. Mutation analysis of the 8p22 candidate tumor suppressor gene ATIP/MTUS1 in hepatocellular carcinoma. Mol Cell Endocrinol 2006; 252 (1-2): 207-215
  • 40 Liang Y, Zhang C, Dai DQ. Identification of DNA methylation-regulated differentially-expressed genes and related pathways using Illumina 450K BeadChip and bioinformatic analysis in gastric cancer. Pathol Res Pract 2019; 215 (10) 152570
  • 41 Nazarenko I, Schäfer R, Sers C. Mechanisms of the HRSL3 tumor suppressor function in ovarian carcinoma cells. J Cell Sci 2007; 120 (Pt 8): 1393-1404
  • 42 Oh JJ, Razfar A, Delgado I. et al. 3p21.3 tumor suppressor gene H37/Luca15/RBM5 inhibits growth of human lung cancer cells through cell cycle arrest and apoptosis. Cancer Res 2006; 66 (07) 3419-3427
  • 43 Brandt DT, Baarlink C, Kitzing TM. et al. SCAI acts as a suppressor of cancer cell invasion through the transcriptional control of beta1-integrin. Nat Cell Biol 2009; 11 (05) 557-568
  • 44 Ramakrishna S, Suresh B, Bae SM, Ahn WS, Lim KH, Baek KH. Hyaluronan binding motifs of USP17 and SDS3 exhibit anti-tumor activity. PLoS One 2012; 7 (05) e37772
  • 45 Iacobas DA, Mgbemena VE, Iacobas S, Menezes KM, Wang H, Saganti PB. Genomic fabric remodeling in metastatic clear cell renal cell carcinoma (ccRCC): a new paradigm and proposal for a personalized gene therapy approach. Cancers (Basel) 2020; 12 (12) 3678
  • 46 van Everdink WJ, Baranova A, Lummen C. et al. RFP2, c13ORF1, and FAM10A4 are the most likely tumor suppressor gene candidates for B-cell chronic lymphocytic leukemia. Cancer Genet Cytogenet 2003; 146 (01) 48-57
  • 47 Xu L, Wu Q, Zhou X, Wu Q, Fang M. TRIM13 inhibited cell proliferation and induced cell apoptosis by regulating NF-κB pathway in non-small-cell lung carcinoma cells. Gene 2019; 715: 144015
  • 48 Francis T, Salk JE, Quilligan JJ. Experience with vaccination against influenza in the spring of 1947: a preliminary report. Am J Public Health Nations Health 1947; 37 (08) 1013-1016
  • 49 Davenport FM, Hennessy AV, Francis Jr T. Epidemiologic and immunologic significance of age distribution of antibody to antigenic variants of influenza virus. J Exp Med 1953; 98 (06) 641-656
  • 50 Lucchese G, Kanduc D. The Guillain–Barrè peptide signatures: from Zika virus to Campylobacter, and beyond. Virus Adaptation and Treatment 2017; 9: 1-11
  • 51 Lucchese G, Kanduc D. Minimal immune determinants connect Zika virus, human cytomegalovirus, and Toxoplasma gondii to microcephaly-related human proteins. Am J Reprod Immunol 2017; 77 (02) e12608
  • 52 Kanduc D. Immunobiology: on the inexistence of a negative selection process. Adv Stud Biol 2020; 12 (01) 19-28
  • 53 Kanduc D. Anti-SARS-CoV-2 Immune response and sudden death: titin as a link. Adv Stud Biol 2021; 13 (01) 37-44
  • 54 Kanduc D, Shoenfeld Y. Inter-pathogen peptide sharing and the original antigenic sin: solving a paradox. Open Immunol J 2018; 8: 16-27
  • 55 Kanduc D. Thromboses and hemostasis disorders associated with coronavirus disease 2019: the possible causal role of cross-reactivity and immunological imprinting. Glob Med Genet 2021; DOI: 10.1055/s-0041-1731068.
  • 56 Trost B, Lucchese G, Stufano A, Bickis M, Kusalik A, Kanduc D. No human protein is exempt from bacterial motifs, not even one. Self Nonself 2010; 1 (04) 328-334
  • 57 Kanduc D. The comparative biochemistry of viruses and humans: an evolutionary path towards autoimmunity. Biol Chem 2019; 400 (05) 629-638
  • 58 Europe's Beating Cancer Plan: A new EU approach to prevention, treatment and care. [Internet] Accessed on May 2021 at: https://ec.europa.eu/commission/presscorner/detail/en/ip_21_342