Characterization of the conserved regions of E1A protein from human adenovirus for reinforcement of cytotoxic T lymphocytes responses to the all genogroups causes ocular manifestation through an in silico approach
-
Nahid Omidi
,
Azarakhsh Azaran
,
Manoochehr Makvandi
,
Gholamreza Khataminia
,
Kambiz Ahmadi Angali
,
Shahram Jalilian
Abstract
Background and Objectives: Adenovirus species B, C, D, and E are the most common causes of ocular manifestations caused by adenoviruses. FDA-approved treatment agents for adenovirus infections are not available. Cell-mediated immunity is the major protective mechanism versus human adenoviruses (HAdVs) infection and T cells specific for peptide epitopes from nonstructural proteins can prevent adenoviral dissemination. E1A CR2 region of HAdVs Epitopes predicted for reinforcing cytotoxic T lymphocytes (CTLs) in the EKC patients. Among human adenoviruses E1 protein, four distinct E1A regions had a significantly higher level of homology than the rest of E1A protein. E1A protein inhibits IFN signal transduction. Epitope-based vaccines are designed to have flexible and simple methods to synthesize a vaccine, using an adjuvant to trigger fast immune responses. CTL epitopes were applied to create a multiepitope vaccine. Conserve region1 (CR1) and CR3 have less antigenicity compared to CR2. Additionally, CR3 in HAdV-D8 contains three toxic areas. CR4 similar to the two regions CR1 and CR3 do not show acceptable antigenic properties.
Materials and Methods: Bioinformatics’ tools were used to predict, refine and validate the 3D structure of the construct. Effective binding was predicted by protein-protein docking of the epitope vaccine with MHC-I molecules and revealed the safety and efficacy of the predicted vaccine construct.
Results: In silico analysis show that rising levels of cytotoxic CD8 + T cells, TH1 cells, macrophages, and neutrophils are linked to IFN-dominant TH1-type responses, which are detected in putative immune individuals.
Conclusion: Combined with 3D protein modeling, this study predicted the epitopes of E1A CR2 protein in HAdVs.
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26. Zhang A, Tessier TM, Galpin KJC, King CR, Gameiro SF, Anderson WW, et al. The transcriptional repressor BS69 is a conserved target of the E1A proteins from several human adenovirus species. Viruses 2018; 10: 662.
27. Schumacher FR, Delamarre L, Jhunjhunwala S, Modrusan Z, Phung QT, Elias JE, et al. Building proteomic tool boxes to monitor MHC class I and class II peptides. Proteomics 2017; 17: 10.1002/pmic.201600061.
28. Hadadianpour A, Samiee Aref MH, Zeinali S. High-Resolution HLA-A Typing in Normal Iranian Population. Iran Biomed J 2018; 22: 134-137.
29. Meza B, Ascencio F, Sierra-Beltrán AP, Torres J, Angulo C. A novel design of a multi-antigenic, multistage and multi-epitope vaccine against Helicobacter pylori: An in silico approach. Infect Genet Evol 2017; 49: 309-317.
30. Lei Y, Zhao F, Shao J, Li Y, Li S, Chang H, et al. Application of built-in adjuvants for epitope-based vaccines. PeerJ 2019; 6: e6185.
31. Tourani M, Karkhah A, Najafi A. Development of an epitope-based vaccine inhibiting immune cells rolling and migration against atherosclerosis using in silico approaches. Comput Biol Chem 2017; 70: 156-163.
32. Shey RA, Ghogomu SM, Esoh KK, Nebangwa ND, Shintouo CM, Nongley NF, et al. In-silico design of a multi-epitope vaccine candidate against onchocerciasis and related filarial diseases. Sci Rep 2019; 9: 4409.
33. Kozakov D, Hall DR, Xia B, Porter KA, Padhorny D, Yueh C, et al. The ClusPro web server for protein–protein docking. Nat Protoc 2017; 12: 255-278.
34. Den Boer AT, Diehl L, Van Mierlo GJ, Van Der Voort EI, Fransen MF, Krimpenfort P, et al. Longevity of antigen presentation and activation status of APC are decisive factors in the balance between CTL immunity versus tolerance. J Immunol 2001; 167: 2522-2528.
35. Altan-Yaycioglu R, Sahinoglu-Keskek N, Canan H, Coban-Karatas M, Ulas B. Effect of diluted povidone iodine in adenoviral keratoconjunctivitis on the rate of subepithelial corneal infiltrates. Int J Ophthalmol 2019; 12: 1420-1425.
2. Patwary NIA, Islam MS, Sohel M, Ara I, Sikder MOF, Shahik SM. In silico structure analysis and epitope prediction of E3 CR1-beta protein of Human Adenovirus E for vaccine design. Biomed J 2016; 39: 382-390.
3. Lynch JP 3rd, Kajon AE. Adenovirus: epidemiology, global spread of novel serotypes, and advances in treatment and prevention. Semin Respir Crit Care Med 2016; 37: 586-602.
4. Li J, Lu X, Jiang B, Du Y, Yang Y, Qian H, et al. Adenovirus-associated acute conjunctivitis in Beijing, China, 2011–2013. BMC Infect Dis 2018; 18: 135.
5. Labib BA, Minhas BK, Chigbu DI. Management of adenoviral keratoconjunctivitis: challenges and solutions. Clin Ophthalmol 2020; 14: 837-852.
6. Yıldırım Y, Akbaş YB, Tunç U, Yıldız BK, Er MO, Demirok A. Visual rehabilitation by using corneal wavefront-guided transepithelial photorefractive keratectomy for corneal opacities after epidemic keratoconjunctivitis. Int Ophthalmol 2021; 41: 2149-2156.
7. Miro E, Del Cuerpo M, Rubio M, Berengua C, Español M, Marin P, et al. Whole‐genome analysis to describe a human adenovirus D8 conjunctivitis outbreak in a tertiary hospital. J Med Virol 2021; 93: 4840-4845.
8. Lion T. Adenovirus infections in immunocompetent and immunocompromised patients. Clin Microbiol Rev 2014; 27: 441-462.
9. Lamarche BJ, Orazio NI, Goben B, Meisenhelder J, You Z, Weitzman MD, et al. Repair of protein-linked DNA double strand breaks: Using the adenovirus genome as a model substrate in cell-based assays. DNA Repair (Amst) 2019; 74: 80-90.
10. Sohn S-Y, Hearing P. Adenoviral strategies to overcome innate cellular responses to infection. FEBS Lett 2019; 593: 3484-3495.
11. Fang L, Cheng Q, Zhao J, Ge Y, Zhu Q, Zhao M, et al. A p53-independent apoptotic mechanism of adenoviral mutant E1A was involved in its selective antitumor activity for human cancer. Oncotarget 2016; 7: 48309-48320.
12. Glavina J, Román EA, Espada R, De Prat-Gay G, Chemes LB, Sánchez IE. Interplay between sequence, structure and linear motifs in the adenovirus E1A hub protein. Virology 2018; 525: 117-131.
13. Lopes A, Feola S, Ligot S, Fusciello M, Vandermeulen G, Préat V, et al. Oncolytic adenovirus drives specific immune response generated by a poly-epitope pDNA vaccine encoding melanoma neoantigens into the tumor site. J Immunother Cancer 2019; 7: 174.
14. Dos Santos Franco L, Oliveira Vidal P, Amorim JH. In silico design of a Zika virus non-structural protein 5 aiming vaccine protection against zika and dengue in different human populations. J Biomed Sci 2017; 24: 88.
15. Testa JS, Philip R. Role of T-cell epitope-based vaccine in prophylactic and therapeutic applications. Future Virol 2012; 7: 1077-1088.
16. Cheng C-C, Huang L-M, Kao C-L, Lee P-I, Chen J-M, Lu C-Y, et al. Molecular and clinical characteristics of adenoviral infections in Taiwanese children in 2004–2005. Eur J Pediatr 2008; 167: 633-640.
17. Gilani CJ, Yang A, Yonkers M, Boysen-Osborn M. Differentiating urgent and emergent causes of acute red eye for the emergency physician. West J Emerg Med 2017; 18: 509-517.
18. Pihos AM. Epidemic keratoconjunctivitis: a review of current concepts in management. J Optom 2013; 6: 69-74.
19. Sohn SY, Hearing P. Adenoviral strategies to overcome innate cellular responses to infection. FEBS Lett 2019; 593: 3484-3495.
20. Lee CS, Lee AY, Akileswaran L, Stroman D, Najafi-Tagol K, Kleiboeker S, et al. Determinants of outcomes of adenoviral keratoconjunctivitis. Ophthalmology 2018; 125: 1344-1353.
21. Jackson SE, Mason GM, Okecha G, Sissons JGP, Wills MR. Diverse specificities, phenotypes, and antiviral activities of cytomegalovirus-specific CD8+ T cells. J Virol 2014; 88: 10894-10908.
22. Keib A, Mei Y-F, Cicin-Sain L, Busch DH, Dennehy KM. Measuring antiviral capacity of T cell responses to adenovirus. J Immunol 2019; 202: 618-624.
23. Enders M, Franken L, Philipp M-S, Kessler N, Baumgart A-K, Eichler M, et al. Splenic Red Pulp Macrophages Cross-Prime Early Effector CTL That Provide Rapid Defense against Viral Infections. J Immunol 2020; 204: 87-100.
24. Jain N, Shankar U, Majee P, Kumar A. Scrutinizing the SARS-CoV-2 protein information for the designing an effective vaccine encompassing both the T-cell and B-cell epitopes. Infect Genet Evol 2021; 87: 104648.
25. Geyeregger R, Freimüller C, Stevanovic S, Stemberger J, Mester G, Dmytrus J, et al. Short-term in-vitro expansion improves monitoring and allows affordable generation of virus-specific T-cells against several viruses for a broad clinical application. PLoS One 2013; 8(4): e59592.
26. Zhang A, Tessier TM, Galpin KJC, King CR, Gameiro SF, Anderson WW, et al. The transcriptional repressor BS69 is a conserved target of the E1A proteins from several human adenovirus species. Viruses 2018; 10: 662.
27. Schumacher FR, Delamarre L, Jhunjhunwala S, Modrusan Z, Phung QT, Elias JE, et al. Building proteomic tool boxes to monitor MHC class I and class II peptides. Proteomics 2017; 17: 10.1002/pmic.201600061.
28. Hadadianpour A, Samiee Aref MH, Zeinali S. High-Resolution HLA-A Typing in Normal Iranian Population. Iran Biomed J 2018; 22: 134-137.
29. Meza B, Ascencio F, Sierra-Beltrán AP, Torres J, Angulo C. A novel design of a multi-antigenic, multistage and multi-epitope vaccine against Helicobacter pylori: An in silico approach. Infect Genet Evol 2017; 49: 309-317.
30. Lei Y, Zhao F, Shao J, Li Y, Li S, Chang H, et al. Application of built-in adjuvants for epitope-based vaccines. PeerJ 2019; 6: e6185.
31. Tourani M, Karkhah A, Najafi A. Development of an epitope-based vaccine inhibiting immune cells rolling and migration against atherosclerosis using in silico approaches. Comput Biol Chem 2017; 70: 156-163.
32. Shey RA, Ghogomu SM, Esoh KK, Nebangwa ND, Shintouo CM, Nongley NF, et al. In-silico design of a multi-epitope vaccine candidate against onchocerciasis and related filarial diseases. Sci Rep 2019; 9: 4409.
33. Kozakov D, Hall DR, Xia B, Porter KA, Padhorny D, Yueh C, et al. The ClusPro web server for protein–protein docking. Nat Protoc 2017; 12: 255-278.
34. Den Boer AT, Diehl L, Van Mierlo GJ, Van Der Voort EI, Fransen MF, Krimpenfort P, et al. Longevity of antigen presentation and activation status of APC are decisive factors in the balance between CTL immunity versus tolerance. J Immunol 2001; 167: 2522-2528.
35. Altan-Yaycioglu R, Sahinoglu-Keskek N, Canan H, Coban-Karatas M, Ulas B. Effect of diluted povidone iodine in adenoviral keratoconjunctivitis on the rate of subepithelial corneal infiltrates. Int J Ophthalmol 2019; 12: 1420-1425.
| Files | ||
| Issue | Vol 14 No 5 (2022) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijm.v14i5.10971 | |
| Keywords | ||
| In silico model; Adenovirus E1A proteins; Keratoconjunctivitis; Molecular docking; Cytotoxic T-lymphocyte | ||
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Omidi N, Azaran A, Makvandi M, Khataminia G, Ahmadi Angali K, Jalilian S. Characterization of the conserved regions of E1A protein from human adenovirus for reinforcement of cytotoxic T lymphocytes responses to the all genogroups causes ocular manifestation through an in silico approach. Iran J Microbiol. 2022;14(5):746-758.
