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.
Adenovirus E1A proteins
Cytotoxic T-lymphocyte
In silico model
Keratoconjunctivitis
Molecular docking
Journal
Iranian journal of microbiology
ISSN: 2008-3289
Titre abrégé: Iran J Microbiol
Pays: Iran
ID NLM: 101518404
Informations de publication
Date de publication:
Oct 2022
Oct 2022
Historique:
entrez:
19
12
2022
pubmed:
20
12
2022
medline:
20
12
2022
Statut:
ppublish
Résumé
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. 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. 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. Combined with 3D protein modeling, this study predicted the epitopes of E1A CR2 protein in HAdVs.
Sections du résumé
Background and Objectives
UNASSIGNED
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
UNASSIGNED
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
UNASSIGNED
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
UNASSIGNED
Combined with 3D protein modeling, this study predicted the epitopes of E1A CR2 protein in HAdVs.
Identifiants
pubmed: 36531810
doi: 10.18502/ijm.v14i5.10971
pii: IJM-14-746
pmc: PMC9723420
doi:
Types de publication
Journal Article
Langues
eng
Pagination
746-758Informations de copyright
Copyright © 2022 The Authors. Published by Tehran University of Medical Sciences.
Références
Infect Genet Evol. 2021 Jan;87:104648
pubmed: 33264668
Int Ophthalmol. 2021 Jun;41(6):2149-2156
pubmed: 33730316
PeerJ. 2019 Jan 14;6:e6185
pubmed: 30656066
Clin Ophthalmol. 2020 Mar 17;14:837-852
pubmed: 32256043
J Immunother Cancer. 2019 Jul 10;7(1):174
pubmed: 31291991
J Virol. 2014 Sep;88(18):10894-908
pubmed: 25008941
BMC Infect Dis. 2018 Mar 20;18(1):135
pubmed: 29558885
Sci Rep. 2019 Mar 13;9(1):4409
pubmed: 30867498
J Immunol. 2020 Jan 1;204(1):87-100
pubmed: 31776205
PLoS One. 2013 Apr 22;8(4):e59592
pubmed: 23630567
J Virol. 2004 Apr;78(8):3897-905
pubmed: 15047806
J Med Virol. 2021 Aug;93(8):4840-4845
pubmed: 33543795
Int J Ophthalmol. 2019 Sep 18;12(9):1420-1425
pubmed: 31544037
J Biomed Sci. 2017 Nov 23;24(1):88
pubmed: 29169357
J Immunol. 2001 Sep 1;167(5):2522-8
pubmed: 11509591
FEBS Lett. 2019 Dec;593(24):3484-3495
pubmed: 31721176
Ophthalmology. 2018 Sep;125(9):1344-1353
pubmed: 29602567
Oncotarget. 2016 Jul 26;7(30):48309-48320
pubmed: 27340782
Eur J Pediatr. 2008 Jun;167(6):633-40
pubmed: 17876605
Comput Biol Chem. 2017 Oct;70:156-163
pubmed: 28886485
DNA Repair (Amst). 2019 Feb;74:80-90
pubmed: 30583959
Proteomics. 2017 Jan;17(1-2):
pubmed: 27928884
Virology. 2018 Dec;525:117-131
pubmed: 30265888
Future Virol. 2012 Nov 1;7(11):1077-1088
pubmed: 23630544
Biomed J. 2016 Dec;39(6):382-390
pubmed: 28043417
Clin Microbiol Rev. 2014 Jul;27(3):441-62
pubmed: 24982316
Iran Biomed J. ;22(2):134-7
pubmed: 28952291
Nat Protoc. 2017 Feb;12(2):255-278
pubmed: 28079879
Semin Respir Crit Care Med. 2016 Aug;37(4):586-602
pubmed: 27486739
Infect Genet Evol. 2017 Apr;49:309-317
pubmed: 28185986
Viruses. 2018 Nov 22;10(12):
pubmed: 30469473
J Immunol. 2019 Jan 15;202(2):618-624
pubmed: 30530481
West J Emerg Med. 2017 Apr;18(3):509-517
pubmed: 28435504