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

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 (HAd...

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Main Authors: Nahid Omidi, Azarakhsh Azaran, Manoochehr Makvandi, Gholamreza Khataminia, Kambiz Ahmadi Angali, Shahram Jalilian
Format: Article
Language:English
Published: Tehran University of Medical Sciences 2022-10-01
Series:Iranian Journal of Microbiology
Subjects:
Online Access:https://ijm.tums.ac.ir/index.php/ijm/article/view/3419
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author Nahid Omidi
Azarakhsh Azaran
Manoochehr Makvandi
Gholamreza Khataminia
Kambiz Ahmadi Angali
Shahram Jalilian
author_facet Nahid Omidi
Azarakhsh Azaran
Manoochehr Makvandi
Gholamreza Khataminia
Kambiz Ahmadi Angali
Shahram Jalilian
author_sort Nahid Omidi
collection DOAJ
description 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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spelling doaj.art-559a89f436764f81857269b5a2163acd2022-12-22T03:25:59ZengTehran University of Medical SciencesIranian Journal of Microbiology2008-32892008-44472022-10-01145Characterization 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 approachNahid Omidi0Azarakhsh Azaran1Manoochehr Makvandi2Gholamreza Khataminia3Kambiz Ahmadi Angali4Shahram Jalilian5Infectious and Tropical Diseases Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IranInfectious and Tropical Diseases Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IranInfectious and Tropical Diseases Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IranDepartment of Ophthalmology, Infectious Ophthalmologic Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IranDepartment of Biostatistics and Epidemiology Division, Health School, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IranInfectious and Tropical Diseases Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran 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. https://ijm.tums.ac.ir/index.php/ijm/article/view/3419In silico model;Adenovirus E1A proteins;Keratoconjunctivitis;Molecular docking;Cytotoxic T-lymphocyte
spellingShingle Nahid Omidi
Azarakhsh Azaran
Manoochehr Makvandi
Gholamreza Khataminia
Kambiz Ahmadi Angali
Shahram Jalilian
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
Iranian Journal of Microbiology
In silico model;
Adenovirus E1A proteins;
Keratoconjunctivitis;
Molecular docking;
Cytotoxic T-lymphocyte
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic In silico model;
Adenovirus E1A proteins;
Keratoconjunctivitis;
Molecular docking;
Cytotoxic T-lymphocyte
url https://ijm.tums.ac.ir/index.php/ijm/article/view/3419
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