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

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 im- munity is the major protective mechanism versus humanadenoviruses (HAdVs) infection and T cells specific for peptide epitopes from nonstructural proteins can prevent adenoviral dissemination. E1A CR2 regionof HAdVs Epitopes predicted for reinforcing cytotoxic T lymphocytes (CTLs) in the EKC patients. Among human adenoviruses E1 protein, four distinct E1Aregions had a significantly higher level of homology than the rest of E1A protein. E1A protein inhibits IFN signal trans- duction. Epitope-based vaccines aredesigned to have flexible and simple methods to synthesize a vaccine, using an adjuvant to trigger fast immune responses. CTL epitopes were applied to create amultiepitope 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 byprotein-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.

Application of oncolytic virus in tumor therapy

“…Infection with oncolytic adenovirus initiates the expression of the E1A gene, which is a key gene for adenovirus replication. 62 Many promoters that can specifically initiate E1A expression in tumor cells have been applied to improve the specific antitumor activity of OAd, including the human telomerase reverse transcriptase promoter, hypoxia-responsive promoter, prostatespecific antigen promoter, ɑ-fetoprotein promoter, ɑ-lactalbumin promoter, and MUCin1 promoter (DF3/MUC1). [63][64][65] 4.2 | Enhance the body's immune response…”