Evaluation of potential MHC-I allele-specific epitopes in Zika virus proteins and the effects of mutations on peptide-MHC-I interaction studied using in silico approaches. (June 2021)

• Record Type: Journal Article
• Authors: da Costa, Aline Silva; Fernandes, Tácio Vinício Amorim; Bello, Murilo Lamim; de Souza, Theo Luiz Ferraz
• Is Part Of: Computational biology and chemistry. Volume 92(2021)
• Publication Date: 2021-06
• Subjects: ADE antibody-dependent enhancement -- ANN artificial neural network -- CAPRI critical assessment of prediction of interactions -- C capsid protein -- CTL CD8 + T cells -- DENV dengue virus -- E envelope protein -- EMM gas-phase energy -- GB generalized Born -- Gsol solvation free energy -- HLA human leukocyte antigen -- IEDB Immune Epitope Database and Analysis Resource -- LCPO Linear Combination of Pairwise Overlaps -- MD molecular dynamics -- MM/GBSA molecular mechanics/generalized Born surface area -- MHC-I major histocompatibility complex class I -- NPT isothermal and isobaric ensemble -- PDB Protein Data Bank -- PHEIC Public Health Emergency of International Concern -- pMHC-I peptide-MHC-I -- PRODIGY PROtein binDIng enerGY -- PME Particle mesh Ewald -- prM/M pre-membrane/membrane protein -- PSSMs Position Specific Scoring Matrices -- HADDOCK High Ambiguity Driven protein-protein DOCKing -- RMSD root-mean-square deviation -- RMSF root-mean-square Fluctuation -- SASA solvent-accessible surface area -- TAP transporter associated with antigen processing -- TCR T-cell receptor -- WHO World Health Organization -- YFV yellow fever virus -- ZIKV Zika virus; Zika virus -- Epitope prediction -- Protein mutation -- Immunoinformatics -- Molecular docking -- Molecular dynamics simulation; Chemistry -- Data processing -- Periodicals; Biology -- Data processing -- Periodicals; Biochemistry -- Data processing; Biology -- Data processing; Molecular biology -- Data processing; Periodicals; Electronic journals; 542.85
• DOI: 10.1016/j.compbiolchem.2021.107459
• Languages: English
• ISSNs: 1476-9271

Abstract

Graphical abstract: Highlights: Potential epitopes are HLA allele specific. Lys45 in B pock et of HLA B44 leads to selective binding of peptides with Glu at P2. Asp at P1 of epitopes decrease the HLA B8 binding affinity and stability. Mutation from Thr to Pro at P2 of the NS5 832 decrease the HLA A1 binding affinity. The immunodominant peptide E 4 in mice has low HLA B 44 binding affinity. Abstract: Zika virus (ZIKV) infection is a global health concern due to its association with microcephaly and neurological complications. The development of a T-cell vaccine is important to combat this disease. In this study, we propose ZIKV major histocompatibility complex I (MHC-I) epitopes based on in silico screening consensus followed by molecular docking, PRODIGY, and molecular dynamics (MD) simulation analyses. The effects of the reported mutations on peptide-MHC-I (pMHC-I) complexes were also evaluated. In general, our data indicate an allele-specific peptide-binding human leukocyte antigen (HLA) and potential epitopes. For HLA-B44, we showed that the absence of acidic residue Glu at P2, due to the loss of the electrostatic interaction with Lys45, has a negative impact on the pMHC-I complex stability and explains the low free energy estimated for the immunodominant peptide E-4 (IGVSNRDFV). Our MD data also suggest the deleterious effects of acidic residue Asp at P1 on the pMHC-I stability of HLA-B8 due to destabilization of the α-helix and β-strand. Free energy estimation further indicated that the mutation from Val to Ala at P9 of peptide E-247 (DAHAKRQTV), which was found exclusively in microcephaly samples, did not reduce HLA-B8 affinity. In contrast, the mutation from Thr to Pro at P2 of the peptide NS5−832 (VTKWTDIPY) decreased the interaction energy, number of intermolecular interactions, and adversely affected its binding mode with HLA-A1. Overall, our findings are important with regard to the design of T-cell peptide vaccines and for understanding how ZIKV escapes recognition by CD8 + T-cells.