Predicting immune response targets in orthoflaviviruses through sequence homology and computational analysis.

Autor: Are VN; Department of Biosciences and Biomedical Engineering, Indian Institute of Technology, Indore, 453552, MP, India.; Department of Biological Sciences, Purdue University, West Lafayette, IN, 47907, USA., Roy R; Department of Biosciences and Biomedical Engineering, Indian Institute of Technology, Indore, 453552, MP, India.; Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN, 47907, USA., Dhanda SK; Division of Neuro-Oncology, Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA., Neema S; Department of Biosciences and Biomedical Engineering, Indian Institute of Technology, Indore, 453552, MP, India., Sahu NR; Department of Biological Sciences, Indian Institute of Science Education and Research Bhopal, Bhopal, 462066, MP, India., Adithya N; Department of Biological Sciences, Indian Institute of Science Education and Research Bhopal, Bhopal, 462066, MP, India., Tiwari R; Department of Biosciences and Biomedical Engineering, Indian Institute of Technology, Indore, 453552, MP, India.; Department of Medicine, Washington University in St. Louis, St. Louis, MO, 63130, USA., Kar P; Department of Biosciences and Biomedical Engineering, Indian Institute of Technology, Indore, 453552, MP, India., Nayak D; Department of Biological Sciences, Indian Institute of Science Education and Research Bhopal, Bhopal, 462066, MP, India. debasis@iiserb.ac.in.
Jazyk: angličtina
Zdroj: Journal of molecular modeling [J Mol Model] 2024 Jul 31; Vol. 30 (8), pp. 295. Date of Electronic Publication: 2024 Jul 31.
DOI: 10.1007/s00894-024-06088-8
Abstrakt: Context: Flaviviruses cause severe encephalitic or hemorrhagic diseases in humans. Its members, Kyasanur forest disease virus (KFDV) and Alkhumra hemorrhagic fever virus (ALKV), cause hemorrhagic fever and are prevalent in India and Saudi Arabia, respectively, while the tick-borne encephalitis virus (TBEV) causes a dangerous encephalitic infection in Europe and Asia. However, little information is available about the targets of immune responses for these deadly viruses. Here, we predict potential antigenic peptide epitopes of viral envelope protein for inducing a cell-mediated and humoral immune response.
Methods: Using the Immune Epitope Database and Analysis Resource (IEDB-AR), we identified 13 MHC-I and two MHC-II dominant conserved epitopes in KFDV and ALKV and six MHC-I and three MHC-II epitopes in TBEV envelope proteins. Parallelly, we also predicted B-cell linear and discontinuous envelope protein epitopes for these viruses. Interestingly, the epitopes are conserved in all three viral envelope proteins. Further, the discontinuous epitopes are structurally compared with the available DENV, ZIKV, WNV, TBEV, and LIV envelope protein antibody structures. Overall structural comparison analyses highlight (i) lateral ridge epitope in the ED-III domain of E protein, and (ii) envelope dimer epitope (EDE) could be targeted for developing potent vaccine candidates as well as therapeutic antibody production. Moreover, existing structural and biochemical functions of the same epitopes in homologous viruses are predicted to have a reduced antibody-dependent enhancement (ADE) effect on flaviviral infection.
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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