In silico analysis of MHC-I restricted epitopes of Chikungunya virus proteins: Implication in underst-ing anti-CHIKV CD8(+) T cell response and advancement of epitope based immunotherapy for CHIKV infection

Autor(es): Pratheek B M, Suryawanshi Amol R, Chattopadhyay Soma, Chattopadhyay Subhasis


Resumo: Chikungunya virus (CHIKV) is a mosquito-borne Alphavirus, responsible for acute febrile infection. The high morbidity - socio-economic loss associated with the recent CHIKV epidemics worldwide have raised a great public health concern - emphasize the need to study the immunological basis of CHIKV infection to control the disease. MHC-I restricted CD8(+) T cell response represent one of the major anti-viral immune responses. Accordingly, it is essential to have a detailed underst-ing towards CHIKV specific MHC-I restricted immunogenic epitopes for anti-viral CD8(+) CTL immunogenicity. In the present study, a computational approach was used to predict the conserved MHC-I epitopes for mouse haplotypes (H2-Db - H2-Dd) - some alleles of the major HLA-I supertypes (HLA-A2, -A3, -A24, -B7, -B15) of all CHIKV proteins. Further, an in-depth computational analysis was carried out to validate the selected epitopes for their nature of conservation in different global CHIKV isolates to assess their binding affinities to the appropriate site of respective MHC-I molecules - to predict anti-CHIKV CD8(+) CTL immunogenicity. Our analyses resulted in fifteen highly conserved epitopes for H2-Db - H2-Dd - fifty epitopes for different HLA-I supertypes. Out of these, the MHC-I epitopes VLLPNVHTL - MTPERVTRL were found to have highest predictable CTL immunogenicities - least binding energies for H2-Db - H2-Dd, whereas, for HLA-I, the epitope FLTLFVNTL was with the highest population coverage, CTL immunogenicity - least binding energy. Hence, our study has identified MHC-I restricted epitopes that may help in the advancement of MHC-I restricted epitope based anti-CHIKV immune responses against this infection - this will be useful towards the development of epitope based anti-CHIKV immunotherapy in the future. However, further experimental investigations for cross validation - evaluation are warranted to establish the ability of epitopes to induce CD8(+) T cell mediated immune responses.


Palavras-Chave: Chikungunya virus; H2-Db; H2-Dd; HLA-I; MHC-I epitope


Imprenta: Infection, Genetics and Evolution, v. 31, p. 118-126, 2015


Identificador do objeto digital: 10.1016/j.meegid.2015.01.017


Descritores: Chikungunya virus - Cell ; Chikungunya virus - Genome ; Chikungunya virus - Immune response ; Chikungunya virus - Molecular structure ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Proteins ; Chikungunya virus - Immune response ; Chikungunya virus - T lymphocytes ; Chikungunya virus - Viral infections ; Chikungunya virus - Molecular methods ; Chikungunya Virus - Virus ; Chikungunya virus - Chikungunya fever ; Chikungunya virus - Epidemic ; Chikungunya virus - Immunology ; Chikungunya virus - Public health


Data de publicação: 2015