West Nile virus–associated HLA-DRB1 alleles in the Greek population: A structural perspective

Abstract

The HLA system plays a significant role via the regulation of the immune system and contributes to the progression and protection of many diseases. In our previous study, several HLA-DRB1 alleles were found to have a susceptible or protective role toward infection and neuroinvasion of West Nile Virus (WNV) in the Greek population. As expected, the majority of polymorphic positions are located in the peptide-binding region of the molecule. In the present work, the structure of these alleles was studied in silico, to examine the effect of polymorphism on the conformation of DRB1 proteins, with the aspect of WNV association. More specifically, molecular dynamics simulations were used for structural prediction of 23 available alleles. These modeled alleles were evaluated using root-mean-square deviation (RMSD) and root-mean-square fluctuation analysis. Low RMSD values indicate that different alleles have similar structures. Furthermore, low fluctuation was observed in the peptide-binding region between alleles with the higher and the lowest RMSD values. These findings indicate that probably variable residues do not affect the behavior of DRB1 alleles in WNV disease, by causing structural differences between them.