In silico CD4+ T cell epitope mapping and HLA coverage analysis for proteins of human hepatitis E virus

Abstract

Hepatitis E virus (HEV) infection is a common cause of sporadic and epidemic viral hepatitis in developing countries, and is being increasingly recognized in many developed countries. The genome of HEV consists of three overlapping open reading frames that code for viral structural and non-structural proteins. Data on T helper cells epitopes in HEV proteins are limited. We therefore used NetMHCIIpan web server for in silico prediction of peptide sequence that may act as promiscuous helper T lymphocyte epitopes. This was followed by HLA coverage analysis using the population coverage tool of Immune Epitope Database to calculate the fraction of individuals in various populations who may be expected to respond to sets of such peptides based on the HLA genotypic frequencies. Three 9-mer peptide cores in the HEV capsid protein were predicted to be putative binders to several HLA-DR alleles. In silico data suggest that these three peptide cores may together be expected to act as T-cell epitopes in more than 80% of persons in 9 of the 12 populations studied. Each of these three peptide sequences was found to be fully conserved over 35 full length HEV genome sequences belonging to all four known HEV genotypes. It may be useful to validate the role of peptides containing these three core peptide sequences as T-cell epitopes in in vitro or in vivo experiments. If confirmed as T-cell epitopes in such studies, these peptides could be useful adjucts to the HEV recombinant vaccines, currently under development either as additives or in a prime-boost approach.