Sequence analysis of hepatitis C virus nonstructural protein 3-4A serine protease and prediction of conserved B and T cell epitopes.

The hepatitis C virus (HCV) is a global health issue. The nonstructural protein 3 (NS3)-4Agene of HCV is responsible for serine protease activity. The aim of the present study was to develop a global consensus sequence of HCV serine protease, analyze conserved residues, and predict highly conserved B- and T-cell binding epitopes in the NS3-4A protein. A total of 160 NS3-4A sequences from the six genotypes of HCV were refracted in the current study. The amino acid sequences were aligned to obtain a global consensus sequence. The location of possible B- and T-cell epitopes were predicted in the HCV NS3-4A consensus sequence by employing bioinformatics tools. Despite the high mutation rate of HCV, the functionally important residues are highly conserved. These include residues that form the catalytic triad (His57, Asp81 and Ser139), the S1 and S6 pocket, zinc-binding site (Cys97, Cys99, Cys145 and His149) and the substrate binding groove. The epitopes B1, B8 and B9 are predicted to be ideal candidates for B-cell-based vaccine and are >95% conserved across six major HCV genotypes. The major histocompatibility complex (MHC) class I epitopes, M4, M5, M7 and M10, and MHC class II epitopes, T5, T7 and T10 are ideal epitopes for vaccine development with high antigenicity scores and high conservancy across major HCV genotypes. The predicted B- and T-cell epitopes are ideal targets for vaccine development, and are capable of producing a strong immune response for all major genotypes of HCV.