Original Article
 

Hepatitis C Virus Subtype 3a Envelope Protein 1 Binding with Human Leukocyte Antigen Class I Types of Pakistani Population: Candidate Epitopes for Synthetic Peptide Vaccine

Abstract

The object of this cross sectional study was to determine the HCV subtype 3a envelope protein binding affinity with Human Leukocyte Antigen. Envelope 1 (E1) protein is one of the structural proteins responsible for entering the cells through the receptors. The binding affinity of E1 protein epitopes to the selected Human Leukocyte Antigen (HLA) class I alleles was investigated using the computer-based tools. These prediction tools were also used to design the synthetic vaccine’s candidate epitopes and to identify the individuals/populations who are likely to be responder to those vaccines.The mean frequency of HLA I antigens in Pakistani population was calculated. Three alleles each from HLA A and B were selected. E1 protein sequence extracted from HCV 3a isolates was retrieved and twenty-four sequences of it were selected. NetMHCcons 1.0 server was used to determine the binding affinities of HLA alleles to the epitope sequences of 10 amino acids in length.A02, A03, A11, A24, A33, B08, B13, B15, B35 and B40 were the first five antigens more prevalent in Pakistan each from HLA A and HLA B.. We did not find any binding affinity between HLA A*201, B*1501 and B*4001 and epitopes from E1 sequences in a threshold of 50 nM. Totally five various epitopes derived from different isolates were characterized.The prediction of HLA-E1 epitope specific bindings and the forthcoming response can be a useful bioinformatics tool to uncover the right synthetic peptides for vaccine design purposes.

1. Ur Rehman I, Vaughan G, Purdy MA, Xia GL, Forbi JC, Rossi LM, et al. Genetic history of hepatitis C virus in Pakisan. Infect Genet Evol 2014; 318:24.

2. Saleha S, Kamal A, Ullah F, Khan N, Mahmood A, Khan S. Prevalence of hepatitis C virus genotypes in district Bannu, Khyber Pakhtunkhwa, Pakistan. Hepat Res Treat 2014; 2014:165826.

3. Rehman I, Idress M, Ali M, Ali L, Butt S, Hussain, A et al. Hepatitis C virus genotype 3a with phylogenetically distinct origin is circulating in Pakistan. Genet Vaccines Ther 2011; 9(1):2.

4. Afzal S, Idrees M, Ali M, Ilyas M, Hussain A, Akram M, et al. Envelope 2 protein phosphorylation sites S75 and 277 of hepatitis C genotype 1a and interferon resistance: A sequence alignment approach. Virol J 2011; 8:71.

5. Ahfaq UA, Javed T, Rehman S, Nawaz Z, Riazuddin S.An overview of HCV molecular biology, replication and immune responses. Virol J 2011; 8:161.

6. Frey SE, Houghton M, Coates S, Abrignani S, Chien D, Rosa D, et al. Safety and immunogenicity of HCV E1E2 vaccine adjuvanated with MF59 administered to healthy adults. Vaccine 2010; 28(38):6367-73.

7. Law LMJ, Landi A, Magee WC, Tyrrell DL, Houghton M. Progress towards a hepatitis C virus vaccine. Emerging microbes and infections 2013; 2: e79.

8. Meunier JC, Gottwein JM, Houghton M, Russell RS, Emerson SU, Bukh J, et al. Vaccine induced cross genotype reactive neutralizing antibodies against hepatitis C virus. J Infect Dis 2011; 204(8):1186-90.

9. Stamataki Z, Coates S, Abrignani S, Houghton M, McKeating JA. Immunization of human volunteers with hepatitis C virus envelope glycoproteins elicits antibodies that cross neutralize heterologous virus strains. J Infect Dis 2011; 204(5):811-3.

10. HLA Nomenclature: HLA Alleles Numbers. [cited 2014, August 25] Available from: http://hla.alleles.org/nomenclature/stats.html.

11. Tipu HN, Ahmed D. Differential binding of Aspergillus fumigatus allergenic proteins to human leukocyte antigen (HLA) alleles in dry lab: potential for immunotherapy. Cell Biol: Res Ther 2014; 3:1.

12. Hillen N, Mesteri G, Lemmel C, Weinzierl AO, Muller M, Wernet D, et al. Essential Differences in Ligand Presentation and T Cell Epitope Recognition among HLA Molecules of the HLA B44 Supertypes. Eur J Immunol 2008; 38(11):2993-3003.

13. Shehzadi A, Shakoori FR, Shakoori AR.Immunoinformatics study of promiscuous HLA binding antigenic nanomers of surface glycoproteins of Influenza A (H1N1) pdm09 of Asian origin. Pakistan J Zool 2013;45(3): 733-40.

14. Whelan FJ, Yap NVL, Surette MG, Golding GB, Bowdish DM. A Guide to Bioinformatics for Immunologists. Front Immunol 2013; 4:416.

15. Sirskyj D, Diaz-Mitoma F, Golshani A, Kumar A, Azizi A. Innovative Bioinformatic Approaches for Developing Peptide-based Vaccines Against Hypervariable Viruses. Immunol Cell Biol 2011; 89(1):81-9.

16. Allele frequencies in worldwide populations [online] [cited 2014, August 22] Available from: http://www.allelefrequencies.net/hla6006a.asp 17. Thomsen M, Lundegaard C, Buus S, Rasmussen M, Lund O, Nielsen M. MHCcluster, a method for functional clustering of MHC molecules. Immunogenetics 2013;65(9):655-65.

18. Karosiene E, Lundegaard C, Lund O, Nielsen M.NetMHCcons: a consensus method for the major histocompatibility complex class I predictions. Immunogenetics 2012; 64(3):177-86.

19. Attaullah S, Khan S, Ali I. Hepatitis C virus genotypes in Pakistan: A systemic review. Virol J 2011; 8:433.

20. Groot DSA, Sbai H, Aubin SC, Mcmurry J, Martin W.Immuno-informatics: Mining genomes for vaccine development. Immunol Cell Biol 2002; 80(30):255-69.

21. Shehzadi A, Ur Rehman S, Idrees M. Promiscuous prediction and conservancy analysis of CTL binding epitopes of HCV 3a viral proteome from Punjab Pakistan:an In Silico Approach. Virol J 2011; 8:55.

22. Ikram A, Anjum S, Tahir M. In silico identification and conservation analysis of B-cell and T-cell epitopes of hepatitis C virus 3a genotype enveloped glycoprotein 2 from Pakistan: A step towards heterologous vaccine design. Hepat Mon 2014; 14(6):e9832.

23. Idrees S, Ashfaq UA. Structural analysis and epitope prediction of HCV E1 protein isolated in Pakistan: an in- silico approach. Virol J 2013; 10:113.

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IssueVol 14, No 5 (2015) QRcode
SectionOriginal Article(s)
Keywords
Bioinformatics Hepatitis C virus envelope 1 (E1) protein Human Leukocyte Antigen

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How to Cite
1.
Nawaz-Tipu H. Hepatitis C Virus Subtype 3a Envelope Protein 1 Binding with Human Leukocyte Antigen Class I Types of Pakistani Population: Candidate Epitopes for Synthetic Peptide Vaccine. Iran J Allergy Asthma Immunol. 2015;14(5):526-534.