Predicting and Designing Epitope Ensemble Vaccines against HTLV-1.

Saruar Alam,Omar Hamza Bin Manjur,Akib Mahmud Khan,Mahmud Arif Pavel,Md Faruk Hossain,Md Kamrul Hasan,Zinat Sharmin

doi:10.1515/jib-2018-0051

Abstract

The infection mechanism and pathogenicity of Human T-lymphotropic virus 1 (HTLV-1) are ambiguously known for hundreds of years. Our knowledge about this virus is recently emerging. The purpose of the study is to design a vaccine targeting the envelope glycoprotein, GP62, an outer membrane protein of HTLV-1 that has an increased number of epitope binding sites. Data collection, clustering and multiple sequence alignment of HTLV-1 glycoprotein B, variability analysis of envelope Glycoprotein GP62 of HTLV-1, population protection coverage, HLA-epitope binding prediction, and B-cell epitope prediction were performed to predict an effective vaccine. Among all the predicted peptides, ALQTGITLV and VPSSSTPL epitopes interact with three MHC alleles. The summative population protection coverage worldwide by these epitopes as vaccine candidates was found nearly 70%. The docking analysis revealed that ALQTGITLV and VPSSSTPL epitopes interact strongly with the epitope-binding groove of HLA-A*02:03, and HLA-B*35:01, respectively, as this HLA molecule was found common with which every predicted epitope interacts. Molecular dynamics simulations of the docked complexes show they form stable complexes. So, these potential epitopes might pave the way for vaccine development against HTLV-1.

Highlights

Human T-lymphotropic virus 1 (HTLV-1) is a positive single-stranded RNA virus belongs to the Retroviridae family and Delta retrovirus genus
Retrovirus inserted into the host genome is referred to as provirus [2]. mRNA of HTLV-1 encodes different functionally crucial proteins including the gag, pol, and env genes present in other exogenous retroviruses, and several regulatory genes at the 3’ end of the genome whose products regulate the expression, splicing, and transport of the viral mRNAs
Envelope Glycoprotein GP62 of HTLV-1 was targeted to design the vaccine because glycoproteins are located on the outer layer of the cell membrane and can be recognized by the immune system

Summary

Introduction

HTLV-1 is a positive single-stranded RNA virus belongs to the Retroviridae family and Delta retrovirus genus. The total genome size of HTLV-1 is 8507 nucleotides in length encoding 6 different proteins. In one stage of the HTLV-1 lifecycle, the RNA is utilized to synthesize double-stranded DNA which inserted into the genomic DNA of a host cell [1]. MRNA of HTLV-1 encodes different functionally crucial proteins including the gag, pol, and env genes present in other exogenous retroviruses, and several regulatory genes at the 3’ end of the genome whose products regulate the expression, splicing, and transport of the viral mRNAs. The pol gene encodes three enzyme functions: polymerase, protease, and integrase [3], [4], [5], [6], [7]. HTLV-1 remains the causal agent of severe diseases that can be subdivided into three different criteria’s: Neoplasia (T cell lymphoma in adult Cutaneous, T cell leukemia), inflammatory syndromes (Uveitis, Arthropathy, HAM/TSP, Sjogren’s syndrome, T lymphocyte alveolitis, Polymyositis, Pneumopathy), and Infectious complications (Tuberculosis, Leprosy, Strongyloides stercoralis) [4], [17], [18], [19], [20], [21]

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