Abstract
Human immunodeficiency virus (HIV) possesses a major threat to the human life largely due to the unavailability of an efficacious vaccine and poor access to the antiretroviral drugs against this deadly virus. High mutation rate in the viral genome underlying the antigenic variability of the viral proteome is the major hindrance as far as the antibody based vaccine development is concerned. Although the exact mechanism by which CTL epitopes and the restricting HLA alleles mediate their action towards slow disease progression is still not clear, the important CTL restricted epitopes for controlling viral infections can be utilized in future vaccine design. This study was designed for the characterization the HIV-1 optimal CTL epitopes and their corresponding HLA alleles. CTL epitope cluster distribution analysis revealed only two HIV-1 proteins, namely, Nef and Gag, which have significant cluster forming capacity. We have found the role of specific HLA supertypes such as HLA B∗07, HLA B∗58, and HLA A∗03 in selecting the hydrophobic and conserved amino acid positions within Nef and Gag proteins, to be presented as epitopes. The analyses revealed that the clusters of optimal epitopes for Nef and p24 proteins of HIV-1 could potentially serve as a source of vaccine.
Highlights
Human immunodeficiency virus (HIV), a retrovirus that belongs to the Lentiviridae family, is the causative agent of acquired immunodeficiency syndrome (AIDS)
One significant achievement in computational immunology is the method of identification of immunoproteasome cleavage sites within the query proteins by using different algorithms such as artificial neural network (ANN) which enables the rapid identification of a wide range of potential epitopes that can be analyzed both computationally and experimentally for their affinity to bind with particular human leukocyte antigen (HLA) class I molecules
As CTL response against HIV infected cells is proved to be crucial in controlling virus population in the host, rationally the CTL based vaccine should have a profound effect on HIV infection
Summary
Human immunodeficiency virus (HIV), a retrovirus that belongs to the Lentiviridae family, is the causative agent of acquired immunodeficiency syndrome (AIDS). In this devastating situation of world AIDS epidemic, there is an urgent need of developing effective HIV vaccine as no vaccine is proved to be efficacious to control HIV infection To combat this deadly virus, its genome, proteome, pathogenesis, and mechanisms of evasion of immune response should be studied in great detail. Goulder and Watkins have suggested three additional lines of evidence which signifies the potential role of CTLs in suppressing HIV infection: first they argued that specific HLA class I molecules are consistently associated with particular HIV disease outcomes They highlighted the fact that more rapid disease progression is observed in individuals with HLA class I homozygosity, and lastly they provided evidence that the loss of immune control over HIV infection arises when viral mutants escape CD8+ T-cell recognition [13]. All the above mentioned evidence signifies the important antagonizing role of CTL immune response in HIV disease progression
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