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Host-pathogen interactions and evolution of epitopes in HIV-1: understanding selection and escape

Paul, Sinu
http://rave.ohiolink.edu/etdc/view?acc_num=kent1334509644

Abstract Details

2012, PHD, Kent State University, College of Arts and Sciences / Department of Biological Sciences.
Epitopes, the specific regions encoded by pathogens’ genomes that are recognized by the host immune receptors, play an important role in host-pathogen interaction and in turn, in determining the progression of the disease. While some of the mutations in epitope regions make the immune system unable to recognize epitopes and thus result in escape from the host immune response, other mutations may significantly reduce the viral fitness. This study explores the patterns of molecular evolution across different epitope regions and identifies a set of highly conserved epitopes in the Human Immunodeficiency Virus-1 (HIV-1) genome in an attempt to discover epitope vaccine candidates. To delineate the extent of selection pressure driven by interactions with the immune system at different CTL, T-Helper and Antibody epitope regions, the levels of sequence identity of 603 HIV-1 epitopes were examined in HIV-1, HIV-2 and SIV reference genomes. Despite rather high degree of sequence variability of the HIV-1 genome, several epitopes in Gag and Pol genes were identified as comparatively more conserved than those elsewhere in the genome. The results also showed that CTL epitopes were much more conserved compared to T-helper and antibody epitopes. Using data mining technique association rule mining, it was shown that some of these highly conserved CTL and T-helper epitopes co-occurred in various HIV-1 genomes irrespective of subtype, recombination status or geographical location suggesting co-evolution and association between these epitopes. These highly conserved and co-evolving epitopes should be considered as potent candidates for a multi-epitope vaccine and/or promising drug targets against HIV-1. In addition, several computational tools were developed to facilitate the analysis of epitope sequences and the extensive information on the sequence identity of all the HIV-1 epitopes were collated in a database. This novel strategy in identifying co-evolving epitopes and the detailed information on HIV-1 epitope conservation can further aid in the design of an efficient vaccine.
Helen Piontkivska, PhD (Advisor)
Christopher Woolverton, PhD (Committee Member)
Walter Hoeh, PhD (Committee Member)
Ruoming Jin, PhD (Committee Member)
Quan Li, PhD (Committee Member)
216 p.
Bioinformatics; Biology; Evolution and Development
Epitopes; HIV-1; Vaccine candidates; Association rule mining; Epitope analysis tools; Epitope database; Data mining; Bioinformatics; Molecular Evolution

Recommended Citations

Citations

  • Paul, S. (2012). Host-pathogen interactions and evolution of epitopes in HIV-1: understanding selection and escape [Doctoral dissertation, Kent State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=kent1334509644

    APA Style (7th edition)

  • Paul, Sinu. Host-pathogen interactions and evolution of epitopes in HIV-1: understanding selection and escape. 2012. Kent State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=kent1334509644.

    MLA Style (8th edition)

  • Paul, Sinu. "Host-pathogen interactions and evolution of epitopes in HIV-1: understanding selection and escape." Doctoral dissertation, Kent State University, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=kent1334509644

    Chicago Manual of Style (17th edition)

kent1334509644
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© 2012, all rights reserved.
This open access ETD is published by Kent State University and OhioLINK.