Degree Type

Dissertation

Date of Award

2007

Degree Name

Doctor of Philosophy

Department

Theses & dissertations (Interdisciplinary)

Major

Bioinformatics and Computational Biology

First Advisor

Drena Dobbs

Second Advisor

Kai-Ming Ho

Abstract

Macromolecular interactions are essential for virtually all cellular functions including signal transduction processes, metabolic processes, regulation of gene expression and immune responses. This dissertation focuses on the characterization of two important macromolecular interactions involved in the relationship between Equine Infectious Anemia Virus (EIAV) and its host cell in horse: (i) the interaction between the EIAV Rev protein and its binding site, the Rev-responsive element (RRE) and (ii) interactions between equine MHC class I molecules and epitope peptides derived from EIAV proteins.;EIAV, one of the most divergent members of the lentivirus family, has a single-stranded RNA genome and carries several regulatory and structural proteins within its viral particle. Rev is an essential EIAV regulatory encoded protein that interacts with the viral RRE, a specific binding site in the viral mRNA. Using a combination of experimental and computational methods, the interactions between EIAV Rev and RRE were characterized in detail. EIAV Rev was shown to have a bipartite RNA binding domain containing two arginine rich motifs (ARMs). The RRE secondary structure was determined and specific structural motifs that act as cis-regulatory elements for EIAV Rev-RRE interaction were identified. Interestingly, a structural motif located in the high affinity Rev binding site is well conserved in several diverse lentiviral genomes, including HIV-1.;Macromolecular interactions involved in the immune response of the horse to EIAV infection were investigated by analyzing complexes between MHC class I proteins and epitope peptides derived from EIAV Rev, Env and Gag proteins. Computational modeling results provided a mechanistic explanation for the experimental finding that a single amino acid change in the peptide binding domain of the equine MHC class I molecule differentially affects the recognition of specific epitopes by EIAV-specific CTL. Together, the findings in this dissertation provide novel insights into the strategy used by EIAV to replicate itself, and provide new details about how the host cell responds to and defends against EIAV upon the infection. Moreover, they have contributed to our understanding of the macromolecular recognition events that regulate these processes.

DOI

https://doi.org/10.31274/rtd-180813-16780

Publisher

Digital Repository @ Iowa State University, http://lib.dr.iastate.edu/

Copyright Owner

Jae-Hyung Lee

Language

en

Proquest ID

AAI3289365

OCLC Number

213331961

ISBN

9780549334804

File Format

application/pdf

File Size

206 pages

Share

COinS