Amino Acid Substitutions Created in Reverse Transcriptase and their Influence on Hiv-1 Mutation Frequencies
Katherine Excoffon (Committee Member), Heather Hostetler (Committee Member), Dawn P. Wooley (Advisor)
Master of Science (MS)
As research has shown, a high mutation rate occurs during the reverse transcription RT process because HIV reverse transcriptase fails to correct erroneously incorporated nucleotides during the reverse transcription process. Based on various research articles, a series of amino acid substitutions created in RT were collected to find out their influence on virus mutation frequencies. Two tables were used; one for amino acid substitutions created in RT that increased the HIV-1 mutation rate and another for amino acid substitutions created in RT that decreased the HIV-1 mutation rate. The tables show which amino acid substitutions created in RT decreased or increased the mutation rate of HIV-1. With more amino acid substitutions showing a decrease in the mutation rate of HIV-1, the tables provide researchers with helpful information for future research. Additionally, the information resulted in three new findings. First, When viewing single amino acids identified with drug resistance, most showed a decrease in the frequency of the mutation rate the of HIV-1; however, if the specified amino acid is not identified with drug resistance most showed an increase in the HIV-1 mutation rate. Second, when HIV-1 has an increased mutation rate multiple amino acids showed drug resistance. Finally, a structural rationale for the location of residues implicated in the resistance of nucleoside-analog inhibitors (Huang et al., 1998) showed that mutations that decrease and/or increase the mutation rate do not cluster together. Those specified mutations are all around the active site in the crystal structure. Also, these amino acids might be in the primer grip region or interact with the incoming dNTP, and form the dNTP binding site or residues in the fingers subdomain.
Department or Program
Microbiology and Immunology
Year Degree Awarded
Copyright 2011, all rights reserved. This open access ETD is published by Wright State University and OhioLINK.