Date of Award
Fall 12-2023
Degree Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
School
Mathematics and Natural Sciences
Committee Chair
Jacques Kessl
Committee Chair School
Mathematics and Natural Sciences
Committee Member 2
Fengwei Bai
Committee Member 2 School
Biological, Environmental, and Earth Sciences
Committee Member 3
Matthew Donahue
Committee Member 3 School
Mathematics and Natural Sciences
Committee Member 4
Faqing Huang
Committee Member 4 School
Mathematics and Natural Sciences
Committee Member 5
Vijay Rangachari
Committee Member 5 School
Mathematics and Natural Sciences
Abstract
HIV-1 integrase (IN) is an essential enzyme for the viral life cycle as it integrates viral genomic material into the host cell genome. In addition to its’ essential catalytic function, IN has another important non-catalytic role where it binds the viral RNA to facilitate successful particle maturation during the viral life cycle. A significant number of IN mutants, addressed as class II IN mutants, show various defects, affecting different steps of the viral life cycle. Class II IN mutants exhibit aberrant morphology where viral ribonucleoprotein particles are mislocalized outside of the capsid core. This phenomenon can be observed in the presence of allosteric integrase inhibitors (ALLINIs) as well. Recent studies showed the aberrant morphology associated with the Class II IN mutants is achieved due to the loss of interaction between the IN and vRNA. Therefore, understanding the interaction between the IN and the viral RNA is important to reveal the molecular mechanisms underlying the maturation process. In our study, we have investigated this interaction through mass spectrometry based methods. Our analysis showed the important amino acid residues that take part in the IN-vRNA interaction that we have detailed in this work. Overall, these findings reveal additional information regarding the underlying mechanism of the essential non-catalytic activity of HIV-1 IN.
Recommended Citation
Catmakas, Tolga, "STRUCTURAL FEATURES OF HIV-1 INTEGRASE IN THE LATE STAGE OF VIRAL REPLICATION" (2023). Dissertations. 2179.
https://aquila.usm.edu/dissertations/2179