Date of Award

Fall 12-7-2023

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.

Available for download on Thursday, January 01, 2026

Included in

Biochemistry Commons

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