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Biochemistry, Biophysics, and Structural Biology

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Theses/Dissertations

2017

HIV

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Capacity Of Human Immunodeficiency Virus Targeting Chimeric Antigen Receptor T Cells To Eliminate Follicular Dendritic Cells Bearing Human Immunodeficiency Virus Immune Complexes, Matthew T. Ollerton Dec 2017

Capacity Of Human Immunodeficiency Virus Targeting Chimeric Antigen Receptor T Cells To Eliminate Follicular Dendritic Cells Bearing Human Immunodeficiency Virus Immune Complexes, Matthew T. Ollerton

Theses and Dissertations

An important obstacle to a functional cure for HIV/AIDS is the persistence of viral reservoirs found throughout the body in various cells and tissues. Reservoirs can be latently infected cells, or in the case of follicular dendritic cells (FDC), non-infected cells that trap infectious virus on their surface through immune complexes (HIV-IC). Although several strategies have been employed to target and eliminate viral reservoirs, they are short-lived and ineffective. In an attempt to provide a long-term approach, chimeric antigen receptor T (CAR-T) cells were designed to eliminate native HIV on FDCs. Although effective at eliminating HIV-infected cells, and halting spreading …


Utilizing Single-Molecule Fret Methods To Study Conformational Changes In Trim5Α, Margret Suzanne Bradley Jan 2017

Utilizing Single-Molecule Fret Methods To Study Conformational Changes In Trim5Α, Margret Suzanne Bradley

Master's Theses

Single-molecule FRET (smFRET) is a method by which dynamic conformational changes can be monitored in a protein microscopically and in real time. smFRET relies on the creation of FRET (Förster Resonance Energy Transfer) between small molecule fluorophores conjugated to the biomolecules of interest. FRET efficiency allows calculation of interfluorophore distances. Changes in FRET efficiency represent changes in protein conformation which can inform further structural and molecular studies of the protein of interest. For example, in the Campbell Lab, we study the protein TRIM5α, an antiretroviral cellular protein which can cause premature dissociation of the HIV capsid core by an unknown …


Elucidating Structure, Function, And Small Molecular Interactions Of Human Immunodeficiency Virus And Chikungunya Virus, Kristin Nicole Slater Jan 2017

Elucidating Structure, Function, And Small Molecular Interactions Of Human Immunodeficiency Virus And Chikungunya Virus, Kristin Nicole Slater

Wayne State University Theses

Abstract HIV-1:

Human immunodeficiency virus-1 (HIV-1) is a widespread, incurable retrovirus known to cause

immunodeficiency and a shortened life span. Despite successful treatment methods, HIV-1

frequently mutates, resulting in antiviral resistance. Many therapies target the HIV-1 protease

(PR), which is responsible for cleaving the viral polyprotein essential for its life cycle. HIV-1 PR

often evades treatment by way of mutations and less commonly through residue insertions. We

have identified a clinical isolate with a five residue insertion between residues 28 and 29.

Through molecular dynamics simulations we analyzed the protease protein structure and

determined that the residue insertion created a …