Date of Award

Fall 1-2021

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Pharmaceutical Sciences

First Advisor

Dr. Jennifer E. Totonchy

Second Advisor

Dr. Innokentiy Maslennikov

Third Advisor

Dr. Ajay Sharma

Fourth Advisor

Dr. Moom Roosan

Abstract

The enigma of Kaposi Sarcoma Herpes Virus infection, and its persistence despite a quarter century of research on the virus, has given rise to an immediate need for addressing fundamental questions about basic immunology and virology knowledge regarding this virus. Kaposi Sarcoma Herpes Virus (KSHV), also known as Human Herpesvirus 8 (HHV8), is the etiological agent of Kaposi Sarcoma (KS) and other lymphoproliferative cancers, such as Multicentric Castleman’s Disease (MCD), Primary Effusion Lymphoma (PEL), and a newly discovered rare disease called KSHV Inflammatory Cytokines Syndrome (KICS). Epidemic KS, also known as AIDS-KS, is the most common cancer in untreated HIV patients. This epidemic in western countries mostly affects the homosexual population, while in the malaria-belt, both men and women can be affected equally. All forms of diseases caused by KSHV are uniformly fatal highlighting the need for research into KSHV virology for the identification of possible druggable targets to address the public health burden and help further develop vaccines, therapies, or treatments.

The thesis presented herein will focus on the study of early infection events and the persistence of infection within the oral cavity. We have identified and characterized virion-associated factors critical for the earliest stages of KSHV infection; in three specific aims:

  1. Examining Host-Specific Differences and Viral Tropism in KSHV Infection of Tonsil-Derived B Lymphocytes

  2. Validating the Proteomic Composition of KSHV Virions

  3. Establishing the Contribution of KSHV-ORF11 Tegument Protein in de novo

    Infection of B Lymphocytes.

We have demonstrated that gamma-herpesvirus conserved tegument factors play critical but uncharacterized roles in the establishment of infection in B lymphocytes, and that utilizing our study model provides us with the unique chance to observe this infection process at an early stage. Thus, in short, we have attempted to provide an answer to the long-forgotten questions within the field of KSHV virology about the proteins the virion packages and introduces in early stages of infection and what that could mean in the bigger picture for the host -pathogen interactions.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Available for download on Sunday, January 30, 2022

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