Influences of Host Cytokine Signaling on KSHV Infection in Tonsil-derived B Lymphocytes

<p>Kaposi sarcoma-associated herpesvirus (KSHV) is the etiologic agent of kaposi sarcoma. It is also associated with the B cell lymphoproliferative disorders, primary effusion lymphoma (PEL), multicentric Castleman disease (MCD) and KSHV inflammatory cytokine syndrome (KICS). Existing research reveals that KSHV has developed numerous strategies to alter host cytokine signaling activities to facilitate viral persistence and escape host immune surveillance.</p> <p>Despite three decades of research, there are still many questions in this field awaiting further investigation. This dissertation will investigate host cytokines as factors influencing the establishment of KSHV infection in the human tonsil. We have identified and characterized different cytokines that influence KSHV infection; with three specific aims:</p> <ol> <li>Determine whether manipulation of cytokine signaling influences KSHV infection in tonsil lymphocytes.</li> <li>Examine whether host cytokines influence B cell fate at early stages of KSHV infection</li> <li>Correlate baseline frequencies of immunological subsets, cells producing cytokines, and intracellular transcription factors with susceptibility of tonsil specimens to KSHV infection.</li> </ol> <p>We have demonstrated that host cytokines play critical roles in the establishment of infection in B lymphocytes. Interestingly, our studies demonstrated the direct effect of cytokines and the mechanism of promoting the establishment of infection through targeting plasma cells. Thus, in short, we have provided novel mechanisms for host cytokine-virus interactions for KSHV and examined the relationship between host susceptibility and cytokine functions.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Pharmaceutical Sciences

Year

2023

Author dc:creator

• Alomari, Nedaa

Contributors dc:contributor

• Dr.Jennifer E. Totonchy
• Dr.Rennolds Ostrom
• Dr.Ilhem Messaoudi
• Dr.Ajay Sharma

• Other Pharmacy and Pharmaceutical Sciences
• Pharmacy and Pharmaceutical Sciences

Repository record dc:identifier

https://digitalcommons.chapman.edu/pharmaceutical_sciences_dissertations/22

OAI identifier oai:identifier

oai:digitalcommons.chapman.edu:pharmaceutical_sciences_dissertations-1022