Examination Date
Spring 3-31-2025
Degree
Dissertation
Degree Program
Human Genetics
Examination Committee
Lucio Miele, Angela Amedee, Judy Crabtree, Ron Horswell, David Welsh, Hui-Yi Lin
Abstract
Long term immunity against viral pathogens, such as SARS-CoV-2 and Influenzas, requires identification of T cell epitopes affecting host immunogenicity. Recent reports highlight the importance of CD8+ T cell mediated immunity in conferring long term resistance to COVID-19, but research is limited due to the complexity of human T cell antigen processing and presentation. Our central hypothesis is that differences in T cell epitopes, mediated by host HLAs and mutations of viral gene products, contribute to differential clinical severity of disease outcomes, as seen in COVID-19 and Avian Influenza A(H5N1). To test this hypothesis, we conducted several investigations exploring the relationship of HLA alleles and SARS-CoV-2 in silico (chapter 2) and in the All of Us dataset (chapter 4). Notably, we identified several novel alleles associated with COVID-19 clinical severity while also confirming previously reported allelic associations. Additionally, we investigated the effects of viral variants on Long COVID by evaluating electronic medical records and patient-linked viral sequences within the Ochsner Health system (Chapter 3). Finally, we examined the application of our bioinformatics pipeline in investigating other viral pathogens, namely the highly pathogenic influenza A/H5N1 virus, by exploring cross reactive Neuraminidase N1 CD8+ epitopes (Chapter 5). Based on national estimates, approximately 2.6-14% of the population may be at increased risk of severe clinical outcomes following A(H5N1) infection. The overall goal of the proposed study is to better understand how T cell immunity affects disease outcomes in several “Big Data” clinical datasets. Our disease agnostic bioinformatic approach could help advancing precision medicine through increased surveillance/prevention strategies for high-risk populations and the development of more effective vaccine candidates with broad population coverage.
Recommended Citation
Kim, Grace J., "EXAMINING THE INFLUENCE OF HLA AND VIRAL GENETICS ON SARS-CoV-2 DISEASE SEVERITY IN LOCAL AND NATIONAL CLINICAL DATASETS" (2025). School of Graduate Studies. 9.
https://digitalscholar.lsuhsc.edu/etd_sgs/9
Dissertation Report Form