Graduation Year
2024
Document Type
Dissertation
Degree
Ph.D.
Degree Name
Doctor of Philosophy (Ph.D.)
Degree Granting Department
Public Health
Major Professor
Kristi M. Miley, Ph.D.
Co-Major Professor
Jaime A. Corvin, Ph.D.
Committee Member
Thomas McDonald, MD.
Committee Member
Kathleen Pope, MD.
Keywords
arbovirus, cardiac organoid, cardiomyocyte, iPSC
Abstract
Chikungunya Virus (CHIKV) is a single stranded RNA alphavirus primarily vectored by Aedes aegypti and Aedes albopictus mosquitos. CHIKV has circulated in tropical and sub-tropical regions of Africa and Asia, but outbreaks in the past two decades have seen the virus spread to Europe, South America, and the Caribbean. Disease from CHIKV infection typically results in fever, malaise, and sometimes debilitating arthralgia. However, there are concerning abnormal presentations that affect the human heart, including myocarditis, heart failure, and death. These symptoms are seen in all age groups and sexes and are not connected to particular strains or mutations in the virus. Studying CHIKV infection of the heart is challenging, as mouse models generally require higher than clinically relevant viral loads to exhibit symptoms or are knockouts of vital immune response systems. Therefore, another potential model system is induced pluripotent stem cell (iPSC) derived cardiomyocyte monolayers or cardiac organoids. CHIKV infections of iPSC derived cardiomyocytes revealed that this model generally follows what is seen in the clinical case literature, featuring high CHIKV viral titers, arrythmia, increased levels of immune factors, and increased levels of cardiac biomarkers of damage. Additionally, specific strains and lineages of CHIKV did not confer a statistically higher level of cardiac damage risk. However, when breaking down the data to potential sex-based risk factors, the immunological results did not align to what is seen in the clinical case data, implying that the model failed to replicate sex-based differences. Future studies will need to add sex hormones to the culture to see if this issue can be alleviated. CHIKV infections of iPSC derived semi-vascularized cardiac organoids revealed that CHIKV first invades the endothelial layer of the organoids, at which point the virus was not able to efficiently replicate. This is consistent with other studies and clinical data. Thus, the cardiac organoid is a possible model system to study CHIKV, and other viral infections, in the future.
Scholar Commons Citation
Traverse, Elizabeth M., "Chikungunya Pathogenesis in Cardiac Tissues and its Evaluation in Stem Cell Derived Cardiac Models" (2024). USF Tampa Graduate Theses and Dissertations.
https://digitalcommons.usf.edu/etd/11206
