Publication Date
2024
Document Type
Thesis
Committee Members
Abimbola O. Kolawole, Ph.D. (Advisor); Quan Zhong, Ph.D. (Committee Member); Dan R. Halm, Ph.D. (Committee Member)
Degree Name
Master of Science (MS)
Abstract
Human Astroviruses (HAstV) are positive sense non-enveloped single stranded RNA viruses. HAstV is divided into classical (serotype 1-8) and non-classical (HAstVMLB 1-3 and HAstV-VA1-5) astroviruses. Classical HAstV is known to cause diarrhea in children, elderly, and immunocompromised patients. Additionally, the etiology of nonclassical HAstV remains unknown. However, recent studies have implicated non-classical HAstV closely associated with immunocompromised patients diagnosed neurological diseases like acute encephalitis. The mechanisms by which HAstV cause diarrhea is currently unknown. Aquaporins (AQPs) are integral membrane proteins that regulate the movement of water and small uncharged molecules across the cell membrane in response to osmotic gradients. Tight junctions (TJs) are intercellular barriers that are located between neighboring epithelial cells. These intercellular barriers are responsible for regulating the movement of water and solutes across the cell membrane. Thus, we hypothesized that AQPs and TJPs play crucial roles in virus-induced diarrhea. For this purpose, we utilized two cell lines (Caco-2 and Huh 7.5) and analyzed the expression of all thirteen human AQPs (AQP0‐12) in HAstV-1 and HAstV-MLB2 infected cells. We demonstrate that AQP expression in Caco-2 and Huh 7.5 cells largely varied in both gene and protein expressions. Astrovirus infection significantly increased the expression of AQP iv 3, 4 and 10 after 3 days post infection. Additionally, there was an increase of in the genome expression of TJPs in HAstV-1 infected cells. However, TJP expression decreased in HAstV-MLB2 infected cells. Furthermore, there was a decrease in the structural integrity of TJs, determined by measuring the trans-epithelial electric resistance (TEER), in HAstV1 infected Caco-2 cells when compared to the mock infected cells. These findings suggests that AQP expression and TJ integrity may play a role in HAstV-induced diarrhea. However, the specific role that these AQPs and TJPs play during HAstV requires further investigation.
Page Count
80
Department or Program
Department of Biological Sciences
Year Degree Awarded
2024
Copyright
Copyright 2024, all rights reserved. My ETD will be available under the "Fair Use" terms of copyright law.
