Determining the Role of Cellular Glycosphingolipid Biosynthesis on Influenza Virus Infectivity
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Issue Date
2018-08
Authors
Williams, Clare '18
Degree
MS in Molecular Biosciences
Advisor
Yager, Eric J
Committee Members
Malik, Meenakshi
Sharifi, H. John
LaRocca, Timothy
Sharifi, H. John
LaRocca, Timothy
Journal Title
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Volume Title
Abstract
Influenza A virus (IAV) is able to mutate rapidly and has therefore developed resistance to available antivirals that target viral proteins. Glycosphingolipids (GSLs) are present in all eukaryotic cells and have been known to play critical roles during the lifecycle of various enveloped viruses. The enzyme glucosylceramide synthetase (GCS) is a key enzyme intermediate during GSL biosynthesis and could play a role in the generation of influenza virus particles. Various stages of the IAV lifecycle were analyzed in the absence of GCS; fluorescence microscopy was used to look at viral binding, gene expression and protein synthesis of IAV proteins was analyzed, and infectious virus particles were counted through the use of TCID50 and plaque assays. Host factor gene expression was also analyzed over the course of infection. It was found that GCS plays a role in the initial binding of IAV to the surface of host cells. This may lead to a decrease in IAV gene expression and protein production, and ultimately the amount of infectious virus released. It was also found that IAV upregulates GCS expression during infection. These findings can be used to further the understanding of how IAV interacts with GSLs and potentially lead to the development of a vaccine or antiviral treatment for influenza virus infection.
Citation
Williams C. Determining the role of cellular glycosphingolipid biosynthesis on influenza virus infectivity [thesis]. Ann Arbor (MI): Proquest LLC; 2018. 61 p.
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