Biophysical characterization of non-canonical viral nucleic acid interactions with human proteins
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Date
2025
Authors
Gemmill, Danielle L.
University of Lethbridge. Faculty of Arts and Science
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Publisher
Lethbridge, Alta.: University of Lethbridge, Dept. of Chemistry and Biochemistry
Abstract
Viruses are a replicative, paradoxical genetic element that are critical to our survival, but are also a significant burden to public health. Viruses that cause disease in humans continuously evolve to avoid counteroffensive measures from our immune system. Both DNA and RNA viruses have developed various methods to optimize their replication and spread to a host, such as genomic mutations that renders host antibodies ineffective, or by possessing structure that confers an advantage for propagation of virions. Moreover, the structures that viruses possess within their genomes alone provide the virus with the ability to hijack host proteins for replicative and propagation purposes by hijacking and suppression of host cellular functions, altogether benefitting the viral lifecycle. This thesis focuses on the identification of the viral nucleic acid structures that DNA and RNA viruses possess that allow them to replicate and avoid host defenses, and as well, identify host proteins being hijacked by these structures. Specifically, I characterize conserved regions of Zika virus known as the terminal regions that regulate transcription and translation of the viral genome and perform immunoprecipitation pulldown assay to identify host binding partners interacting with them that are critical for viral replication. I also elucidated a non-canonical structure (G-quadruplex) in these terminal regions that interacts with host proteins that could be utilized as a potential anti-viral target, and further, show that G-quadruplexes are also present in DNA viruses such as Mpox virus. I show that TMPyP4, a G-quadruplex binding small molecule, interacts with the Mpox G-quadruplexes and reduces viral protein production.
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Keywords
biophysics , Zika virus , Mpox virus , RNA , protein , RNA-protein interactions , G-quadruplex