Date of Award

1-1-2017

Language

English

Document Type

Master's Thesis

Degree Name

Master of Science (MS)

College/School/Department

Department of Chemistry

Content Description

1 online resource (ii, ix, 46 pages) : illustrations (some color)

Dissertation/Thesis Chair

Daniele Fabris

Committee Members

Jia Sheng, Alexander Shekhtman

Keywords

Virus diseases, Transcription factors

Subject Categories

Chemistry | Microbiology

Abstract

The characterization of host-virus relationships is essential for understanding the process of viral replication and driving the development of effective viral targeting strategies. In this work, I tested the hypothesis that ribonucleic acid (RNA) post-transcriptional modifications (PTMs) may play a significant role in defining host-virus interactions. The model system consisted of a yeast strain capable of harboring the endogenous L-A virus, which allowed me to evaluate the possible involvement of PTMs in the process of cellular immunity to virus-borne toxicity. A mass spectrometry-based platform was utilized to compare the global PTM profile of wild-type yeast with those of the same strain infected with L-A virus, or containing both L-A virus and its M1 satellite –the condition necessary to observe immunity. These experiments uncovered a set of PTMs that were overexpressed when immunity was present. A strategy that involved knocking down specific genes involved in the biogenesis of such PTMs and monitoring the effects on immunity and viral replication was implemented to further investigate the possible correlation between immunity and PTM regulation. Although the limited scope of a M.S. thesis did not allow me to complete the entire exploration, the initial results were very promising and indicated that the presence of specific PTMs was essential to maintaining cellular immunity. This preliminary work thus established the foundations for understanding the involvement of PTMs in virus-host interactions responsible for conferring immunity. Future work will address the mechanism at the molecular level by mapping the location of such PTMs onto L-A and M1 RNAs, which will enable correlations with the processes mediated by the observed sequences. The insights obtained from the L-A virus system will be applicable to many RNA viruses responsible for human diseases. For this reason, I believe that these studies have the potential of uncovering new potential targets for developing antivirals aimed at inhibiting PTM-mediated processes.

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