Host and Viral Molecular Patterns Relevant to Pathogenicity and Immunity

Stabell, Alexander Christian

Graduate Thesis Or Dissertation

Host and Viral Molecular Patterns Relevant to Pathogenicity and Immunity Public Deposited

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Citeable URL: https://scholar.colorado.edu/concern/graduate_thesis_or_dissertations/vd66vz98m

Abstract

Patterns in nature, many going unnoticed, are a defining characteristic of life. In this thesis, I will describe four studies that I have completed during my doctoral work. These will highlight how both host immune system and viral pathogens harness non-random biological patterns to aid in immunity or increase pathogenicity, respectively. Chapter 2 will describe the evolutionary history of a component of the primate innate immune system, Schlafen11, and its involvement in the defense against viruses. I attempt to show that Schlafen11 takes advantage of the pattern of non-optimal codon usage of HIV-1 transcripts in order to inhibit viral replication. In Chapter 3, I will further expand on this story, showing that the mechanism of action of Schlafen11, as well as a related paralog Schlafen12L, targets viral transcripts during translation. Schlafens appear to act in a mechanism akin to No-go decay, where transcripts that are translated inefficiently---inducing ribosomal pausing---appear to be targeted for degradation by Schlafen11 and Schlafen12L. This No-go-like mechanism extends beyond just viral transcripts insofar that host transcripts that are predicted to be translated inefficiently are also targeted for degradation by these Schlafens. In Chapter 4, I turn to studying how the dengue virus protease recognizes and cleaves specific 8-amino acid peptide motifs of host proteins in order to restructure the cellular environment to aid in viral replication. Finally, in Chapter 5, I describe a specific instance in which the dengue virus protease may have influenced the evolution of a protein involved in the innate immune response against dengue, the STimulator of INterferon Genes (STING).

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