Abstract

Turkey hemorrhagic enteritis virus (THEV) is an adenovirus (AdV) that causes hemorrhagic enteritis (HE) in turkeys, a debilitating disease affecting predominantly 6-12-week-old turkey poults characterized by immunosuppression (IMS) and intestinal lesions leading to bloody diarrhea. Although a naturally-occurring avirulent THEV strain has been adopted as live vaccine and has proven effective at preventing HE in turkeys, it still retains its immunosuppressive ability. Thus, vaccinated birds are rendered more susceptible to opportunistic infections and death than unvaccinated cohorts, leading to substantial economic losses. This dissertation focuses on elucidating both host and viral factors mediating THEV-induced IMS in turkeys. As THEV gene expression was woefully understudied, characterization of the viral transcriptome (splice map) was essential to allow the study of individual viral gene functions for possible roles in THEV-induced IMS. Using RNA sequencing, 3' rapid amplification of cDNA ends (3'-RACE), cDNA cloning, and quantitative PCR (qPCR), I characterized the first transcriptomic (splice) map of THEV, uncovering several novel transcripts and open reading frames, some of which may likely be found to mediate THEV-induced IMS in future research. Additionally, I also utilized RNA sequencing, qPCR, and several bioinformatics tools to perform the first transcriptomic study of THEV-infected host cells to uncover the host cell pathways and processes modulated by THEV during infection that may contribute to IMS. Since THEV primarily infects crucial immunofunctional cells (B-cells and macrophages), THEV-induced IMS has been attributed to apoptosis or necrosis of infected cells; however, the specific mechanism(s) of induction was unclear. In this work, I showed that THEV induces a significant increase in cellular breakdown pathways while downregulating structures and processes for cell maintenance. Specifically, I discovered that THEV infection triggers many pro-apoptotic cellular processes such as the endoplasmic reticulum (ER) unfolded protein response and its associated ER-associated protein degradation (ERAD) pathway while suppressing cell maintenance processes such as ribosome biosynthesis and DNA repair. Moreover, I successfully constructed a full-length genomic clone of the THEV genome using a Gibson DNA assembly-based method to allow knock out or inactivation of target genes for reverse genetic studies of the functions of these genes in THEV pathogenesis. While cloning the viral genome, I discovered and characterized a novel shorter variant of the THEV vaccine strain distinguished by a 288 bp deletion at 3' terminus of the genome.

Degree

PhD

College and Department

Life Sciences; Microbiology and Molecular Biology

Rights

https://lib.byu.edu/about/copyright/

Date Submitted

2025-07-31

Document Type

Dissertation

Keywords

immunosuppression, RNA splicing, apoptosis, hemorrhagic enteritis

Language

english

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