Viral protein r (Vpr) of Human immunodeficiency virus type 1 (HIV-1) plays an important role in the ability of the virus to infect cells and cause disease. Two polymorphisms to Vpr have been shown to result in differences in disease progression in infected individuals. R36W tends to result in rapid disease progression while R77Q results in long-term non-progression. In order to better understand how these polymorphisms result in these different disease phenotypes, our lab has recently shown that in cell culture, the R36W polymorphism results in increased viral replication and greater induction of cell death. On the other hand, infection with R77Q results in increased G2 cell cycle arrest and increased induction of apoptosis. In this thesis, we have attempted to study how these two polymorphisms affect the ability of HIV-1 to cause cell death in primary CD4+ cells. We show that infection by a Vpr knockout virus results in increased apoptosis while infection with R77Q and R36W result in decreased apoptosis. Additionally, R77Q infection results in increased p24 production. Further, we attempted create a Rag2-/- γc-/- humanized mouse model in order to better study roles of these polymorphisms in vivo. An additional goal of this thesis was to characterize twelve novel Bacillus anthracis bacteriophage. B. anthracis is gram positive, anaerobic, rod best known for being the causative agent of anthrax. Bacteriophage, viruses that infect bacteria, have been used to identify bacterial contamination and to treat infection. Herein, we report the isolation, sequencing, and characterization of twelve novel phages that infect B. anthracis. The genomes were annotated using DNA Master and BLASTp. Hypothetical proteins were analyzed with Phyre2 to predict possible functions based on protein structure, revealing over 100 new predicted functions. Dotplot generation showed that these phages group into four distinct clusters. By running the major portal protein of one representative of each cluster through BLASTp, we have identified the closest relatives to our novel phages and placed them into their respective genera and groups.
College and Department
Life Sciences; Microbiology and Molecular Biology
BYU ScholarsArchive Citation
Fairholm, Jacob D., "The Effects of Polymorphisms of Viral Protein R of HIV-1 on the Induction of Apoptosis in Primary Cells and the Characterization of Twelve Novel Bacillus anthracis Bacteriophage" (2022). Theses and Dissertations. 9627.
HIV-1, Vpr, AIDS, Rag2-/- γc-/- humanized mice, apoptosis, primary CD4+ cells Bacillus anthracis, bacteriophage