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Full-Text Articles in Diseases

Engineering Yeast To Evaluate Human Proteins Involved In Selective Rna Packaging During Hiv Particle Production, Ryan M. Bitter Dec 2018

Engineering Yeast To Evaluate Human Proteins Involved In Selective Rna Packaging During Hiv Particle Production, Ryan M. Bitter

Master's Theses

Despite recent advances in antiretroviral therapy, nearly 37 million people continue to live with human immunodeficiency virus (HIV). Basic and applied research on the assembly of HIV could be enhanced by using a genetically tractable organism, such as yeast, rather than mammalian cells. While previous studies showed that expression of the HIV Gag polyprotein in Saccharomyces cerevisiae spheroplasts resulted in the production of virus-like particles (VLPs), many questions regarding the utility of yeast in HIV assembly remain uninvestigated. Here, we report use of S. cerevisiae for both the production of VLPs with selectively packaged RNA and to evaluate the human …


Hiv Integrase Inhibitor Pharmacogenetics And Clinical Outcomes: An Exploratory Association Study, Derek E. Murrell Aug 2018

Hiv Integrase Inhibitor Pharmacogenetics And Clinical Outcomes: An Exploratory Association Study, Derek E. Murrell

Electronic Theses and Dissertations

As HIV is now primarily a chronic condition, treatment is given life-long with changes as necessitated by alterations in tolerability and efficacy. Thus, personalized medicine may be useful in the prevention of unnecessary drug exposure and avoidable side effects. Three of the four currently available HIV integrase strand transfer inhibitors (INSTIs), raltegravir, elvitegravir, and dolutegravir, are widely utilized antiretrovirals in the USA and exhibit variations in outcomes among subjects. To interrogate differences among subjects receiving these drugs, we investigated the association of several single nucleotide polymorphisms (SNPs) with drug exposure, clinical outcomes, and subject-reported adverse events. HIV+ adults (≥18 years …


Tat Controls Transcriptional Persistence Of Unintegrated Hiv Genome In Primary Human Macrophages., Beatrix Meltzer, Deemah Dabbagh, Jia Guo, Fatah Kashanchi, Mudit Tyagi, Yuntao Wu May 2018

Tat Controls Transcriptional Persistence Of Unintegrated Hiv Genome In Primary Human Macrophages., Beatrix Meltzer, Deemah Dabbagh, Jia Guo, Fatah Kashanchi, Mudit Tyagi, Yuntao Wu

Medicine Faculty Publications

In HIV infected macrophages, a large population of viral genomes persists as the unintegrated form (uDNA) that is transcriptionally active. However, how this transcriptional activity is controlled remains unclear. In this report, we investigated whether Tat, the viral transactivator of transcription, is involved in uDNA transcription. We demonstrate that de novo Tat activity is generated from uDNA, and this uDNA-derived Tat (uTat) transactivates the uDNA LTR. In addition, uTat is required for the transcriptional persistence of uDNA that is assembled into repressive episomal minichromatin. In the absence of uTat, uDNA minichromatin is gradually silenced, but remains highly inducible by HDAC …