Other Immunology and Infectious Disease Commons^™

Theranostics For Antiretroviral Biodistribution And Pharmacokinetics, Brendan M. Ottemann

Theses & Dissertations

RATIONALE: Our laboratories birthed the field of human immunodeficiency virus (HIV) theranostics. The new field allows simultaneous detection (diagnostics) and treatment (therapeutic) for the identification, treatment and inevitable elimination of virus in cell and tissue compartments. By employing theranostics, antiretroviral drugs (ARVs) can be tracked in lymph nodes, gut, spleen and liver. Cellular viral reservoirs including CD4+ T cell populations and mononuclear phagocytes (MP; monocytes, macrophages, microglia and dendritic cells) along with subcellular endosomal structures can now be targeted for drug delivery bringing therapeutics to areas where virus replicates. The overarching idea rests in improving precision targeted ARV delivery. …

Mosquito Diversity And Positive Pools For The West Nile Virus In Forested Versus Non-Forested Areas, Elizabeth C. Paul

Honors Projects

The West Nile virus (WNV) is one of the leading causes of mosquito borne illness in the United States (CDC, 2018). This virus is a neurotropic pathogen that can cause fever and encephalitis. It is known that the Culex species is the primary vector for WNV. Humans infected with the WNV are typically asymptomatic. There is a small portion of individuals that experience West Nile fever which could include symptoms like high fever, vision loss, and coma (CDC, 2018). Previous studies have shown that mosquitoes tend to favor forests and wetlands (Hay et al., 1998), however, it is unknown if …

Arachidin 3 Modulation Of Lipid Metabolism In Rotavirus Infections, Stormey Wisdom

Electronic Theses and Dissertations

Rotavirus (RV) can cause severe and deadly gastroenteritis in young children, infants, and immunocompromised individuals. Previous studies have shown that arachidin 3 (A3) inhibits RV replication, and that RV replication is dependent on the presence of lipids. This study investigated the alteration of lipid metabolism by A3 in RV infected HT29.f8 cells. A decrease in the RV regulation of lipid biosynthesis genes was observed with the addition of A3 using qRT-PCR. Also, immunofluorescent and histochemical staining for neutral fats, a major component of cellular lipid droplets, revealed an increased accumulation with both RV and RV+A3 when compared to no virus …

Htlv-1 Latency-Maintenance Factor P30ii Modulates Tax-Induced Nf-Kappa B Signaling Through A P53-Regulated Mechanism, Aditi Malu

Biological Sciences Theses and Dissertations

The human T-cell leukemia virus type-1 (HTLV-1) infects CD4+ T-cells and is the etiological agent of adult T-cell leukemia/lymphoma (ATL), an aggressive and often-fatal lymphoproliferative neoplastic disease. The major transactivator protein, Tax, drives proviral gene expression and replication and plays a key role during the early-stage immortalization of T-cells by HTLV-1. Tax has also been shown to regulate many host cellular signaling pathways, including CREB/ATF, SRF, and NFκB. Another accessory viral protein p30_II acts as a latency-maintenance factor and negatively regulates proviral gene expression and replication. The p30^II protein counters Tax-dependent gene expression at the transcriptional and posttranscriptional …

An Examination Of The Potential Threat Of A State-Sponsored Biological Attack Against The United States: A Study Of Policy Implications, Courtney Anne Pfluke

Graduate Theses/Dissertations

In 2002, US Navy Seals found a list of pathogens in an Afghanistan cave that Al Qaeda had planned to use in a series of biological attacks. Unique about the discovery was that the pathogens were not limited to human ones. Six pathogens targeted livestock and four targeted crops. Despite this discovery, limited attention has been given to the possibility of a state-sponsored terrorist attack utilizing biological agents against the US population, food source, or water supply. Throughout history, biological agents have been developed for use as an offensive weapon for both states and terrorist groups. The United States may …

Development Of A Long-Acting Nanoformulation Of Dolutegravir For Prevention And Treatment Of Hiv-1 Infection, Brady Sillman

Theses & Dissertations

Dolutegravir (DTG) is a potent human immunodeficiency virus type 1 (HIV-1) integrase strand-transfer inhibitor (INSTI) with a high barrier to viral drug resistance. However, opportunities to improve its profile abound. These include extending the drug’s apparent half-life, increasing penetrance to “putative” viral reservoirs, and reducing inherent toxicities. These highlight, in part, the need for long-acting, slow effective release antiretroviral therapy (LASER ART) delivery schemes. A long-acting (LA) DTG was made by synthesizing a hydrophobic and lipophilic prodrug encased with poloxamer (P407) surfactant. This modified DTG (MDTG) reduced systemic metabolism and polarity, increased lipophilicity and membrane permeability, improved encapsulation, and formed …

Development Of A Lectin-Fc Fusion Protein With Antiviral And Anti-Cancer Activity., Matthew William Dent

Electronic Theses and Dissertations

This thesis describes the development of a novel lectin-Fc fusion protein and its antiviral and anti-cancer activity. The molecule, Avaren-Fc (AvFc), is a fusion of a variant of the actinomycete lectin actinohivin (Avaren) and the Fc region of human IgG1, and is selective for the terminal α1,2-mannose residues found at the ends of high-mannose-type glycans that can be found on the surface of certain heavily glycosylated viruses and cancer cells. Here, AvFc was found to be able to neutralize simian immunodeficiency virus as well as Hepatitis C virus with nanomolar IC₅₀ values. Furthermore, AvFc recognizes a number of cell …

Rejuvenation Of The Epigenetic Landscape Of The Aged Brain Through Manipulation Of Circulating Factors, Edward Koellhoffer

Dissertations and Theses (Open Access)

The aging population of the United States is expanding at an alarming rate. The Center for Disease Control and Prevention estimates that the population of those age 65 years and older will reach over 50 million by 2020 and will double to 100 million by 2060. This will not only put a massive strain on national healthcare resources, but will also increase the number of those who are not able to live and function independently. It is becoming increasingly vital to understand how the brain changes with age and mechanisms to possibly protect and rejuvenate the aged brain to a …

The Validity Of Medicare Claims-Based Codes To Identify Nontuberculous Mycobacterial Infection In Patients With Bronchiectasis, Jennifer Ku

OHSU-PSU School of Public Health Annual Conference

Background: Nontuberculous mycobacteria (NTM) is a disease of increasing incidence, causing permanent airway damage leading to destructive pulmonary disease. Medicare claims-based codes have been used to identify NTM infection and to evaluate trends in diagnosis and disease outcomes. However, claims-based codes to identify NTM infection have not been validated.

Methods: We linked patients with a bronchiectasis diagnosis (ICD-9-CM 494.0 or 494.1) excluding cystic fibrosis from the national 2006-2014 Centers for Medicare and Medicaid (Medicare) data to the U.S. Bronchiectasis Research Registry (BRR). The BRR is a national prospective cohort of patients with bronchiectasis, that collects detailed clinical, laboratory, microbiology and …

Non-Invasive Analysis Of The Sputum Transcriptome Discriminates Clinical Phenotypes Of Asthma, Xiting Yan

Yale Day of Data

Whole transcriptome wide gene expression profiles in the sputum and circulation from 100 asthma patients were measured using the Affymetrix HuGene 1.0ST arrays. Unsupervised clustering analysis based on pathways from KEGG were used to identify TEA clusters of patients from the sputum gene expression profiles. The identified TEA clusters have significantly different pre-bronchodilator FEV1, bronchodilator responsiveness, exhaled nitric oxide levels, history of hospitalization for asthma and history of intubation. Evaluation of TEA clusters in children from Asthma BRIDGE cohort confirmed the identified differences in intubation and hospitalization. Furthermore, evaluation of the TH2 gene signatures suggested a much lower prevalence of …

Enhancement Of Immune Response Against Bordetella Spp. By Disrupting Immunomodulation, Monica C. Gestal, Laura K. Howard, Kalyan Dewan, Hannah M. Johnson, Mariette Barbier, Clare Bryant, Illiassou Hamidou Soumana, Israel Rivera, Bodo Lina, Uriel Blas-Machado, Eric T. Harvill

Faculty & Staff Scholarship

Well-adapted pathogens must evade clearance by the host immune system and the study of how they do this has revealed myriad complex strategies and mechanisms. Classical bordetellae are very closely related subspecies that are known to modulate adaptive immunity in a variety of ways, permitting them to either persist for life or repeatedly infect the same host. Exploring the hypothesis that exposure to immune cells would cause bordetellae to induce expression of important immunomodulatory mechanisms, we identified a putative regulator of an immunomodulatory pathway. The deletion of btrS in B. bronchiseptica did not affect colonization or initial growth in the …

White-Nose Syndrome And Immune Responses In A Resistant Bat Species (Eptesicus Fuscus), Keslie Skye Naffa

Graduate Theses/Dissertations

White-nose syndrome (WNS) has had a large negative impact on bat populations across eastern North America since its arrival in 2006. Bats affected by WNS appear to die of starvation, possibly due to the increased arousals during hibernation when there is no food present to replace the energy used to arouse. During hibernation, the bat’s immune system should be suppressed. However, once a bat of a susceptible species is exposed to the fungus that causes WNS, Psuedogymnoascus destructans (Pd), the immune system seems to respond, potentially causing an elevation in metabolic rate, which may cause the bat to …

Control Efforts And Serologic Survey Of Pseudorabies And Brucellosis In Wild Pigs Of Tennessee, Lisa I. Muller, Neelam C. Poudyal, Roger Applegate, Chuck Yoest

Human–Wildlife Interactions

European wild pigs (Sus scrofa) are an introduced invasive species that now constitute a major threat to agriculture and the natural ecology of the environments they now inhabit. Wild pigs also carry many diseases known to infect wildlife, humans, and livestock. Two of these diseases, pseudorabies (PRV) and brucellosis, constitute major diseases in the United States. Better data are needed regarding the prevalence of these diseases in wild pigs to understand and manage the potential risks to wildlife, humans, and livestock. From July 1, 2011 to June 30, 2017, Tennessee Wildlife Resources Agency personnel trapped and euthanized 4,727 …

Induction Of Cerebral Hyperexcitability By Peripheral Viral Challenge: Role Of Cxcl10 Chemokine, Tiffany J. Petrisko

Graduate Theses, Dissertations, and Problem Reports (ETD)

Peripheral viral infections are po­tent comorbid factors that exacerbate neuro­degene­ration. Although the under­lying mecha­nisms have not been defined, neuronal hyperexcitability has been established as an underlying feature. Our lab has developed a preclinical model in which a viral mimetic, poly­inosinic-poly­cytidylic acid (PIC) is injected in­tra­peritoneally to induce an anti-viral acute phase response (APR). APR in turn elicits robust neuronal hyperexcitability. The present study was undertaken to characterize molecular mechanisms that mediate the development of hyperexcitability in response to PIC challenge. The analysis of brain tissue after PIC challenge revealed a robust elevation of CXCL10 chemokine, indicating its putative role in …