Immunology of Infectious Disease Commons^™

Nanoparticle Carriers Enhance The Prophylactic Antiviral Effects Of Dsrna In Vitro And Ex Vivo, Shayne Oberhoffner, Stephanie Dewitte-Orr, Starla Richardson, Leah Haile, Dominique Daniels, Erin Cooper, Aizah Ijaz, Janet Velasquez Perez, Mathilde Peruzzi, Bertrand Collet, Paul Craig, Kristof Jenik

Theses and Dissertations (Comprehensive)

Aquaculture now outpaces traditional capture fisheries as the world population and demand for sustainable protein sources increases. Wild and farmed species are increasingly susceptible to pathogen spread as global temperatures rise and stocking densities increase. Despite the devastating losses experienced by aquaculture due to viral infections, there remain few effective prophylactic antiviral therapeutics. Long double-stranded (ds)RNA is a uniquely viral molecule produced by nearly all viruses during their replication cycle, and its detection by salmonids like rainbow trout (Oncorhynchus mykiss) and chinook salmon (Oncorhynchus tshawytsha) leads to the establishment of a defensive antiviral state. Previous in vitro studies demonstrated a …

Expanding Inducible Epithelial Resistance Against Pneumonia: Novel Virus, Novel Receptor, Michael Longmire

Dissertations and Theses (Open Access)

Pneumonia is the leading infectious cause of death worldwide and presents a continuing risk among immunocompromised patients. Our work has been focused for many years on the phenomenon of inducible epithelial resistance, where activation of the innate immune response in the airway epithelium is necessary and sufficient to produce a pathogen-killing but self-protective environment to prevent severe disease. Inducible resistance is pathogen-agnostic and has been demonstrated against an array of respiratory infections. We achieve this using a combination of pattern recognition receptor agonists – Pam2CSK4 and ODN M362 being the current formulation – which produce synergistic levels of pathogen reduction …

The Role Of Host Factor Sptbn1 In Hiv-1 Capsid Uncoating In Human Microglial Cells, Callie Marie Fry

Graduate Theses/Dissertations

HIV-1 is the virus that causes acquired immunodeficiency syndrome (AIDS), and currently, there is no cure once an individual is infected. The development of new drugs targeting HIV-1 replication steps is essential for keeping viral loads low or undetectable to prevent further transmission. An attractive replication step for new drug targets is viral capsid uncoating, where the virus loses the protein structure encapsulating the genome. The exact mechanism of capsid uncoating is unknown; however, several host-factors may be involved including protein SPTBN1. Recent studies have shown a significant decrease in viral infectivity when SPTBN1 is knocked down, yet its role …

How Individuals’ Opinions Influence Society’S Resistance To Epidemics: An Agent-Based Model Approach, Geonsik Yu, Michael J. Garee, Mario Ventresca, Yuehwern Yih

Faculty Publications

Background: Protecting public health from infectious diseases often relies on the cooperation of citizens, especially when self-care interventions are the only viable tools for disease mitigation. Accordingly, social aspects related to public opinion have been studied in the context of the recent COVID-19 pandemic. However, a comprehensive understanding of the effects of opinion-related factors on disease spread still requires further exploration. Methods: We propose an agent-based simulation framework incorporating opinion dynamics within an epidemic model based on the assumption that mass media channels play a leading role in opinion dynamics. The model simulates how opinions about preventive interventions change over …

Intestinal Microbiome, Fecal Fermentation Profile, And Health Indices In Hiv Infected Men Versus Non-Infected Controls, Mary Andreae, Mary C. Andreae Mrs

Electronic Theses and Dissertations

Many HIV-positive (HIV+) males on Highly Active Anti-Retroviral Therapy (HAART) experience metabolic abnormalities, including Non-Alcoholic Fatty Liver Disease (NAFLD) and lipodystrophy. The intestinal microbiota and short chain fatty acids (SCFA), participate in bidirectional communication with their host. Dysbiosis in HIV+ males on HAART demonstrate a Prevotella-rich enterotype shaped by multiple factors including, medications, adiposity, diet, intestinal permeability, and lifestyle; our objective was to investigate these factors. 19 HIV+ and 21 HIV- males were enrolled. BMI and hip-to-waist ratio (H:W) were obtained, and FibroScan for liver health. Intestinal permeability markers Claudin-21, flagellin, and intestinal fatty acid binding protein (IFABP) in …

Sars-Cov-2: Tale Of A Microscopic Murderer, Josiah P. Garner

Quest

Independent Study

Research in progress for BIOL1406: Biology for Science Majors I

Faculty Mentor: Amina Tassa, Ph.D.

I am delighted to introduce Josiah Garner’s “SARS-CoV-2: Tale of a Microscopic Murderer.” This independent study assignment explores the impact of a novel, deadly, and worldwide virus. The assignment also examines the fast development of vaccines to control the spread and reduce the symptoms of the virus.

Josiah’s paper focuses on the early history of the emergence of COVID-19, the world response, and vaccine development. He demonstrates critical thinking skills and effectively utilizes various research methods to obtain and communicate his information. Josiah …

Antibody-Dependent Enhancement Activity Of A Plant-Made Vaccine Against West Nile Virus, Amber M. Paul, Haiyan Sun, Dhiraj Acharya, Huafang Lai, Junyun He, Fengwei Bai, Qiang Chen

Publications

West Nile virus (WNV) causes annual outbreaks globally and is the leading cause of mosquito-borne disease in Unite States. In the absence of licensed therapeutics, there is an urgent need to develop effective and safe human vaccines against WNV. One of the major safety concerns for WNV vaccine development is the risk of increasing infection by related flaviviruses in vaccinated subjects via antibody-dependent enhancement of infection (ADE). Herein, we report the development of a plant-based vaccine candidate that provides protective immunity against a lethal WNV challenge mice, while minimizes the risk of ADE for infection by Zika (ZIKV) and dengue …

Interactions Between Hiv And Opioids On Antiretroviral Accumulation, The Blood Brain Barrier, And The Inflammatory Response In The Brain., Kara Rademeyer

Theses and Dissertations

The complex mechanisms related to HIV infection, neurodegeneration, and chronic neuroinflammation collectively describe neuroHIV (Hauser et al. 2007; Chang et al. 2014; Smith et al. 2014). Specifically, opioid abuse, poor penetration of antiretroviral (ARV) drugs, chronic inflammation and neuronal injury/degeneration are all implicated in neuroHIV (Fantuzzi et al. 2003; Letendre et al. 2004; Verani et al. 2005; Duncan and Sattentau 2011; Hong and Banks 2015; Simoes and Justino 2015; Olivier et al. 2018; Murphy et al. 2019; Osborne et al. 2020). For the first time, we demonstrate that morphine, fentanyl, and methadone in vivo alter the brain accumulation of ARVs, …

Generation Of Chimeric Rhinoviruses Presenting Sars-Cov-2 Broadly Neutralizing Epitopes And Their Antigenicity Characterization, Danish Ansari

Biotechnology Theses

The global COVID pandemic is not yet fully under control as there were over 21 million new cases of SARS-CoV-2 infections and over 50,000 deaths globally as of January of 2022. A heavily mutated variant of concern, Omicron is responsible for most of these cases which demands an urgency for a new vaccine. NIH reports over 180 vaccine candidates that use various strategies currently in development. However, a recurring concern with these vaccines is that the continuous viral mutations decrease the efficacy of vaccines. Therefore, we proposed to construct a human rhinovirus (HRV) based chimeric virus containing highly conserved, broadly …

Proposing An Rna Interference (Rnai)-Based Treatment For Human Immunodeficiency Virus (Hiv) By Analyzing The Post-Transcriptional Gene Targeting Of Sars-Cov-2, Hepatitis C Virus, And A549 Lung Cancer Cells, Arjun Jagdeesh

UROP Posters

Human Immunodeficiency Virus (HIV) is a retrovirus that infects CD4+ T cell lymphocytes in humans, leading to the development of Acquired Immunodeficiency Syndrome (AIDS) if left untreated. While current treatment methods, including antiretroviral combination treatments, effectively limit HIV replication, HIV can evade these treatments due to its high mutation rate. Long-term antiretroviral treatment can also be toxic to patients, meaning patients would benefit from a new mechanism of HIV treatment. RNA interference (RNAi) is an antiviral pathway found in mammals, plants, and insects that involves a small-interfering RNA that is incorporated into a protein complex called the RNA-induced Silencing Complex …

The Mechanisms Of Mitochondrial Dysfunction In T Cell Aging During Chronic Viral Infection, Madison B. Schank

Electronic Theses and Dissertations

Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections induce a myriad of disturbances to CD4 T cell functions, including mitochondrial compromise, excessive inflammation, increased telomeric DNA damage and attrition, cellular exhaustion and senescence, and accelerated aging. In this dissertation, the mechanisms underlying metabolic failure, accelerated aging, and cellular dysfunctions were evaluated in CD4 T cells from healthy subjects (HS) treated with a telomere-targeting drug (KML001) or HCV-infected individuals or people living with HIV (PLHIV) compared to HS. We observed that KML001-induced telomere injury resulted in mitochondrial swelling and decreased mitochondrial membrane potential, cellular respiration, mitochondrial DNA (mtDNA) copy …

Investigating The Pi3k/Akt/Atm Pathway, Telomeric Dna Damage, T Cell Death, And Crispr/Cas9-Mediated Gene Editing During Acute And Chronic Hiv Infection, Sushant Khanal

Electronic Theses and Dissertations

Human Immunodeficiency Virus (HIV) infection initiates major metabolic and cell- survival complications. Anti-retroviral therapy (ART) is the current approach to suppress active HIV replication to a level of undetected viral load, but it is not a curative approach. Newer and sophisticated gene editing technologies could indeed be a potent antiviral therapy to achieve a clinical sterilization/cure of HIV infection. Chronic HIV patients, even under a successful ART regimen, exhibit a low-grade inflammation, immune senescence, premature aging, telomeric DNA attrition, T cell apoptosis, and cellular homeostasis. In this dissertation, we investigated CD4 T cell homeostasis, degree of T cell apoptosis, an …

Covid Susceptibility And Severity Correlation With The Ace2 Gene, Natalie Taylor

Thinking Matters Symposium

A wide spectrum of susceptibility and severity of infection has been observed among COVID-19 patients. While some individuals remain unaffected by the Sars-Cov-2 virus, others have contracted the virus multiple times with varying levels of severity. This poster reviews some of the research demonstrating a link between the susceptibility of the Sars-Cov- 2 virus and the severity of infection, and a specific gene called ACE2. The ACE2 gene encodes an angiotensin-converting enzyme that acts as a functional receptor for the spike glycoprotein receptor binding domain of the coronavirus and severe acute respiratory syndrome coronaviruses. ACE2 presents numerous amino acid variants …

Physician's Attitudes On Pulmonary Rehabilitation Following Covid-19: A Brief Perspective From A Developing Country, Ivan Cherrez-Ojeda, Emanuel Vanegas, Miguel Felix, María José Farfán Bajaña, Azza Sarfraz, Zouina Sarfraz, Genesis Camacho, Alanna Barrios-Ruiz, Jack Michel

Department of Paediatrics and Child Health

Despite the uncertainty about the follow up of COVID-19 survivors, there is a growing body of evidence supporting specific interventions including pulmonary rehabilitation, which may lead to a reduced hospital stay and improved overall respiratory function. The aim of this short report was to assess the attitudes toward pulmonary rehabilitation following COVID-19 among Ecuadorian physicians. A cross-sectional study was conducted, in which a 5-question survey was used to assess the level of agreement to specific statements with a 5-point Likert scale. Out of the 282 participants, 48.2% (n=136) were male, with a mean of 12.6 (SD=11.3) years of experience. More …

Implementation Of A Drive-Through Covid-19 Mass Vaccination Site: Experiences From Louvax–Broadbent In Louisville, Kentucky, Ruth Carrico, Sarah Beth Hartlage, Valenchia Brown Msn, Aprn, Fnp-C, Sarah M. Bishop, Luanne Didelot, William Hayden, Beverly Williams Coleman, Sarah Tan, Delanor Manson, Kellie Kane, Dawn Balcom, Paul Kern

The University of Louisville Journal of Respiratory Infections

Background: Response to the COVID-19 pandemic has required innovative approaches to vaccination, including methods to rapidly and safely immunize communities. A major challenge to such a response involved access to untapped healthcare worker resources. The Louisville, Kentucky, response involved the use of a large volunteer workforce to supplement local public health employees in planning and implementing a large-scale drive-through vaccination event. The objective of this manuscript was to outline processes involved in training a mass immunization workforce and implementating a large-scale COVID-19 community vaccination.

Approach: Competency-based and standardized training was provided for every volunteer before working their shift. Volunteers worked …

Covid-19 Vaccine Diplomacy In West Africa: Empathetic Soft-Power Or Neocolonial Intentions?, Mary Sperrazza

Independent Study Project (ISP) Collection

With the impending roll-out of COVID-19 vaccines, many questions have been raised concerning the roll-out of the vaccines beyond the Global North. While some countries across the Global South have been able to purchase limited numbers of vaccines; many countries in the Global South remain highly or entirely dependent on various programs for the distribution of vaccines, such as the COVID-19 Vaccines Global Access (COVAX) program. Another means of distribution is of individual countries of the Global North that have either higher purchasing power or are producers of one or more vaccines that have begun donating an allocated amount of …

Host Cell Responses To Zika Virus Infection, Bikash Ranjan Sahoo

School of Veterinary and Biomedical Sciences: Dissertations, Theses, and Student Research

The re-emergence of Zika virus (ZIKV) in 2015 as a significant human pathogen causing neurological diseases in infants as well as adults is a serious global health concern. A clear understanding of the mechanisms involved in ZIKV replication in infected host cells as well as the host responses to virus infection are keys to the development of therapeutic strategies against ZIKV. Studies conducted in this dissertation demonstrate that ZIKV infection induces the activation of mTOR signaling cascade that promotes viral protein accumulation and infectious progeny production. While both mTORC1 and mTORC2 are essential for ZIKV replication, the observation that depletion …

Development Of Vaccines And Antivirals Against Zika Virus, Aryamav Pattnaik

School of Veterinary and Biomedical Sciences: Dissertations, Theses, and Student Research

The re-emergence of Zika virus (ZIKV), an arbovirus, poses a major global human health concern because of its ability to cause congenital abnormalities and neurological diseases. While many candidate vaccines and antiviral drugs are in the developmental pipeline, none have been approved for use against ZIKV infection. This dissertation describes the characterization of one vaccine and two antiviral drug candidates against ZIKV infection. A bacterial ferritin-based nanoparticle vaccine, termed zDIII-F, is designed to display multiple copies of ZIKV E protein domain III on its surface. These stable nanoparticles are shown to induce robust antibody-mediated protection against lethal ZIKV infection in …

Assessment Of Pathogenic Changes In The Gut-Liver Axis In Plwh With Heavy Alcohol Drinking And Gut Dysbiosis Marked By Decreased Butyrogenic Potential., Smita Ghare, Vaughn Bryant, Richa Singhal, Sabina Gautam, Chanakya Charan Tirumala, Andrea Reyes-Vega, Craig J. Mcclain, Ronald Cohen, Varand Govind, Robert L. Cook, Shirish Barve

Faculty and Staff Scholarship

Purpose: People living with HIV infection (PLWH) experience increasing risk for non-AIDS diseases including liver dysfunction and injury. Both HIV-infection and heavy alcohol drinking (HAD) are known to cause gut microbial dysbiosis and systemic inflammation that may potentially contribute to altered Gut-Liver axis. However, the specific pathogenic features associated with combinatorial harmful effects of alcohol and HIV infection on gut-liver interactions are not completely understood. This study evaluate the pathogenic changes in the Gut-Liver axis in PLWH with HAD.

Sodium Pyruvate Ameliorates Influenza A Virus Infection In Vitro And In Vivo, Jessica M. Reel

Graduate Theses/Dissertations

Pyruvate is produced in duplicate at the end of glycolysis in addition to ATP and NADH. Pyruvate is the metabolite of choice in most cells, whether obtained exogenously or endogenously. Recently we found that the addition of pyruvate’s conjugate base, sodium pyruvate, to cell culture media dampened the immune response to influenza A virus (IAV) infection in cultured innate immune cells. Thus, I decided to investigate the mechanism and potential for treatment of IAV. In vitro using bone marrow derived macrophages that were infected with IAV we found that adding sodium pyruvate to the media decreased immune signaling pathways through …

H1n1 Influenza Virus (Swine Flu): A Comprehensive Insight Into Escalating Catch-22 Scenarios, Muhammad Shahzaib, Ehsan Ul Haq

The University of Louisville Journal of Respiratory Infections

Introduction: Viruses have always been a major cause of various disastrous pandemics in mankind’s history. H1N1 became a threat when its original strain was first discovered back in the swine flu pandemic of 2009. It became highly catastrophic on a large scale because none of the therapeutic interventions and methodologies that were already present at the time were effective against the virus.

Methods: A vast amount of literature and research is available regarding H1N1 influenza from different reputable sources online. The data were gathered with the contrasting and relative situations of 1918 and 2009 pandemics in mind. The overall extracted …

Long-Term Dynamics Of The Kidney Disease Epidemic Among Hiv-Infected Individuals, Heather Gudaz, Henry A. Ogu, Elissa J. Schwartz

Spora: A Journal of Biomathematics

One of many risks facing HIV+ individuals is the development of kidney dysfunction and end stage kidney disease (ESKD). A differential equation-based mathematical model was developed to assess the impact of antiretroviral therapy on the progression to kidney disease and on reducing mortality due to kidney failure. Analytical and numerical predictions of long-term HIV+ ESKD prevalence show that therapy can lead to either extremely low levels of disease prevalence or increased prevalence, depending on drug efficacy levels and mechanisms of action. Maintenance of HIV+ ESKD prevalence below one individual is possible with sufficient efficacy (e.g., 99%) against the progression from …

The Intellectual Property Of Covid-19, Ana Santos Rutschman

All Faculty Scholarship

The response to COVID-19 is indissolubly tied to intellectual property. In an increasingly globalized world in which infectious disease pathogens travel faster and wider than before, the development of vaccines, treatments and other forms of medical technology has become an integral part of public health preparedness and response frameworks. The development of these technologies, and to a certain extent the allocation and distribution of resulting outputs, is informed by intellectual property regimes. These regimes influence the commitment of R&D resources, shape scientific collaborations and, in some cases, may condition the widespread availability of emerging technologies. As seen throughout this chapter, …

Covid-19 Employee Health Checks, Remote Work, And Disability Law, Elizabeth Pendo

All Faculty Scholarship

The Americans with Disabilities Act (ADA) prohibits discrimination against people with disabilities, about 61 million individuals in the U.S. The law’s protections in the workplace are especially important during COVID-19, which has worsened pre-existing disparities experienced by people with disabilities. The ADA also applies to new strategies to reduce the risk of COVID-19 infection in the workplace. This Chapter will focus on two strategies that impact individuals with and without disabilities – employee health screening, testing and vaccination policies, and new or expanded remote work programs.

Quercetin And Vitamin C: An Experimental, Synergistic Therapy For The Prevention And Treatment Of Sars-Cov-2 Related Disease (Covid-19), Ruben Manuel Luciano Colunga Biancatelli, Max Berrill, John D. Catravas, Paul Ellis Marik

Bioelectrics Publications

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) represents an emergent global threat which is straining worldwide healthcare capacity. As of May 27th, the disease caused by SARS-CoV-2 (COVID-19) has resulted in more than 340,000 deaths worldwide, with 100,000 deaths in the US alone. It is imperative to study and develop pharmacological treatments suitable for the prevention and treatment of COVID-19. Ascorbic acid is a crucial vitamin necessary for the correct functioning of the immune system. It plays a role in stress response and has shown promising results when administered to the critically ill. Quercetin is a well-known flavonoid whose antiviral properties …

The Case For Face Shields: Improving The Covid-19 Public Health Policy Toolkit, Timothy L. Wiemken, Ana Santos Rutschman, Robert Gatter

All Faculty Scholarship

As the United States battles the later stages of the first wave of COVID-19 and faces the prospect of future waves, it is time to consider the practical utility of face shields as an alternative or complement to face masks in the policy guidance. Without face shields specifically noted in national guidance, many areas may be reluctant to allow their use as an alternative to cloth face masks, even with sufficient modification.

In this piece, we discuss the benefits of face shields as a substitute to face masks in the context of public health policy. We further discuss the implications …

Why The Government Shouldn't Pay People To Get Vaccinated Against Covid-19, Ana Santos Rutschman

All Faculty Scholarship

As several pharmaceutical companies approach the Food and Drug Administration (FDA) seeking authorization to bring COVID-19 vaccines to market, concerns about vaccine mistrust cloud the prospects of imminent vaccination efforts across the globe. These concerns have prompted some commentators to suggest that governments may nudge vaccine uptake by paying people to get vaccinated against COVID-19. This post argues that, even if potentially viable, this idea is undesirable against the backdrop of a pandemic marked by the intertwined phenomena of health misinformation and mistrust in public health authorities. Even beyond the context of COVID-19, paying for vaccination is likely to remain …

Comments On The Preliminary Framework For Equitable Allocation Of Covid-19 Vaccine, Ana Santos Rutschman, Julia Barnes-Weise, Robert Gatter, Timothy L. Wiemken

All Faculty Scholarship

On September 1, 2020 the National Academies released a draft framework for Equitable Allocation of a COVID-19 Vaccine. In this response, we analyze the proposed framework and highlight several areas.

Among the proposed changes, we highlight the need for the following interventions. The final framework for distribution of COVID-19 vaccines should give a higher priority to populations made most vulnerable by the social determinants of health. It should incorporate more geography-based approaches in at least some of the four proposed phases of vaccine distribution. It should address the possibility of a vaccine being made available through an emergency use authorization …

Elucidating Immune Signaling Of Influenza A Virus And Aspergillus Fumigatus Co-Infections Through Pioneered Model Development, Meagan Danyelle Rippee-Brooks

Graduate Theses/Dissertations

Bacterial co-infections with influenza A virus (IAV) are extremely serious and life-threatening. However, there exists limited understanding about the importance of fungal infections with IAV. Clinical case reports indicate that fungal co-infections do occur and suggest the IAV pandemic of 2009 had a propensity to predispose patients to secondary fungal infections more than previous IAV strains. IAV-fungal co-infections are marked by high mortality rates of 47 to 61% in previously healthy individuals between the ages of 20 and 60. Yet, the variables involved in this co-infection remain undetermined. I achieved effective recapitulation of this co-infection using a C57Bl/6 murine (mouse) …

Environmental Sampling Techniques For Herd-Level Surveillance Of Bovine Viral Diarrhea Virus, Jaden Carlson

School of Veterinary and Biomedical Sciences: Dissertations, Theses, and Student Research

Control of Bovine Viral Diarrhea Virus (BVDV) relies on resource-intensive individual animal sampling to detect and remove persistently infected (PI) cattle. Herd-level surveillance tools would be useful for herds with unknown BVDV status and for monitoring herds with BVDV-free status. The overall objective of this thesis is to explore the viability of BVDV surveillance at a herd-level using samples collected without handling individual animals. The first objective was to determine the feasibility of using stable flies as a sampling tool to detect BVDV. The second objective was to determine the feasibility of using drinking water to detect BVDV. To accomplish …