Medicine and Health Sciences Commons^™

Examination Of Antiviral Resistance In Venezuelan Equine Encephalitis Virus, Jasper Lee

Theses and Dissertations (ETD)

Venezuelan equine encephalitis virus (VEEV) is a New World Alphavirus that causes Venezuelan equine encephalitis (VEE), which is characterized by a febrile illness that can progress to neurological disease and death. While no major outbreaks of VEE have occurred since 1995, VEEV is a virus of concern as, in addition to its spread through mosquitos, it can be aerosolized and used as a bioweapon. Unfortunately, there are currently no FDA-approved vaccines or antivirals against VEEV. Efforts have been made to discover small molecules with an inhibitory effect on VEEV, but the potential for emergence of antiviral resistance to these compounds …

Ecology Of Hantaviruses In Rodent Reservoirs And Their Early Innate Immune Responses In Human Model Systems, Evan Peter Williams

Theses and Dissertations (ETD)

The spillover of zoonotic RNA viruses is responsible for a great deal of the disease outbreaks in human populations. These spillover events are set to continue due to anthropogenic and environmental changes that impact the distribution of these viruses. The viruses in the family Hantaviridae are classified as one of these emerging zoonotic RNA viruses. The spillover of the viruses in this family are responsible for two severe human diseases, hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). These viruses are distributed across the globe and are responsible for a large number of human disease cases with …

Responding To The Pandemic: A Multicountry Study On Social-Political Factors And Health Outcomes Of Covid-19, Lan Yao

Theses and Dissertations (ETD)

Introduction. Coronavirus Disease 2019 (COVID-19) poses a major global threat to human beings, which has caused devastating consequences of population health, political, and economic crises in many countries. This dissertation was composed of three research activities to study the following aims: (1) review the existing literature focusing on political factors and health outcomes of COVID-19; (2) assess the relationship between democracy and case fatality rate of COVID-19 by controlling for the effect of age, comorbidity, health expenditure, healthcare workforce, and population density; and (3) identify the trajectory pattern cases peak days, deaths peak days, and peak periods.

Methods. We accessed …

Advancing Rna Virus Discovery And Biology With Whole Genome Sequencing, Mariah Katherine Taylor

Theses and Dissertations (ETD)

Two RNA virus families that pose a threat to human and animal health are Hantaviridae and Coronaviridae. These RNA viruses which originate in wildlife continue and will continue to cause disease, and hence, it is critical that scientific research define the mechanisms as to how these viruses spillover and adapt to new hosts to become endemic. One gap in our ability to define these mechanisms is the lack of whole genome sequences for many of these viruses. To address this specific gap, I developed a versatile amplicon-based whole-genome sequencing (WGS) approach to identify viral genomes of hantaviruses and severe acute …

Combating Hiv-1 By Targeting Drug Efflux Transporters On The Macrophage Reservoir, Ying Mu

Theses and Dissertations (ETD)

Introduction. HIV-1 eradication has not been achieved so far due to the existence of the cellular reservoir in which the virus can reside and replicate even under antiretroviral drug therapy (ART). Infected macrophages, which represent a long-term viral reservoir have been shown to lead to viral rebound independently. In response to the environmental stimuli, macrophages can be polarized into different phenotypes: the pro-inflammatory M1 and the anti-inflammatory M2. Tobacco smoking and alcohol drinking, which are prevalent among people who are living with HIV-1, have been shown to promote HIV-1 progression and decrease the efficacy of antiretroviral drugs. A commonly …

Dissecting Drivers Of Basal Immunity And Acute Responses To Viral Infection, Aisha Nadia Hegab Souquette

Theses and Dissertations (ETD)

Heterogeneity in the human immune system can lead to limited vaccine efficacy, poor response to therapeutics, increased susceptibility to immune mediated diseases, and differential outcome to infection. Studies to date have suggested a role for biological, environmental, and genetic factors in immune variation; however, they are often focused on a specific subset of the population (e.g. ancestral group, age range) which can exclude phenotypes unique to a diverse population and bias results. To address this gap, we have utilized samples from healthy or influenza virus infected subjects from 8 distinct populations in 5 countries to conduct an integrative analysis of …

Attenuation Of Interferon Responses In The Obese Host And Ramifications For Influenza Virus Evolution, Rebekah Reed Honce

Theses and Dissertations (ETD)

The most insidious pandemic of modern life does not arise from an infectious agent but rather from malnutrition. With its global incidence tripling over the past three decades, obesity is a major public health concern. Obesity’s rising prevalence has also illuminated its impact on communicable diseases. Following the 2009 H1N1 influenza A virus pandemic, obesity was identified as a risk factor for increased disease severity and mortality in infected individuals. Obesity causes a chronic state of meta-inflammation with systemic implications for immunity, including delayed antiviral responses to influenza virus infection, poor recovery, and impaired immunological memory. However, the majority of …

Tobacco/Hiv-1-Induced Myeloid Cell-Derived Extracellular Vesicles In Hiv-1 Pathogenesis, Sanjana Haque

Theses and Dissertations (ETD)

Introduction. Smoking, which is highly prevalent in people living with HIV/AIDS, has been shown to exacerbate HIV-1 replication, in part via cytochrome P450 (CYP)-induced oxidative stress. CYP enzymes metabolize cigarette smoke condensate (CSC), causing oxidative stress and cytotoxicity. Our previous studies have demonstrated that CSC and specific CSC constituents, benzo(a)pyrene and nicotine, potentially induce CYPs, resulting in higher oxidative stress and subsequent exacerbation of HIV-1 replication in monocytes and macrophages. However, the exact mechanism behind tobacco-induced, oxidative stress-mediated enhancement of HIV-1 replication is still poorly understood. Extracellular vesicles (EVs) have recently gained attention for their unique nature as intercellular messengers …

Role Of Dendritic Cells In Pathology Of Respiratory Syncytial Virus Infection In Neonates, Bishwas Shrestha

Theses and Dissertations (ETD)

Respiratory syncytial virus (RSV) is one of the leading causes of bronchiolitis in children. We have shown that neonatal mice respond to primary RSV infection with T helper type 2 (Th2) biased immune responses, which are enhanced following reinfection. Dendritic cells (DCs) including myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) play important roles in driving host responses to RSV infection. mDCs present antigens to help Th cells differentiate, and pDCs protect against viral infection through type I interferons (IFNs). Despite data demonstrating importance of mDCs and pDCs in protection against RSV, it has not been studied in an age appropriate …

Assessment Of The Zoonotic Potential Of A Novel Bovine Influenza Virus, Laura Evelyn Eckard

Theses and Dissertations (ETD)

A novel orthomyxovirus was recently identified from pigs, with subsequent work suggesting the natural reservoir being bovine populations. The virus had genome characteristics most similar to influenza C viruses (ICV) but, due to the extent of sequence divergence, was proposed as a new genus, influenza D virus (IDV). Current literature on IDV has largely focused on the agricultural significance of the virus and provided evidence for the agricultural impact via observation of widespread prevalence and pathology in laboratory infected cattle. However, only one study, which identified 1.3% seroprevalence in a small cohort, has addressed the zoonotic potential of IDV to …

Anal Cancer Risk Factor Management Practices And The Barriers And Facilitators Of Addressing Anal Health In The Hiv Primary Care Setting, Crystal Martin Walker

Theses and Dissertations (ETD)

Background: The incidence of anal cancer is only 1-2 per 100,000 people in the general population, but in people living with HIV and AIDS (PLWHA), the incidence is far greater by about 80 times. This is a striking disproportion, and it is vital for the healthcare provider and healthcare system to become more attentive to the risk of anal cancer in high-risk populations such as PLWHA. There are a number of modifiable risk factors for anal cancer in PLWHA such as smoking, non-adherence to antiretroviral therapy (ART), and risky sexual behaviors. The HIV primary care provider (HIV PCP) plays a …

A Novel Mechanism Of Enhanced Susceptibility To Bacterial Pneumonia In Influenza-Infected Hosts, Hazem Elsayed Ghoneim

Theses and Dissertations (ETD)

Viruses such as influenza suppress host immune function by a variety of methods. This may result in a significant morbidity through several pathways, including facilitation of secondary bacterial pneumonia from pathogens such as Streptococcus pneumoniae. Lungresident alveolar macrophages (AMs) act as the first line of innate cellular immunity against respiratory bacterial pathogens, including pneumococcus. Therefore, they represent an attractive target for study Before investigating the impact of influenza infection on resident AMs, we first characterized different subsets of lung-resident macrophages in naïve mice using a novel in vivo labeling approach in conjunction with multicolor flow cytometric analysis and confocal microscopic …

The Molecular Basis Of Fitness And Transmissibility Of Neuraminidase Inhibitor Resistant Influenza A Viruses, Susu Duan

Theses and Dissertations (ETD)

Neuraminidase (NA) inhibitors including oral oseltamivir and inhaled zanamivir are among the first line of defense against influenza virus infection. Development of resistance to NA inhibitors is a huge drawback for limited options for the control of influenza. During the first decade of NA inhibitor use, the detection rates of resistance to both NA inhibitors had remained low in circulating influenza viruses. However, the 2008~2009 season was marked by a radical increase of prevalence of oseltamvir resistance from <1% to >90% in worldwide surveillance in less than a year. The resistance was solely linked to NA H275Y variants of seasonal H1N1 viruses, …

Impact Of Adjuvants On The Antibody Responses To Pre-Pandemic H5n1 Influenza Vaccines, Ali Hassan Ellebedy

Theses and Dissertations (ETD)

Human influenza pandemics occur when influenza viruses to which the population has little or no immunity emerge and acquire the ability to transmit among humans. Since their emergence in 1996, human infections with highly pathogenic avian influenza A (H5N1) viruses presented a serious public health challenge. Additionally, H5N1 viruses caused significant agricultural and economic losses in the communities it has affected. Human infections with these viruses are rare but when they occur, these infections are highly fatal. A greater public health concern stems from the rapid evolution displayed by these viruses so far, which in turn might result in viruses …

Glycan Shielding Of The Influenza Virus Hemagglutinin Elicits Evasion Of The Adaptive Immune Response And T-Cell-Driven Pathology, Keith C. Wanzeck

Theses and Dissertations (ETD)

Three separate influenza pandemics have emerged in the human population since 1918, each characterized by viruses that lack N-linked glycosylation sites on the globular head of the hemagglutinin protein. In contrast, recent non-pandemic isolates have acquired such sites. Here we constructed isogenic viruses containing differing numbers of additional N-linked glycosylation sites to assess the impact on the host immune response. These studies show that mice infected with a glycosylated virus remain susceptible to challenge with a non-glycosylated virus, glycosylated viruses elicit an inferior immune response, and in this context T-cell pathology and death may occur. We conclude from these data …

Impact Of Parent’S Hiv Status On Their Uninfected Child—A Comparative Analysis Of The Child’S Healthcare Utilization, Access And Health Outcomes, Arijit Ganguli

Theses and Dissertations (ETD)

With the advent of effective antiretroviral medication and increased expectancy of life span among HIV-infected individuals has lead to an increase in the at-risk population of uninfected children living with their HIV-infected parent(s). The purpose of this study was to investigate the impact of parent’s HIV status on their child’s access to healthcare resources, healthcare utilization and health outcomes.

This was a cross-sectional study in which the information on the children of HIV seropositive parent(s) was collected through a face-to-face interview of the HIV-infected parents having children currently residing with them. The comparative group comprising of children of HIV seronegative …

Pandemic Potential Of Reassortant Swine Influenza A Viruses, Christy Brockwell Staats

Theses and Dissertations (ETD)

Influenza A viruses are capable of causing disease in several species, including birds, humans and swine. Host specificity of the viruses is not absolute, and is influenced by a range of factors. Swine play a pivotal role in the interspecies transmission of influenza A viruses, as they are susceptible to infection with both human and avian strains and have been implicated as a “mixing vessel” for the reassortment of influenza A viruses from different species. The reassortment of influenza A viruses of human and avian origin led to human influenza pandemics in 1957 and 1968.

The dynamics of swine influenza …

Contribution Of The Membrane-Proximal Region Of The Vesicular Stomatitis Virus Glycoprotein To Host Cell Entry And Membrane Fusion, Elizabeth Lane Matheny

Theses and Dissertations (ETD)

Vesicular stomatitis virus (VSV) is an enveloped, nonsegmented, negative-sense, RNA virus belonging to the Rhabdoviridae family. VSV is considered the prototypic Rhabdovirus due to its simple genetic organization, broad host cell tropism, and ability to be easily grown in cell culture. Therefore, VSV has been used as the prototype to study viral entry, transcription, replication, and assembly. Viral entry, a critical step in the lifecycle of the virus, is mediated by the outer surface protein, G and will be the focus of this dissertation.

We hypothesize that the highly conserved residues in the membrane-proximal region of VSV G protein are …

Regulation Of The Human Parainfluenza Virus (Hpiv3) Fusion Protein, Amanda Ruth Chapman

Theses and Dissertations (ETD)

Paramyxoviruses include a number of important human pathogens, including measles virus, mumps virus, and the human parainfluenza viruses (hPIV) 1-4, as well as several animal pathogens, such as Sendai virus, Nipah virus and Hendra virus. The creation of effective drugs and vaccines against this family of viruses would play an important role in decreasing the prevalence of these viruses and contributing to the health of both humans and animals worldwide. The purpose of this work was to determine how the fusion (F) protein is regulated with a focus on the heptad repeat B (HRB) region of the F protein located …

Predictors Of Depressive And Anxiety Symptoms Among African American Hiv-Positive Women, Nina Katherine Sublette

Theses and Dissertations (ETD)

This descriptive correlation study had four purposes: describe depressive and anxiety symptom levels in pregnant and non-pregnant African American (AA) HIV-positive women, examine the association between underlying vulnerabilities and depressive symptoms in HIV-positive AA women, determine the association between underlying vulnerabilities and anxiety symptoms in AA HIV-positive women, and determine the predictors of depressive and anxiety symptoms among African American HIV-positive women. A convenience sample of 80 African American HIV-positive women was recruited from university-based obstetrics/-gynecology and infectious disease practices in a large metropolitan city in the Mid-South. Depressive symptoms were measured with the Center for Epidemiologic Studies Depression Scale …