Immunology and Infectious Disease Commons^™

Therapy With A Severe Acute Respiratory Syndrome-Associated Coronavirus-Neutralizing Human Monoclonal Antibody Reduces Disease Severity And Viral Burden In Golden Syrian Hamsters, Anjeanette Roberts, William Thomas, Jeannette Guarner, Elaine Lamirande, Gregory Babcock, Thomas Greenough, Leatrice Vogel, Norman Hayes, John Sullivan, Sherif Zaki, Kanta Subbarao, Donna Ambrosino

William D Thomas Jr

BACKGROUND: Immunotherapy with monoclonal antibodies (MAbs) offers safe interventions for the prevention of infection in patients after organ transplantation and for the treatment of cancers and autoimmune diseases. MAb 201 is a severe acute respiratory syndrome-associated coronavirus (SARS-CoV)-specific MAb that prevents establishment of viral replication in vitro and prevents viral replication in vivo when administered prophylactically. The efficacy of MAb 201 in the treatment of SARS was evaluated in golden Syrian hamsters, an animal model that supports SARS-CoV replication to high levels and displays severe pathological changes associated with infection, including pneumonitis and pulmonary consolidation. METHODS: Golden Syrian hamsters that …

A Supramolecular Strategy To Assemble Multifunctional Viral Nanoparticles, Limin Chen, Xia Zhao, Yuan Lin, Yubin Huang, Qian Wang

Faculty Publications

Using a one-pot approach driven by the supramolecular interaction between β-cyclodextrin and adamantyl moieties, multifunctional viral nanoparticles can be facilely formulated for biomedical applications.

Elucidating The Role Of Cathepsin B In The Lifecycle Of Influenza A Virus, Macon D. Coleman

Electronic Thesis and Dissertation Repository

Influenza virus type A (IVA) is the etiologic agent responsible for the febrile respiratory illness referred to as the flu. Seasonal and occasionally pandemic IVA-associated illness is a significant cause of morbidity and mortality worldwide, and presents a significant burden to the healthcare system. Our previous work showed that the propagation of IVA required the lysosomal protease cathepsin B (CTSB), though the mechanism behind this dependency was not elucidated. This study further examined the role of CTSB by using CTSB-deficient (CTSB^-/-) macrophages and the CTSB-specific chemical inhibitor CA-074 Me (CaMe) in human lung epithelial cells. CTSB^-/- and …

Modeling Leafhopper Populations And Their Role In Transmitting Plant Diseases., Ji Ruan

Electronic Thesis and Dissertation Repository

This M.Sc. thesis focuses on the interactions between crops and leafhoppers.

Firstly, a general delay differential equations system is proposed, based on the infection age structure, to investigate disease dynamics when disease latencies are considered. To further the understanding on the subject, a specific model is then introduced. The basic reproduction numbers $\cR_0$ and $\cR_1$ are identified and their threshold properties are discussed. When $\cR_0 < 1$, the insect-free equilibrium is globally asymptotically stable. When $\cR_0 > 1$ and $\cR_1 < 1$, the disease-free equilibrium exists and is locally asymptotically stable. When $\cR_1>1$, the disease will persist.

Secondly, we derive another general delay differential equations system to examine how different life stages of leafhoppers affect crops. The basic reproduction numbers $\cR_0$ is determined: when …

Mechanisms Contributing To The Emergence Of Ranavirus In Ectothermic Vertebrate Communities, Roberto M. Brenes

Doctoral Dissertations

Ranaviruses have been linked to amphibian die-off events in ectothermic vertebrates worldwide. Differences in susceptibility and capacity of transmission among and within classes are poorly understood. My goal was to determine possible mechanisms influencing susceptibility to ranavirus infection in amphibian species and other aquatic vertebrate taxa, as well as the capacity of transmission between classes and the effects of amphibian community composition on ranavirus transmission. I tested 16 amphibian species from USA, Europe, and the pet trade, expanding an existing database developed by the Center for Wildlife Health to 35 amphibian species from 9 families. I also tested the susceptibility …

Osmotic Stress, Not Aldose Reductase Activity, Directly Induces Growth Factors And Mapk Signaling Changes During Sugar Cataract Formation, Peng Zhang, Kuiyi Xing, James Randazzo, Karen Blessing, Marjorie F. Lou, Peter Kador

School of Veterinary and Biomedical Sciences: Faculty Publications

In sugar cataract formation in rats, aldose reductase (AR) actitvity is not only linked to lenticular sorbitol (diabetic) or galactitol (galactosemic) formation but also to signal transduction changes, cytotoxic signals and activation of apoptosis. Using both in vitro and in vivo techniques, the interrelationship between AR activity, polyol (sorbitol and galactitol) formation, osmotic stress, growth factor induction, and cell signaling changes have been investigated. For in vitro studies, lenses from Sprague Dawley rats were cultured for up to 48 hrs in TC-199-bicarbonate media containing either 30 mM fructose (control), or 30 mM glucose or galctose with/without the aldose reductase inhibitors …

Expert–Novice Differences In Mental Models Of Viruses, Vaccines, And The Causes Of Infectious Disease, Benjamin D. Jee, David H. Uttal, Amy N. Spiegel, Judy Diamond

World of Viruses

Humans are exposed to viruses everywhere they live, play, and work. Yet people’s beliefs about viruses may be confused or inaccurate, potentially impairing their understanding of scientific information. This study used semi-structured interviews to examine people’s beliefs about viruses, vaccines, and the causes of infectious disease. We compared people at different levels of science expertise: middle school students, teachers, and professional virologists. The virologists described more entities involved in microbiological processes, how these entities behaved, and why. Quantitative and qualitative analyses revealed distinctions in the cognitive organization of several concepts, including infection and vaccination. For example, some students and teachers …

Microsporidia Spore Adherence And Host Cell Infection In Vitro, Cory A. Leonard

Electronic Theses and Dissertations

Microsporidia infect invertebrate and vertebrate animals. Human pathogenic microsporidia are associated with severe disease in immunocompromised individuals, and mostly asymptomatic infection in the immunocompetent. Treatment options for microsporidiosis are limited, incompletely effective, and associated with toxicity. Furthermore, microsporidia infection of healthy individuals is poorly understood, and the consequences of asymptomatic infection have not been determined. Little is known about the molecular mechanisms of microsporidia infection, but such information is essential for the development of new therapies. Spores adhere to host cell surfaces in vitro. Our laboratory has focused on determining specific host cell and microsporidia spore surface participants in spore …

Coccidia Of Gerbils From Mongolia, Ethan T. Jensen

School of Biological Sciences: Dissertations, Theses, and Student Research

In this study, gerbils collected in the Mongolia over the summers of 2009-2012 were examined for coccidia. In total, 171 gerbils of three species from 22 localities were examined for coccidia. Coccidian oocysts were identified from 21 gerbils, but those found in 1 of those gerbils were probably pseudoparasites of the host from which they were recovered. From the remaining 20 gerbils, 7 morphotypes of Eimeria and 1 morphotype of Isospora were identified. Four of the 7 morphotypes of Eimeria were attributed to new species which were described in this study. In addition, 10 previously described species of Eimeria were …

Prevalence And Transmission Potential Of Borrelia Burgdorferi In Three Species Of Wildcaught Plestiodon Spp. Skinks Of The Southeastern United States, Teresa Dianne Moody

Masters Theses

In the southeastern United States, blue-tailed skinks (Plestiodon spp.) are important hosts for Ixodes scapularis ticks, the principal vector of Lyme disease (LD) in this region. Skinks and other southeastern lizards are not thought to be reservoir competent for Borrelia burgdorferi sensu stricto (Bbss), the etiological agent of LD in the United States. . Lizard-feeding by southeastern I. scapularis may tend to suppress sylvatic cycles of B. burgdorferi, and thus may be an important reason why LD case rates in the Southeast are much lower than in the Northeast and upper Midwest. Nevertheless, some skinks …

Role Of Msa In Immune Evasion, Persistence, And Protease Regulation In The Human Pathogenic Strains Of Staphylococcus Aureus, Maria Deepa Basco

Dissertations

Opportunistic pathogens like Staphylococcus aureus on entering the host can stay colonized at the foci of infection or evade the immune system to disseminate to other sites. In this study we investigated the regulatory influence of the modulator of sarA (msa) on immune evasion and host persistence, employing the hospital-acquired strain S. aureus UAMS-1 and community-acquired strain S. aureus USA300 LAC. In the murine sepsis model, mutation of the msa gene in LAC showed no change in dissemination of infection; however, in UAMS-1 a decrease in microbial load was observed in the lungs. Differential regulation by the msa gene was …

T-Cell Treatments For Solid And Hematological Tumors, Drew C. Deniger

Dissertations & Theses (Open Access)

Cell-based therapies have demonstrated potency and efficacy as cancer treatment modalities. T cells can be dichotomized by their T cell receptor (TCR) complexes where alpha/beta T cells (95% of T cells) and gamma/delta T cells (+T cells proliferated to clinically significant numbers and ROR1⁺ tumor cells were effectively targeted and killed by both ROR1-specific CAR⁺ T cell populations, although ROR1RCD137 were superior to ROR1RCD28 in clearance of leukemia xenografts in vivo. The second specific aim focused on generating bi-specific CD19-specific CAR⁺ gamma/delta T cells with polyclonal TCRgamma/delta repertoire on CD19⁺ artificial antigen presenting cells (aAPC). …

Trends In Borrelia Spp. Prevalence In Ixodes Spp. Ticks From The Southeastern Coastal United States, Lauren Paul Maestas

Masters Theses

The Lyme borreliosis (LB) cycle, involving Ixodes scapularis and Borrelia burgdorferi sensu stricto (Bbss), is well documented in the northeastern US, where LB is becoming increasingly prevalent. In coastal North Carolina, I. affinis has been shown to have a higher incidence of Bbss than I. scapularis. My objectives were, to assess changes in prevalence of Bbss in Ixodes spp. along a transect from Virginia to Florida, and to assess the value of dogs and mesomammals as sentinels for spread of Borrelia burgdorferi sensu lato.

Ixodes spp. were collected at sites from 37.4^o N to 30.0^{o …}

Association Study Of Common Genetic Variants And Hiv- 1 Acquisition In 6,300 Infected Cases And 7,200 Controls, Paul J. Mclaren, Cedric Coulonges, Stephan Ripke, Leonard H. Van Den Berg, Susan Buchbinder, Mary Carrington, Andrea Cossarizza, Judith Dalmau, Steven G. Deeks, Olivier Delaneau, Andrea De Luca, James J. Goedert, David W. Haas, Joshua T. Herbeck, Sekar Kathiresan, Gregory D. Kirk, Olivier Lambotte, Ma Luo, Simon Mallal, Danielle Van Manen, Javier Martinez-Picado, Florencia Pereyra, Francis A. Plummer, Guido Poli, Ying Qi, Pierre Rucart, Manj S. Sandhu, Patrick R. Shea, Hanneke Schuitemaker, Ioannis Theodorou, Fredrik Vannberg, Jan Veldink, Bruce D. Walker, Amy C. Weintrob, Cheryl Winkler, Steven M. Wolinsky, Amalio Telenti, David B. Goldstein, Paul I. W. De Bakker, Jean-Francois Zagury, Jacques Fellay

Biology Faculty Articles

Multiple genome-wide association studies (GWAS) have been performed in HIV-1 infected individuals, identifying common genetic influences on viral control and disease course. Similarly, common genetic correlates of acquisition of HIV-1 after exposure have been interrogated using GWAS, although in generally small samples. Under the auspices of the International Collaboration for the Genomics of HIV, we have combined the genome-wide single nucleotide polymorphism (SNP) data collected by 25 cohorts, studies, or institutions on HIV-1 infected individuals and compared them to carefully matched population-level data sets (a list of all collaborators appears in Note S1 in Text S1). After imputation using the …

P2x4 Assembles With P2x7 And Pannexin-1 In Gingival Epithelial Cells And Modulates Reactive Oxygen Species Production And Inflammasome Activation, Shu-Chen Hung, Chul Hee Choi, Najwane Said-Sadier, Larry Johnson, Kalina Rosenova Atanasova, Hanen Sellami, Özlem Yilmaz, David M. Ojcius

All Dugoni School of Dentistry Faculty Articles

We have previously reported that Porphyromonas gingivalis infection of gingival epithelial cells (GEC) requires an exogenous danger signal such as ATP to activate an inflammasome and caspase-1, thereby inducing secretion of interleukin (IL)-1β. Stimulation with extracellular ATP also stimulates production of reactive oxygen species (ROS) in GEC. However, the mechanism by which ROS is generated in response to ATP, and the role that different purinergic receptors may play in inflammasome activation, is still unclear. In this study, we revealed that the purinergic receptor P2X₄ is assembled with the receptor P2X₇ and its associated pore, pannexin-1. ATP induces ROS …

Alcohol Facilitates Hcv Rna Replication Via Up-Regulation Of Mir-122 Expression And Inhibition Of Cyclin G1 In Human Hepatoma Cells, Wei Hou, Terence Bukong, Karen Kodys, Gyongyi Szabo

Gyongyi Szabo

BACKGROUND: Clinical studies demonstrate synergistic liver damage by alcohol and hepatitis C virus (HCV); however, the mechanisms by which alcohol promotes HCV infection remain obscure. The liver-specific microRNA-122 (miR-122) regulates HCV replication and expression of host genes, including Cyclin G1. Here, we hypothesized that alcohol regulates miR-122 expression and thereby modulates HCV RNA replication. METHODS: The J6/JFH/Huh-7.5 model of HCV infection was used in this study. Real-time quantitative polymerase chain reaction, Western blotting, electrophoretic mobility shift assay, and confocal microscopy were used for experimental analysis. RESULTS: We found that acute alcohol exposure (25 mM) significantly increased intracellular HCV RNA as …

Structural And Thermodynamic Basis Of Amprenavir/Darunavir And Atazanavir Resistance In Hiv-1 Protease With Mutations At Residue 50, Seema Mittal, Rajintha Bandaranayake, Nancy King, Moses Prabu-Jeyabalan, Madhavi Nalam, Ellen Nalivaika, Nese Yilmaz, Celia Schiffer

Celia A. Schiffer

Drug resistance occurs through a series of subtle changes that maintain substrate recognition but no longer permit inhibitor binding. In HIV-1 protease, mutations at I50 are associated with such subtle changes that confer differential resistance to specific inhibitors. Residue I50 is located at the protease flap tips, closing the active site upon ligand binding. Under selective drug pressure, I50V/L substitutions emerge in patients, compromising drug susceptibility and leading to treatment failure. The I50V substitution is often associated with amprenavir (APV) and darunavir (DRV) resistance, while the I50L substitution is observed in patients failing atazanavir (ATV) therapy. To explain how APV, …

The Role Of Α5gaba(A) Receptors In Brain Inflammation, Jason K. Wong

Electronic Thesis and Dissertation Repository

Microglia critically regulate brain inflammation. GABA_A receptors that contain the α5-subunit (α5GABA_A) exhibit high sensitivity to GABA and confer tonic activity. Moreover, α5GABA­_A receptors have been associated with brain inflammation. This study investigates the role of α5GABA_A receptors in microglial activation. Immunohistochemistry revealed that in response to intraperitoneal lipopolysaccharide (LPS), α5-subunit null mice exhibited significantly higher expression of IL-1β in hippocampal microglia. Neuronal-glial co-cultures treated with α5GABA­_A receptor inverse agonist L655,708 drastically increased microglial IL-1β expression. Surprisingly, ELISA of media from L655,708-treated co-cultures revealed a considerably lower concentration of IL-1β. Treating cultured primary astrocytes …

Characterization Of The Gut Microbiota And Colitogenic Bacterial Species In Core 1 O-Glycans Deficient Mice, Maria E. Perez-Munoz

Department of Food Science and Technology: Dissertations, Theses, and Student Research

Mucus is one important component of the intestinal mucosal barrier, and loss of its functionality is associated with colitis in humans and mice. Mice deficient in core 1 O-glycans (TM-IEC C1galt1^-/-) display a thinner mucus layer upon mutation of the glycosyltransferase enzyme (C1GALT1) responsible for core 1 O-glycans attachment, thus constituting an experimental model for human Ulcerative Colitis (UC). Under conventional conditions, these mice experience spontaneous inflammation of the colon. However, the exact role of the microbiota in colitis development in these mice has not been systematically investigated.

Aimed to gain insights into the role of …

Heterogeneous Nuclear Ribonucleoprotein K Supports Vesicular Stomatitis Virus Replication By Regulating Cell Survival And Cellular Gene Expression, Phat X. Dinh, Anshuman Das, Rodrigo Franco, Asit K. Pattnaik

School of Veterinary and Biomedical Sciences: Faculty Publications

The heterogeneous nuclear ribonucleoprotein K (hnRNP K) is a member of the family of hnRNPs and was recently shown in a genome-wide small interfering RNA (siRNA) screen to support vesicular stomatitis virus (VSV) growth. To decipher the role of hnRNP K in VSV infection, we conducted studies which suggest that the protein is required for VSV spreading. Virus binding to cells, entry, and nucleocapsid uncoating steps were not adversely affected in the absence of hnRNP K, whereas viral genome transcription and replication were reduced slightly. These results indicate that hnRNP K is likely involved in virus assembly and/or release from …