Immunology and Infectious Disease Commons^™

Epigenetic Modifiers To Augment The Immunogenicity Of Chronic Lymphocytic Leukemia, Jason A. Dubovsky

USF Tampa Graduate Theses and Dissertations

Cancer cells employ a litany of immunosuppressive and immunevasive strategies to avoid detection and elimination by the various arms of the innate and adaptive immune system. Many hematologic and solid tumors progressively develop a specialized microenvironment which promotes tissue restructuring inflammation while masking the immune signature of the tumor cells themselves. Chronic lymphocytic leukemia, a malignancy of mature B lymphocytes must constantly balance on the precipice of immune recognition. A mature antigen presenting cell themselves, CLL clonal growth is dependent on the very interactions which, if effective, could potentially lead to their demise. To circumvent this, CLL clones set up …

Worms, Nematoda, Scott Lyell Gardner

Scott L. Gardner Publications

Nematodes are the most speciose phylum of metazoa on earth. Not only do they occur in huge numbers as parasites of all known animal groups, but also they are found in the soils, as parasites of plants, and in large numbers in the most extreme environments, from the Antarctic dry valleys to the benthos of the ocean. They are extremely variable in their morphological characteristics, with each group showing morphological adapta­tions to the environment that they inhabit. Soil-dwelling forms are extremely small; many marine species have long and complex setae; and parasitic species man­ifest amazingly great reproductive potential and large …

Influence Of Therapeutic Ceftiofur Treatments Of Feedlot Cattle On Fecal And Hide Prevalences Of Commensal Escherichia Coli Resistant To Expanded-Spectrum Cephalosporins, And Molecular Characterization Of Resistant Isolates, John W. Schmidt, Dee Griffin, Larry A. Kuehn, Dayna M. Brichta-Harhay

School of Veterinary and Biomedical Sciences: Faculty Publications

In the United States, the bla_CMY-2 gene contained within incompatibility type A/C (IncA/C) plasmids is frequently identified in extended-spectrum-cephalosporin-resistant (ESC^r) Escherichia coli strains from both human and cattle sources. Concerns have been raised that therapeutic use of ceftiofur in cattle may increase the prevalence of ESC^r E. coli. We report that herd ESC^r E. coli fecal and hide prevalences throughout the residency of cattle at a feedlot, including during the period of greatest ceftiofur use at the feedlot, were either not significantly different (P≥0.05) or significantly less (Pr E. coli shedding that follows ceftiofur …

Complete Closed Genome Sequences Of Mannheimia Haemolytica Serotypes A1 And A6, Isolated From Cattle, Gregory P. Harhay, Sergey Koren, Adam M. Phillippy, D. Scott Mcvey, Jennifer Kuszak, Michael L. Clawson, Dayna M. Harhay, Michael P. Heaton, Carol G. Chitko-Mckown, Timothy P. L. Smith

School of Veterinary and Biomedical Sciences: Faculty Publications

Mannheimia haemolytica is a respiratory pathogen affecting cattle and related ruminants worldwide. M. haemolytica is commonly associated with bovine respiratory disease complex (BRDC), a polymicrobial multifactorial disease.Wepresent the first two complete closed genome sequences of this species, determined using an automated assembly pipeline requiring no manual finishing.

Development And Evaluation Of A Replicon Particle Vaccine Expressing The E2 Glycoprotein Of Bovine Viral Diarrhea Virus (Bvdv) In Cattle, John Dustin Loy, Jill Gander, Mark Mogler, Ryan Vander Veen, Julia Ridpath, Delbert Hank Harris, Kurt Kamrud

School of Veterinary and Biomedical Sciences: Faculty Publications

Background: Bovine viral diarrhea virus is one of the most significant and costly viral pathogens of cattle worldwide. Alphavirus-derived replicon particles have been shown to be safe and highly effective vaccine vectors against a variety of human and veterinary pathogens. Replicon particles are non-propagating, DIVA compatible, and can induce both humoral and cell mediated immune responses. This is the first experiment to demonstrate that Alphavirus-based replicon particles can be utilized in a standard prime/boost vaccination strategy in calves against a commercially significant bovine pathogen.

Findings: Replicon particles that express bovine viral diarrhea virus sub-genotype 1b E2 glycoprotein were …

A Dysfunctional Tricarboxylic Acid Cycle Enhances Fitness Of Staphylococcus Epidermidis During Β-Lactam Stress, Vinai Chittenzham Thomas, Lauren Kinkhead, Ashley Janssen, Carolyn Schaeffer, Keith Woods, Jill Lindgren, Johnathan Peaster, Sujata Chaudhari, Marat Sadykov, Joselyn Jones, Sameh Mohamadi Abdelghani, Matthew Zimmerman, Kenneth W. Bayles, Greg Somerville, Paul Fey

School of Veterinary and Biomedical Sciences: Faculty Publications

A recent controversial hypothesis suggested that the bactericidal action of antibiotics is due to the generation of endogenous reactive oxygen species (ROS), a process requiring the citric acid cycle (tricarboxylic acid [TCA] cycle). To test this hypothesis, we assessed the ability of oxacillin to induce ROS production and cell death in Staphylococcus epidermidis strain 1457 and an isogenic citric acid cycle mutant. Our results confirm a contributory role for TCA-dependent ROS in enhancing susceptibility of S. epidermidis toward β-lactam antibiotics and also revealed a propensity for clinical isolates to accumulate TCA cycle dysfunctions presumably as a way to tolerate these …

Interferon Inducible Protein Ifi35 Negatively Regulates Rig-I Antiviral Signaling And Supports Vesicular Stomatitis Virus Replication, Anshuman Das, Phat X. Dinh, Debasis Panda, Asit K. Pattnaik

School of Veterinary and Biomedical Sciences: Faculty Publications

In a genome-wide siRNA screen, we recently identified the interferon (IFN) inducible protein 35 (IFI35, also known as IFP35) as a factor required for VSV infection. Studies reported here were conducted to further understand the role and requirement of IFI35 in VSV infection. Consistent with the siRNA screening data, we found that depletion of IFI35 led to reduced VSV replication at the level of viral gene expression. Although no direct interaction of IFI35 with the viral replication machinery was observed, we found that IFI35 negatively regulated the host innate immune response and rescued poly(I:C)-induced inhibition of VSV replication. Promoter-driven reporter …

Characterization Of A Serologic Marker Candidate For Development Of A Live-Attenuated Diva Vaccine Against Porcine Reproductive And Respiratory Syndrome Virus, Hiep Vu, Byungjoon Kwon, Marcelo De Lima, Asit K. Pattnaik, Fernando A. Osorio

School of Veterinary and Biomedical Sciences: Faculty Publications

DIVA (differentiating infected from vaccinated animals) vaccines have proven extremely useful for control and eradication of infectious diseases in livestock. We describe here the characterization of a serologic marker epitope, so-called epitope-M201, which can be a potential target for development of a live-attenuated DIVA vaccine against porcine reproductive and respiratory syndrome virus (PRRSV). Epitope-M201 is located at the carboxyl terminus (residues 161-174) of the viral M protein. The epitope is highly immunodominant and well-conserved among type-II PRRSV isolates. Rabbit polyclonal antibodies prepared against this epitope are non-neutralizing; thus, the epitope does not seem to contribute to the protective immunity against …

Trex1 Regulates Lysosomal Biogenesis And Interferon-Independent Activation Of Antiviral Genes, Maroof Hasan, James Koch, Dinesh Rakheja, Asit K. Pattnaik, James Brugarolas, Igor Dozmorov, Beth Levine, Edward K. Wakeland, Min Ae Lee-Kirsch, Nan Yan

School of Veterinary and Biomedical Sciences: Faculty Publications

Innate immune sensing of viral nucleic acids triggers type I interferon (IFN) production, which activates interferon-stimulated genes (ISGs) and directs a multifaceted antiviral response. ISGs can also be activated through IFN-independent pathways, although the precise mechanisms remain elusive. Here we found that the cytosolic exonuclease Trex1 regulates the activation of a subset of ISGs independently of IFN. Both Trex1−/− mouse and TREX1-mutant human cells express high levels of antiviral genes and are refractory to viral infections. The IFN-independent activation of antiviral genes in Trex1−/− cells requires STING, TBK1 and IRF3 and IRF7. We also found that Trex1-deficient cells display expanded …

Glutaredoxin-2 Is Required To Control Proton Leak Through Uncoupling Protein-3, Ryan J. Mailloux, Jian Ying Xuan, Brittany Beauchamp, Marjorie F. Lou, Mary-Ellen Harper

School of Veterinary and Biomedical Sciences: Faculty Publications

Glutathionylation has emerged as a key modification required for controlling protein function in response to changes in cell redox status. Recently, we showed that the glutathionylation state of uncoupling protein-3 (UCP3) modulates the leak of protons back into the mitochondrial matrix, thus controlling reactive oxygen species production. However, whether or not UCP3 glutathionylation is mediated enzymatically has remained unknown because previous work relied on the use of pharmacological agents, such as diamide, to alter the UCP3 glutathionylation state. Here, we demonstrate that glutaredoxin-2 (Grx2), a matrix oxidoreductase, is required to glutathionylate and inhibit UCP3. Analysis of bioenergetics in skeletal muscle …

Sequence-Optimized And Targeted Double-Stranded Rna As A Therapeutic Antiviral Treatment Against Infectious Myonecrosis Virus In Litopenaeus Vannamei, J. Dustin Loy, Duan S. Loy, Mark A. Mogler, Bruce Janke, Kurt Kamrud, D. L. Hank Harris, Lyric C. Bartholomay

School of Veterinary and Biomedical Sciences: Faculty Publications

Infectious myonecrosis virus (IMNV) is a significant and emerging pathogen that has a tremendous impact on the culture of the Pacific white shrimp Litopenaeus vannamei. IMNV first emerged in Brazil in 2002 and subsequently spread to Indonesia, causing large economic losses in both countries. No existing therapeutic treatments or effective interventions currently exist for IMNV. RNA interference (RNAi) is an effective technique for preventing viral disease in shrimp. Here, we describe the efficacy of a double-stranded RNA (dsRNA) applied as an antiviral therapeutic following virus challenge. The antiviral molecule is an optimized dsRNA construct that targets an IMNV sequence …

A New Species Of Metathelazia (Nematoda: Pneumospiruridae) From The Lungs Of A Nine-Banded Armadillo In Central Mexico = Especie Nueva De Metathelazia (Nematoda: Pneumospiruridae) De Los Pulmones De Un Armadillo Del Centro De México, F. Agustín Jiménez-Ruiz, Rogelio Rosas-Valdez, Scott Lyell Gardner

Harold W. Manter Laboratory of Parasitology: Faculty Publications

Twenty-four worms were collected from the bronchioles in both lungs of a male nine-banded armadillo Dasypus novemcinctus Linnaeus, 1758 captured in Teacalco, Morelos, Mexico. The worms, herein named Metathelazia mexicana n. sp., show a constriction in the esophagus at the level of the nerve ring; males of the species have 7 pairs of papillae, fewer than the other species in the genus. Metathelazia capsulata is the most similar species to Metathelazia mexicana; however, the latter has much shorter spicules. This is the fourth species in the genus known to occur in the New World.

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On The Morphology And Taxonomy Of Griphobilharzia Amoena Platt And Blair, 1991 (Schistosomatoidea), A Dioecious Digenetic Trematode Parasite Of The Freshwater Crocodile, Crocodylus Johnstoni, In Australia [Critical Comment], Thomas R. Platt, Eric P. Hoberg, Leslie A. Chisholm

Harold W. Manter Laboratory of Parasitology: Faculty Publications

Griphobilharzia amoena Platt and Blair, 1991 was originally described was originally described as a dioecious trematode, parasitic in the circulatory system of the Australian freshwater crocodile, Crocodylus johnstoni, with the female completely enclosed in a gynecophoric chamber of the male and the two worms orientated anti-parallel to each other. A recent publication questions the original description, arguing that G. amoena is monoecious and, as a consequence, the species was transferred to Vasotrema Stunkard, 1928 (Spirorchiidae) as Vasotrema amoena n. comb. We provide photomicrographic evidence that the original description of G. amoena is correct and that Griphobilharzia Platt and Blair, …

Dirofilariosis In The Americas: A More Virulent Dirofilaria Immitis?, Filipe Dantas-Torres, Domenico Otranto

Harold W. Manter Laboratory of Parasitology: Library Materials

Dirofilarioses are widespread diseases caused by filarioid nematodes (superfamily Filarioidea) of the genus Dirofilaria, which are transmitted by a plethora of mosquito species. The principal agent of canine dirofilariosis in the Americas is Dirofilaria immitis, which may also occasionally infest humans, resulting in pulmonary nodules that may be confounded with malignant lung tumours. Because human cases of dirofilariosis by D. immitis are relatively frequent in the Americas and rare in Europe and other eastern countries, where Dirofilaria repens is the main causative agent, the existence of a more virulent strain of D. immitis in the Americas …

The Molecular Basis Of Antibody Mediated Neutralization Of Hepatitis C Virus, Michelle Catherine Sabo

All Theses and Dissertations (ETDs)

Hepatitis C virus: HCV) is positive strand, blood-borne, hepatotropic RNA virus that causes chronic infection in ~170 million people worldwide and is the leading cause of liver transplantation in the United States. HCV entry and attachment is mediated by the envelope protein E2 through interaction with several cellular receptors including CD81, scavenger receptor B1: SRB-1), claudin-1, and occludin, although the exact mechanism by which these receptors facilitate infection remains unclear, largely due to the absence of a structural model of E2. The production of neutralizing antibodies against E2 is thought to be important for controlling HCV infection, likely by blocking …

Measuring Population Transmission Potential For Hiv: An Alternative Metric Of Transmission Risk In Men Who Have Sex With Men (Msm) In The Us, Colleen F. Kelley, Eli S. Rosenberg, Brandon M. O'Hara, Paula M. Frew, Travis Sanchez, John L. Peterson, Carlos Del Rio, Patrick S. Sullivan

Environmental & Global Health Faculty Research

Background Various metrics for HIV burden and treatment success [e.g. HIV prevalence, community viral load (CVL), population viral load (PVL), percent of HIV-positive persons with undetectable viral load] have important public health limitations for understanding disparities. Methods and Findings Using data from an ongoing HIV incidence cohort of black and white men who have sex with men (MSM), we propose a new metric to measure the prevalence of those at risk of transmitting HIV and illustrate its value. …See full text for complete abstract.

Cloning, Expression, And Characterization Of Ara H 3, A Major Peanut Allergen, Cathryn E. Garvey

LSU New Orleans Theses and Dissertations

Abstract There are eight foods that contribute to food allergies in the western world and peanut is the most common. Currently, there are no medical treatments that can cure an individual of food allergy, so avoidance of the allergic food is the only option. In the United States, there are three immunodominant allergic proteins accountable for patient sensitization to peanut, Arachis hypogea 1, 2, and 3 (Ara h 1, Ara h 2, Ara h 3). Therefore, research into why peanuts are more allergic than other foods that have homologous proteins is critical and may be obtained by studying the structural …

Molecular Characterization Of A Tetraspanin From The Human Liver Fluke, Opisthorchis Viverrini, Supawadee Piratae, Smarn Tesana, Malcolm K. Jones, Paul J. Brindley, Alex Loukas, Erica Lovas, Veerachai Eursitthichai, Banchob Sripa, Sirikanda Thanasuwan, Thewarach Laha

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background

The human liver fluke, Opisthorchis viverrini, is designated as a group 1 carcinogen, and is the major risk factor for cholangiocarcinoma in endemic countries throughout Southeast Asia. Proteins in the excretory-secretory products and tegumental surface membranes of the fluke have been proposed to play pivotal roles in parasite survival in the host, and subsequent pathogenesis. These macromolecules are therefore valid targets for the development of vaccines and new drugs to control the infection. Tetraspanins (TSP) are prominent components of the tegument of blood flukes where they are essential for tegument formation, are directly exposed to the immune system, …

Distinct Mechanisms Mediate Naïve And Memory Cd8 T-Cell Tolerance, Evan R. Jellison, Elizabeth G. Lingenheld, Li Zu, Lynn Puddington, Leo Lefrancois

UCHC Articles - Research

Peripheral tolerance to developmentally regulated antigens is necessary to sustain tissue homeostasis. We have now devised an inducible and reversible system that allows interrogation of T-cell tolerance induction in endogenous naïve and memory CD8 T cells. Our data show that peripheral CD8 T-cell tolerance can be preserved through two distinct mechanisms, antigen addiction leading to anergy for naïve T cells and ignorance for memory T cells. Induction of antigen in dendritic cells resulted in substantial expansion and maintenance of endogenous antigen-specific CD8 T cells. The self-reactive cells initially exhibited effector activity but eventually became unresponsive. Upon antigen removal, the antigen-specific …

Cues Used By The Black Fly, Simulium Annulus, For Attraction To The Common Loon (Gavia Immer), Meggin L. Weinandt, Michael W. Meyer, R. Mac Strand, Alec R. Lindsay Ph. D.

Faculty Works

The parasitic relationship between a black fly, Simulium annulus, and the common loon (Gavia immer) has been considered one of the most exclusive relationships between any host species and a black fly species. To test the host specificity of this blood-feeding insect, we made a series of bird decoy presentations to black flies on loon-inhabited lakes in northern Wisconsin, U.S.A. To examine the importance of chemical and visual cues for black fly detection of and attraction to hosts, we made decoy presentations with and without chemical cues. Flies attracted to the decoys were collected, identified to species, and quantified. Results …