Immunology and Infectious Disease Commons^™

Antagonistic Effects Of Cellular Poly(C) Binding Proteins On Vesicular Stomatitis Virus Gene Expression, Phat X. Dinh, Lalit Beura, Debasis Panda, Anshuman Das, Asit K. Pattnaik

School of Veterinary and Biomedical Sciences: Faculty Publications

Immunoprecipitation and subsequent mass spectrometry analysis of the cellular proteins from cells expressing the vesicular stomatitis virus (VSV) P protein identified the poly(C) binding protein 2 (PCBP2) as one of the P protein-interacting proteins. To investigate the role of PCBP2 in the viral life cycle, we examined the effects of depletion or overexpression of this protein on VSV growth. Small interfering RNA-mediated silencing of PCBP2 promoted VSV replication. Conversely, overexpression of PCBP2 in transfected cells suppressed VSV growth. Further studies revealed that PCBP2 negatively regulates overall viral mRNA accumulation and subsequent genome replication. Coimmunoprecipitation and immunofluorescence microscopic studies showed that …

Chemoprevention Of Familial Melanoma, Vidhya Hariharan

Dissertations (6 month embargo)

Bleaching agents 4-tertiary butyl phenol (4-TBP) and monobenzyl ether of hydroquinone (MBEH) have been known to cause occupational vitiligo This project answers whether agents 4-TBP and MBEH can be used for prophylactic treatment of familial melanoma by being specifically toxic to melanocytes and activating an immune response against distant pigment cells. Cytotoxic experiments reveal that similar to 4-TBP, MBEH induces specific melanocyte death. To compare death pathways initiated by 4-TBP and MBEH, classical apoptotic hallmarks were evaluated in treated melanocytes. MBEH induced cell death without activating the caspase cascade or DNA fragmentation, showing that the death pathway is non-apoptotic. Release …

Helminths Of Small Mammals (Erinaceomorpha, Soricomorpha, Chiroptera, Rodentia, And Lagomorpha) Of Mongolia, David S. Tinnin, Sumiya Ganzorig, Scott Lyell Gardner

Harold W. Manter Laboratory of Parasitology: Faculty Publications

Ninety-eight species of small mammal, excluding carnivores and ungulates, are currently recognized in the fauna of Mongolia. A list of species of helminths known to infect these species, both within Mongolia and across their range, is presented in an effort to aid in their study. A detailed bibliography of pertinent survey and related publications is provided.

The publication is the result of the Mongolian Vertebrate Parasite Project, made possible by NSF grants DEB-0717214, DBI-0646356, DBI-9631295, and DBI-9411976.

Rerooting The Evolutionary Tree Of Malaria Parasites, Diana C. Outlaw, Robert E. Ricklefs

Harold W. Manter Laboratory of Parasitology: Library Materials

Malaria parasites (Plasmodium spp.) have plagued humans for millennia. Less well known are related parasites (Haemosporida), with diverse life cycles and dipteran vectors that infect other vertebrates. Understanding the evolution of parasite life histories, including switches between hosts and vectors, depends on knowledge of evolutionary relationships among parasite lineages. In particular, inferences concerning time of origin and trait evolution require correct placement of the root of the evolutionary tree. Phylogenetic reconstructions of the diversification of malaria parasites from DNA sequences have suffered from uncertainty concerning outgroup taxa, limited taxon sampling, and selection on genes used to assess relationships. As …

Avian Influenza In Migratory Birds In The United States, 2007–2009, And Effects Of September Hunting Seasons On Survival, Harvest, And Recovery Rates Of Canada Geese Banded In Southeast Nebraska, Scott R. Groepper

School of Natural Resources: Dissertations, Theses, and Student Research

Highly-pathogenic avian influenza virus (HPAIV H5N1) poses risks to wild birds, poultry, and humans. Personnel with the United States Department of Agriculture-Animal Plant Health Inspection Service-Wildlife Services, state, and tribal wildlife agencies collected 168,940 samples from migratory birds from 2007 to 2009 to test for presence of HPAIV H5N1. No HPAIV was found, but other subtypes were discovered, including H5 and H7. I estimated prevalence of avian influenza virus by flyway and found prevalence was lowest each year in the Atlantic Flyway (6.7%–8.3%), highest in the Pacific Flyway in 2007 (13.3%) and 2008 (13.4%), and highest in the Mississippi Flyway …

Determining The Roles Of Dendritic Cells And Icam-1 In The Transpresentation Of Il-15 To Cd8 T Cells, Spencer W. Stonier

Dissertations and Theses (Open Access)

The maintenance and generation of memory CD8 T cells is dependent on the cytokine IL-15. IL-15 is delivered by a novel mechanism termed transpresentation: IL-15 is presented by a cell expressing IL-15Ralpha to the CD8 T cell which responds via IL-2Rbeta/gamma_c. The identity of what cells transpresent IL-15 to support the survival and homeostatic proliferation of memory CD8 T cells is unknown. Using a transgenic mouse model that limits IL-15 transpresentation to DCs, I have demonstrated that DCs transpresent IL-15 to CD8 T cells. DCs transpresent IL-15 to CD8 T cells during the contraction of an immune response …

Extracellular Atp Acts On P2y2 Purinergic Receptors To Facilitate Hiv-1 Infection, Claire Séror, Marie-Therese Melki, Frederic Subra, Syed Qasim Raza, Marlene Bras, Hela Saïdi, Roberta Nardacci, Laurent Voisin, Audrey Paoletti, Frederic Law, Isabelle Martins, Alessandra Amendola, Ali A. Abdul-Sater, Fabiola Ciccosanti, Olivier Delelis, Florence Niedergang, Sylvain Thierry, Najwane Said-Sadier, Christophe Lamaze, Didier Métivier, Jerome Estaquier, Gian Maria Fimia, Laura Falasca, Rita Casetti, Nazanine Modjtahedi, Jean M. Kanellopoulos, Jean-Francois Mouscadet, David M. Ojcius, Mauro Piacentini, Marie-Lise Gougeon, Guido Kroemer, Jean-Luc Perfetini

All Dugoni School of Dentistry Faculty Articles

Extracellular adenosine triphosphate (ATP) can activate purinergic receptors of the plasma membrane and modulate multiple cellular functions. We report that ATP is released from HIV-1 target cells through pannexin-1 channels upon interaction between the HIV-1 envelope protein and specific target cell receptors. Extracellular ATP then acts on purinergic receptors, including P2Y2, to activate proline-rich tyrosine kinase 2 (Pyk2) kinase and transient plasma membrane depolarization, which in turn stimulate fusion between Env-expressing membranes and membranes containing CD4 plus appropriate chemokine co-receptors. Inhibition of any of the constituents of this cascade (pannexin-1, ATP, P2Y2, and Pyk2) impairs the replication of HIV-1 mutant …

Determining The Roles Of Dendritic Cells And Icam-1 In The Transpresentation Of Il-15 To Cd8 T Cells, Spencer W. Stonier

Dissertations and Theses (Open Access)

The maintenance and generation of memory CD8 T cells is dependent on the cytokine IL-15. IL-15 is delivered by a novel mechanism termed transpresentation: IL-15 is presented by a cell expressing IL-15Ralpha to the CD8 T cell which responds via IL-2Rbeta/gamma_c. The identity of what cells transpresent IL-15 to support the survival and homeostatic proliferation of memory CD8 T cells is unknown. Using a transgenic mouse model that limits IL-15 transpresentation to DCs, I have demonstrated that DCs transpresent IL-15 to CD8 T cells. DCs transpresent IL-15 to CD8 T cells during the contraction of an immune response …

Enforced Expression Of Tbx1 In Fetal Thymic Epithelial Cells Antagonizes Thymus Organogenesis, Kim T. Cardenas

Dissertations and Theses (Open Access)

Enforced expression of Tbx1 in fetal thymic epithelial cells antagonizes

thymus organogenesis

Kim T. Cardenas

The thymus and parathyroid glands originate from organ-specific domains of 3rd pharyngeal pouch (PP) endoderm. At embryonic day 11.5 (E11.5), the ventral thymus and dorsal parathyroid domains can be identified by Foxn1 and Gcm2 expression respectively. Neural crest cells, (NCCs) play a role in regulating patterning of 3rd PP endoderm. In addition, pharyngeal endoderm influences fate determination via secretion of Sonic hedgehog (Shh), a morphogen required for Gcm2 expression and generation of the parathyroid domain. Gcm2 is a downstream target of the transcription factor Tbx1, …

Stat3 Controls The Neutrophil Migratory Response To Cxcr2 And Its Ligand Mip-2 (Cxcl2), Hoainam Nguyen-Jackson

Dissertations and Theses (Open Access)

Among the first white blood cells to respond to bacterial and fungal infections, neutrophils are produced in the bone marrow, released into circulating blood, and recruited to inflamed tissue. The cytokine granulocyte colony-stimulating factor (G��CSF) is used clinically to induce neutrophil mobilization from the marrow. This process was previously demonstrated to require the STAT3 transcription factor (signal transducer and activator of transcription 3), the principal signaling molecule activated upon G-CSF-binding of its receptor, but the mechanism was unknown. The chemokines KC (Cxcl1) and MIP-2 (Cxcl2), and their shared receptor CXCR2 (l8rb), also stimulate neutrophil mobilization, in contrast to SDF-1 (Cxcl12), …

Upregulation Of Reactive Oxygen Species During The Retrovirus Life Cycle And Their Roles In A Mutant Of Moloney Murine Leukemia Virus, Ts1-Mediated Neurodegeneration, Soo Jin Kim

Dissertations and Theses (Open Access)

Viral invasion of the central nervous system (CNS) and development of neurological symptoms is a characteristic of many retroviruses. The mechanism by which retrovirus infection causes neurological dysfunction has yet to be fully elucidated. Given the complexity of the retrovirus-mediated neuropathogenesis, studies using small animal models are extremely valuable. Our laboratory has used a mutant moloney murine leukemia retrovirus, ts1-mediated neurodegneration. We hypothesize that astrocytes play an important role in ts1-induced neurodegeneration since they are retroviral reservoirs and supporting cells for neurons. It has been shown that ts1 is able to infect astrocytes in vivo and in …

Novel Mechanisms Of Antigen Processing That Enhance Bcg Vaccine Efficacy, Christopher R. Singh

Dissertations and Theses (Open Access)

Mycobacterium tuberculosis, the causative agent of tuberculosis, is the most lethal single infectious agent afflicting man today causing 2 million deaths per year. The World Health Organization recommends a vaccine as the best option to prevent this disease. The current vaccine, BCG, has a variable efficacy and does not protect adults. It is known that BCG vaccine becomes sequestered in special phagosome compartments of macrophages that do not fuse with lysosomes. Since lysosome fusion is necessary for peptide production and T cell priming leading to protective T_H1 immunity, we hypothesized that vaccine efficacy is reduced and occurs perhaps …

Role Of Porcine Reproductive And Respiratory Syndrome Virus Non-Structural Protein 1 In Viral Replications And Pathogenesis, Lalit Kumar Beura

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

Porcine reproductive and respiratory syndrome virus (PRRSV) is an infectious agent of significant concern to the global swine industry. PRRSV infection of pigs is initiated by a long viremia after which the virus enters in an extended persistent phase of 3-4 months that ultimately is resolved by the immune system. The delayed and weak host adaptive response is responsible for the protracted convalescence period. An initial sub-optimal innate immune response is postulated to be the reason behind such meager adaptive immune response. A major focus of the studies undertaken in this dissertation was to identify the viral non-structural proteins (nsps) …

Glutaredoxin 2 Prevents H2o2-Induced Cell Apoptosis By Protecting Complex I Activity In The Mitochondria, Hongli Wu, Kuiyi Xing, Marjorie F. Lou

School of Veterinary and Biomedical Sciences: Faculty Publications

Glutaredoxin 2 (Grx2) belongs to the oxidoreductase family and is an isozyme of glutaredoxin 1 (Grx1) present in the mitochondria, however its function is not well understood. The purpose of this study is to evaluate the potential anti-apoptotic function of Grx2 by examining its ability to protect complex I in the mitochondrial electron transport system using human lens epithelial cells as a model. We found that cells treated with 200 μM hydrogen peroxide (H2O2) for 24 h exhibited decreased viability and became apoptotic with corresponding Bax up-regulation, Bcl-2 down-regulation, caspase 3 activation and mitochondrial cytochrome c leakage. Grx2 over-expression (OE) …

Regulation Of Cytosolic Phospholipase A2 (Cpla2) And Its Association With Cell Proliferation In Human Lens Epithelial Cells, Yin Wang, Kui-Yi Xing, Marjorie F. Lou

School of Veterinary and Biomedical Sciences: Faculty Publications

PURPOSE. To investigate the molecular mechanism for cytosolic phospholipase A2 (cPLA2) regulation and its association to platelet-derived growth factor (PDGF)-induced cell proliferation.

METHODS. cPLA2 was examined using human lens epithelial (HLE) B3 cells. Reactive oxygen species (ROS) generation induced by PDGF was analyzed by luminescence assay. Cell proliferation was measured by cell counting and by BrdU assay. Human cPLA2 gene was cloned via RT-PCR followed by sitedirected mutagenesis to construct HLE B3 cells expressing either inactive cPLA2 enzyme with S228A mutation (S228A), or cPLA2 truncated at the calcium-binding C2 domain (C2D). Activity of cPLA2 was measured by arachidonic acid (AA) …

Emerging Dynamics Of Human Campylobacteriosis In Southern Ireland, Susan Bullman, Daniel Corcoran, James O'Leary, Derry O'Hare, Brigid Lucey, Roy D. Sleator

Department of Biological Sciences Publications

Infections with Campylobacter spp. pose a significant health burden worldwide. The significance of Campylobacter jejuni/Campylobacter coli infection is well appreciated but the contribution of non-C. jejuni/C. coli spp. to human gastroenteritis is largely unknown. In this study, we employed a two-tiered molecular study on 7194 patient faecal samples received by the Microbiology Department in Cork University Hospital during 2009. The first step, using EntericBio® (Serosep), a multiplex PCR system, detected Campylobacter to the genus level. The second step, utilizing Campylobacter species-specific PCR identified to the species level. A total of 340 samples were confirmed as Campylobacter genus positive, 329 of …

Characterization Of The Serologic Responses To Plasmodium Vivax Dbpii Variants Among Inhabitants Of Pursat Province, Cambodia, Samantha Jones Barnes

USF Tampa Graduate Theses and Dissertations

The Plasmodium vivax Duffy Binding Protein (DBP) is the ligand in the major pathway for P. vivax invasion of human reticulocytes, making it an appealing vaccine candidate. Region II of DBP (DBP-RII) is the minimal portion of the ligand that mediates recognition of the Duffy Antigen Receptor for Chemokines (DARC receptor) on the reticulocyte surface and constitutes the primary vaccine target. Analysis of natural variation in the coding sequences of DBP-RII revealed signature evidence for selective pressure driving variation in the residues of the putative receptor-binding site. We hypothesize that anti-DBP immunity in P. vivax infections is strain-specific and hindered …

Mathematical Modeling And Dynamical Analysis Of The Operation Of The Hypothalamus - Pituitary - Thyroid (Hpt) Axis In Autoimmune (Hashimoto's) Thyroiditis, Balamurugan Pandiyan

Dissertations (1934 -)

This thesis is a mathematical modeling study of the operation of the negative feedback control through the hypothalamus-pituitary- thyroid (HPT) axis in autoimmune (Hashimoto's) thyroiditis. Negative feedback control through the HPT axis is a mechanism in which the high levels of thyroid hormone; free thyroxine (FT4) in the blood inhibits the secretion of the pituitary hormone, thyroid stimulating hormone (TSH) into the blood. Similarly, the low levels of free thyroxine (FT4) sensed by the pituitary gland and then it secretes thyroid stimulating hormone (TSH) into the blood. Autoimmune (Hashimoto's) thyroiditis is a disease in which the immune system turns against …

Caspase-1 Dependent Il-1Β Secretion Is Critical For Host Defense In A Mouse Model Of Chlamydia Pneumoniae Lung Infection, Kenichi Shimada, Timothy R. Crother, Justin Karlin, Shuang Chen, Norika Chiba, V. Krishnan Ramanujan, Laurent Vergnes, David M. Ojcius, Moshe Arditi

All Dugoni School of Dentistry Faculty Articles

Chlamydia pneumoniae (CP) is an important human pathogen that causes atypical pneumonia and is associated with various chronic inflammatory disorders. Caspase-1 is a key component of the ‘inflammasome’, and is required to cleave pro-IL-1β to bioactive IL-1β. Here we demonstrate for the first time a critical requirement for IL-1β in response to CP infection. Caspase-1^−/− mice exhibit delayed cytokine production, defective clearance of pulmonary bacteria and higher mortality in response to CP infection. Alveolar macrophages harbored increased bacterial numbers due to reduced iNOS levels in Caspase-1^−/− mice. Pharmacological blockade of the IL-1 receptor in CP infected wild-type mice …

Immune Evasion Of Porcine Reproductive And Respiratory Syndrome Virus Through Glycan Shielding Involves Both Glycoprotein 5 As Well As Glycoprotein 3, Hiep Vu, Byungjoon Kwon, Kyoung-Jin Yoon, William W. Laegreid, Asit K. Pattnaik, Fernando A. Osorio

School of Veterinary and Biomedical Sciences: Faculty Publications

Passive administration of porcine reproductive and respiratory syndrome virus (PRRSV) neutralizing antibodies (NAbs) can effectively protect pigs against PRRSV infection. However, after PRRSV infection, pigs typically develop a weak and deferred NAb response. One major reason for such a meager NAb response is the phenomenon of glycan shielding involving GP5, a major glycoprotein carrying one major neutralizing epitope. We describe here a type II PRRSV field isolate (PRRSV-01) that is highly susceptible to neutralization and induces an atypically rapid, robust NAb response in vivo. Sequence analysis shows that PRRSV-01 lacks two N-glycosylation sites, normally present in wild-type (wt) PRRSV strains, …