Immunology and Infectious Disease Commons^™

Type 2 Bovine Viral Diarrhea Virus NPro Suppresses Type I Interferon Pathway Signaling In Bovine Cells And Augments Bovine Respiratory Syncytial Virus Replication, Abdulrahman Abdulaziz A. Alkheraif

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

Bovine viral diarrhea virus (BVDV) and bovine respiratory syncytial virus (BRSV) infections contribute to the bovine respiratory disease complex (BRDC), which is a multi-factorial disorder involving co-infections of viruses and bacteria including mycoplasma. BRDC causes great economic losses to the United States feedlot industry. BVDV infection induces immunosuppression in infected animals. BVDV N^pro binds and degrades the transcription factor interferon regulatory factor-3 (IRF-3) and effectively blocks type I interferon (type I IFN) expression in host cells. BRSV nonstructural proteins, NS1 and NS2, block activation of IRF-3. In calves, concurrent infection with BVDV and BRSV resulted in more severe clinical …

Role Of Neutrophils In The Modulation Of Host Responses To Human Respiratory Pneumovirus Infection, Nagarjuna Reddy Cheemarla

LSU Doctoral Dissertations

Neutrophils are the most abundant leukocytes (50% to 70%) in humans and are the first immune cell population recruited to the sites of infection. They are known to act as the first line of innate immune defense against invading pathogens, and more recently, to playing a crucial role in orchestrating adaptive immune responses. The role of neutrophils in the respiratory viral infections till date remains unclear and controversial. Previous studies demonstrated both beneficial as well as pathogenic role for neutrophils in respiratory viral infections, especially influenza.

Previous findings reported an early and high influx of neutrophils into the airways early …

Schistosomiasis In The Wild: A Transcriptomics Perspective On Field-Derived Biomphalaria Pfeifferi And Schistosoma Mansoni, And Their Interactions, Sarah K. Buddenborg

Biology ETDs

Schistosomiasis, caused by trematodes in the genus Schistosoma, is a widespread neglected tropical disease with the species S. mansoni infecting over 100 million people. We aimed to better understand the snail host and parasite responses during intramolluscan stages of infection by performing dual RNA-Seq on field-collected snails with natural infections from western Kenya. We collected uninfected Biomphalaria pfeifferi, B. pfeifferi with a patent cercariae-producing S. mansoni infection, and B. pfeifferi exposed to field-collected S. mansoni at 1 and 3d (days post infection).

We first created a high-quality B. pfeifferi transcriptome to identify the snail response to S. mansoni infection. …

Evolution Of Bordetella Pertussis Genome May Play A Role In The Increased Rate Of Whooping Cough Cases In The United States, Kevin Loftus

Senior Honors Projects, 2010-2019

Bordetella pertussis is the bacterium responsible for pertussis, a disease commonly referred to as whooping cough. Recently, pertussis has made a resurgence in the U.S. despite high-vaccination coverage. Possible causes of the increased number of pertussis cases include genetic evolution of B. pertussis, increased awareness of the disease, better laboratory diagnostics, and the switch from a whole-cellular (wP) vaccine to an acellular vaccine (aP) in the 1990s. Fortunately, just as B. pertussis is evolving, so is the arsenal of technologies used to understand and combat this pathogenic bacterium. Whole genome sequencing is one technology that helps researchers better understand …

Enhanced Production Of Pro-Il-1Βeta Contributes To Immunopathology During The Coinfection Of Influenza A Virus And Streptococcus Pneumoniae, Angeline E. Rodriguez

Graduate Theses/Dissertations

Viral bacterial coinfections are known to cause severe pneumonia, especially in the elderly and in pediatric patients. Antibiotics like β-Lactams kill the bacteria but fail to improve symptoms suggesting a faulty immune system may play an important role in the disease. Interleukin-1β (IL-1β) is an important immune signaling cytokine responsible for inflammation. It exists as an inactive precursor that can be activated by caspase-1 containing inflammasomes (multi-protein complex). Influenza A virus (IAV) and Streptococcus pneumoniae (S. pneumoniae) activate the inflammasome through the NOD-like receptor protein NLRP3 and/or AIM2. Previous reports in mice indicate that IL-1β levels are dramatically …

Investigation Into The Causes And Severity Of The 1918 Influenza Pandemic, Alex T. Freedenberg

The Review: A Journal of Undergraduate Student Research

The 1918 Influenza outbreak is regarded as one of the worst pandemics in human history due to its widespread effects across the globe and its high death rate. This death rate was unusual among influenza infections as most strains do not cause the amount of death that is seen in this outbreak, with 20 million dead as a conservative estimate and 100 million by other estimations. This pandemic was not very well contained for a plethora of reasons. Two main reasons are that it came at a time when understanding viral mechanics still escaped medical professionals, and due to the …

Genotype-Specific Insertion Of Cytotoxic Genetic Elements Into Cancer Cells, Ryan Englander

University Scholar Projects

The new gene editing system CRISPR/Cas9, composed of a complex composed of a guide RNA and the Cas9 endonuclease, promises to revolutionize biological research and potentially allow clinicians to directly modify patient DNA in vivo. While its applications in the treatment of genetic diseases and in modifying immune cells for immunotherapy are currently being explored, CRISPR/Cas9’s potential utility as a modular system for targeting tumor-specific mutated sequences has not as of yet been explored. While CRISPR/Cas9 is specific enough to target small insertions and deletions or gross chromosomal rearrangements, it is not specific enough to reliably restrict editing to …

Characterization Of The Interaction Between R. Conorii And Human Host Vitronectin In Rickettsial Pathogenesis, Abigail Inez Fish

LSU Doctoral Dissertations

Spotted Fever Group Rickettsia are inoculated into the mammalian host during hematophagous arthropod feeding. Once in the bloodstream and during dissemination, the survival of these pathogens is dependent upon their ability to evade innate host defenses until a proper cellular target is reached. The establishment of a successful infection also relies on the ability of the bacteria to attach and invade target cells, as failure to do so results in destruction of the bacterium. Rickettsia conorii expresses an outer membrane protein, Adr1, which binds the multifunctional human glycoprotein, vitronectin, to promote resistance to complement mediated killing. Homologs of Adr1 are …

Role Of Mucin 19 In The Respiratory Tract, Kaitlin Mcbride

LSU Master's Theses

Human metapneumovirus (HMPV) is a negative sense, single stranded RNA virus belonging to the Pneumoviridae family, and represents an important pathogen that causes severe respiratory disease worldwide. There is currently no vaccine against HMPV, so it is important to study the aspects of the immune response induced by HMPV. Because infiltration of mucus is a hallmark of HMPV infection, it is warranted to study the role of mucus in the disease process. Mucin proteins make up the major component of mucus and can be found within the airway and lungs. Previous work from our laboratory demonstrated a high upregulation of …

Developing Novel Therapeutics For Bacterial Lung Infections, Brandon J. Baer, Ruud Veldhuizen, Cory Yamashita

Western Research Forum

Background: Bacterial lung infections are leading causes of death worldwide. Unfortunately, increasing resistance to antibiotics and the inflammation often accompanying these infections are leading to poor outcomes despite antibiotic intervention. Complicating treatment further, the tree-like branching structure of the lung makes drug delivery to distal sites of infection difficult. Our research aims to address these challenges by developing new therapeutics and new tools to improve and assess drug delivery, bacterial killing and inflammation. Our therapy combines host defense peptides, which have been shown to kill antibiotic-resistant bacteria and down regulate inflammation, with a pulmonary vehicle, exogenous surfactant, that can improve …

Frequency And Factors Associated With Adult Immunization In Patients Visiting Family Medicine Clinics At A Tertiary Care Hospital, Karachi, Samar Zaki, Asma Usman, Swaleha Tariq, Sameena Shah, Iqbal Azam Syed, Waris Qidwai, Kashmira Nanji

Department of Family Medicine

Objective: The goal of this study was to determine the frequency and factors associated with adult immunization in patients visiting family medicine clinics at a tertiary care hospital in Karachi.
Methods: A cross-sectional study was conducted from March 2014 to March 2015 in a tertiary care hospital in Karachi, Pakistan. Participants more than 18 years were invited to participate in the study. A pretested questionnaire was used to collect information. Data were entered and analyzed using IBM SPSS Statistics for Windows, version 19.0 (Armonk, NY: IBM Corp).
Results: A total of 340 patients were surveyed. The majority of patients …

Factors Associated With Candida Albicans Dissemination Via The Intestinal Mucosa, Emily Rochac Argueta

Legacy Theses & Dissertations (2009 - 2024)

A murine model that established GI colonization of Candida albicans and eventual dissemination was identified to be lacking by Koh and others. Koh’s model specifically employed a tailored combination of neutropenia, intestinal damage, and microbiome dysbiosis that would allow C. albicans to gain an opportunistic advantage. His model provided new opportunities to study the details of C. albicans pathogenesis with a focus on the innate immune mechanisms responsible for controlling C. albicans within the intestinal mucosa. The long-term goal of this research project was to specifically study the factors associated with Candida albicans dissemination via the intestinal mucosa. The model …

Antibody Dependent Enhancement Of Visceral Leishmaniasis, Alan K. Mcnolty

All Master's Theses

Leishmaniasis is a parasitic disease caused by protozoans of the genus Leishmania. This vector-born disease, transmitted by biting phlebotomine sandflies, typically manifests in one of three ways. The cutaneous form of the disease is characterized by localized lesions of the skin and is by far the most common manifestation. The visceral form of the disease is caused by parasitic infiltration of internal organs, particularly the spleen, liver, and bone marrow. The mucocutaneous form is caused by parasitic infection of the mucosa in the nose or mouth. While cutaneous leishmaniasis (CL) is often self-healing, visceral leishmaniasis (VL) is fatal if …

Relationships Between Factors Influencing Biofilm Formation And Pathogen Retention In Complex Rhizosphere Microbial Communities, Aaron Coristine

Theses and Dissertations (Comprehensive)

Riparian wetlands are unique habitats facilitating all forms of life. The riverbanks of these environments provide ideal conditions for bacteria, plants, and higher organisms. Of particular interest to this research was the variation in microbial community structure at high, intermediate and poor water quality impacted areas. Assessing the capabilities of plants to retain microbial pathogens was identified. Root systems and corresponding soil are ideal locations for bacterial deposition, resulting in attachment at these areas. Biofilm production in these regions is important for long-term establishment, leading to persistence and potential naturalization. Opportunistic pathogens originating from mammalian fecal matter are introduced into …

Type Ix Secretion System: Characterization Of An Effector Protein And An Insight Into The Role Of C-Terminal Domain Dimeration In Outer Membrane Translocation., Lahari Koneru

Electronic Theses and Dissertations

Porphyromonas gingivalis and Tannerella forsythia are two of the primary pathogens that are associated in the etiology and progression of chronic periodontitis. In T. forsythia, KLIKK proteases are the recently identified group of proteolytic enzymes that are secreted through Type IX secretion system (T9SS). Among, these KLIKK proteases a synergistic relationship was observed between karilysin and mirolysin in invading the host complement system for the survival of the bacteria. Since, karilysin has been already characterized, in this study we propose to study about mirolysin through structural, biochemical and biological characterization. The obtained results from the experiments has shown the …

The Kinetics Of Type I Interferons During Influenza A Virus Infection, Margaret A. Myers

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Markov Models Reveal Host Controls Of Within-Host Disease Dynamics, Tara Stewart, Zoi Rapti, Carla E. Cáceres

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Gender Differences In Virologic Response After Antiretroviral Therapy In Treatment-Naïve Hiv-Infected Individuals: Results From The 550 Clinic Hiv Cohort Study., Andrea Reyes-Vega, Alejandra Loban, Kavitha Srinivasan, Stephen P. Furmanek, Conner English, Mary Bishop, Cathy Spencer, Daniel Truelove, Julio A. Ramirez, Anupama Raghuram, Paula Peyrani

Faculty and Staff Scholarship

Background

Controversy still exists regarding gender differences in virologic response between treatment-na•ve HIV-infected individuals. The objective of this study was to evaluate gender difference in virologic and immunologic response to antiretroviral therapy in treatment-na•ve HIV-infected individuals. Methods

This was a retrospective, observational study of treatment-na•ve HIV-infected individuals managed at the 550 clinic who started antiretroviral therapy (ART) between January 1st, 2010 and December 31, 2015. Patients with available viral load and CD4 counts before and one year after initiating ART were included in this study. Virologic suppression was defined as < 48 HIV-1 RNA copies/mL, and mmunologic recovery was defined as a CD4 count increase of at least 150 cells/mm3. Dichotomous variables were reported in number and percentages and analyzed using Chi-squared tests and Fisher’s exact (whichever was appropriate). Continuous variables were reported as median and interquartile range (IQR) and analyzed using Wilcox rank-sum tests. Multivariate analyses performed were logistic regressions with adjustment for other covariates. P value <0.05 was considered statistically significant. R version 3.3.2 was used for the statistical analysis. Results

A total of 70 women and 90 men were included …

Extended-Spectrum Antiprotozoal Bumped Kinase Inhibitors: A Review, Wesley C. Van Voorhis, J. Stone Doggett, Marilyn Parsons, Matthew A. Hulverson, Ryan Choi, Samuel L. M. Arnold, Michael W. Riggs, Andrew Hemphill, Daniel K. Howe, Robert H. Mealey, Audrey O. T. Lau, Ethan A. Merritt, Dustin J. Maly, Erkang Fan, Kayode K. Ojo

Veterinary Science Faculty Publications

Many life-cycle processes in parasites are regulated by protein phosphorylation. Hence, disruption of essential protein kinase function has been explored for therapy of parasitic diseases. However, the difficulty of inhibiting parasite protein kinases to the exclusion of host orthologues poses a practical challenge. A possible path around this difficulty is the use of bumped kinase inhibitors for targeting calcium dependent protein kinases that contain atypically small gatekeeper residues and are crucial for pathogenic apicomplexan parasites’ survival and proliferation. In this review, we review efficacy against the kinase target, the parasite growth in vitro, and in animal infection models, as well …

Trypanosome Lytic Factor Mediated Immunity Against Leishmania Sp., Jyoti Pant

Dissertations, Theses, and Capstone Projects

Trypanosome Lytic Factor (TLF) is an innate immunity complex that was originally discovered to protect against African Trypanosomes. The major components of TLF are Apolipoprotein A1 (APOA1), Apolipoprotein L1 (APOL1) and HPR (Haptoglobin Related Protein), where APOL1 is necessary and sufficient for trypanolysis. Recently we have shown that TLF ameliorates infections by cutaneous Leishmania species. Here we investigated the effect of different primate and human TLF against different Leishmania sp. Our result shows that TLF kills metacyclic promastigotes of cutaneous Leishmania sp. within immune cells such as neutrophils and macrophages by two different mechanism. Using transiently transfected and germline transgenic …

Characterization Of Filifactor Alocis And Its Immune Evasion Strategies Employed Against Human Neutrophils., Cortney Linn Armstrong

Electronic Theses and Dissertations

Periodontal disease is among the most common of inflammatory conditions and is caused by bacterial and host derived factors. The presence of bacteria drives the recruitment of neutrophils, professional phagocytes, to migrate to specific oral sites where they produce potent antimicrobials to kill their target. However, this inflammation and production of antimicrobials must be strictly regulated to minimize collateral host tissue damage. Human neutrophils recognized the oral pathogen Filifactor alocis through Toll-like receptor (TLR) 2 and upon binding, activated both p38 MAPK and ERK signaling pathways, known to be involved in neutrophil cell migration and degranulation. F. alocis also stimulated …

Osteopontin Facilitates West Nile Virus Neuroinvasion Via Neutrophil “Trojan Horse” Transport, Amber M. Paul, Dhiraj Acharya, Laurel Duty, E. Ashley Thompson, Linda Le, Dobrivoje S. Stokic, A. Arturo Leis, Fengwei Bai

Publications

West Nile virus (WNV) can cause severe human neurological diseases including encephalitis and meningitis. The mechanisms by which WNV enters the central nervous system (CNS) and host factors that are involved in WNV neuroinvasion are not completely understood. The proinflammatory chemokine osteopontin (OPN) is induced in multiple neuroinflammatory diseases and is responsible for leukocyte recruitment to sites of its expression. In this study, we found that WNV infection induced OPN expression in both human and mouse cells. Interestingly, WNV-infected OPN deficient (Opn−/−) mice exhibited a higher survival rate (70%) than wild type (WT) control mice (30%), suggesting OPN plays a …

Modeling Hiv Dynamics Following 3bnc117 Antibody Infusion, Samantha Erwin

Biology and Medicine Through Mathematics Conference

No abstract provided.

Mathematical Modeling For The Transmission Dynamics Of {\It Mycobacterium Marinum} Incorporating Intra-Host Variability, Lihong Zhao

Biology and Medicine Through Mathematics Conference

No abstract provided.

Lymphoid Hematopoiesis And The Role Of B-Cells In Transgenic Mouse Model Of Sickle Cell Disease, Christina Cotte

University Scholar Projects

Sickle cell disease (SCD) has been shown to be associated with decreased baseline immunity and thus increased susceptibility to infection. I sought to discern possible causes of this by looking into the correlations between SCD and hematopoiesis, the immune system and the neuroendocrine system, and ultimately by conducting experiments surrounding the impaired immune system of SCD. These experiments focused on the potential causes and effects of the diminution of B-1a cells in the SCD spleen. Adoptive transfers, infections with Streptococcus pneumoniae, and histologic imaging were conducted to establish if the diminution of the B-1a cells in the SCD spleen …

A Novel Role For Osteopontin In Facilitating West Nile Virus Neuroinvasion, Amber M. Paul

Dissertations

West Nile virus (WNV) is a positive-sensed, single-stranded RNA flavivirus that can cause human neuroinvasive diseases, including encephalitis, meningitis, and flaccid paralysis. The mechanisms by which WNV enters the central nervous system and the host-factors that are involved in WNV-neuroinvasiveness are not completely understood. Osteopontin (OPN), a multifunctional glycoprotein, has been implicated as a bio-marker for a number of neuroinflammatory diseases. In particular, secreted (s)OPN has been implicated to participate in recruitment of polymorphonuclear neutrophils (PMN) to sites of its expression, while PMNs have been suggested to act as WNV reservoirs. Therefore, sOPN recruitment of PMNs may contribute to neuroinvasive …

Elucidating The Role Of Interleukin-17a In West Nile Virus Infection, Dhiraj Acharya

Dissertations

West Nile virus (WNV) is a neurotropic flavivirus of significant public health importance for which no therapeutics and vaccine are currently available. Interleukin-17A (IL-17A) is an inflammatory cytokine that regulates diverse immune functions, while its role is unclear in host’s immune response to WNV. Furthermore, CD8⁺ T cells are crucial components of immunity and play a vital role in recovery from WNV infection. Here, we report a previously unrecognized function of IL-17A in regulating CD8⁺ T cell cytotoxicity. We show that WNV induces the expression of IL-17A in both mouse splenocytes and human peripheral blood mononuclear cells cultured …

Range-Wide Prevalence And Impacts Of Pseudocercosporella Inconspicua On Lilium Grayi And An Assessment Of L. Superbum And L. Michauxii As Reservoirs, Cindy L. Barrett

Electronic Theses and Dissertations

Lilium grayi (Gray’s Lily), a southern Appalachian endemic species, is threatened by a Lilium-specific fungal pathogen, Pseudocercosporella inconspicua. The disease is characterized by tan lesions that can cause early senescence, while also lowering seed production and viability. This project tested for P. inconspicua conidia and accessed health at nine locations. The disease was present and ubiquitous across the range of L. grayi. Through identification of P. inconspicua conidia in the field, L. superbum (Turk’s Cap Lily) was identified as an additional host, while L. michauxii (Michaux’s Lily) was disease-free. However, infection was inducible in both species. With …

A Comparative Analysis Of The West African Hemorrhagic Fevers Caused By The Lassa And Ebola Viruses, Emiene E. Amali-Adekwu

Selected Honors Theses

Lassa fever (LF) and Ebola Hemorrhagic Fever (EHF) are viral diseases endemic to West Africa.The etiological agent of Lassa fever is an enveloped virus from the Arenaviridae family and was first discovered in 1969 when two missionary nurses died of a mysterious illness in the town of Lassa in Borno state, Nigeria.1 This virus is animal-borne (zoonotic) and is carried by the animal vector Mastomys natalensis (multimammate rat). The Ebola virus is also zoonotic originating from fruit bats belonging to the Pteropodidae family.2 The first reported case of Ebola Virus Disease (EVD) was a principal who was believed to have …

Creation Of An Immunodeficient Hla-Transgenic Mouse (Humamice) And Functional Validation Of Human Immunity After Transfer Of Hla-Matched Human Cells, Yang Zeng, Bingrun Liu, Marie-Therese Rubio, Xinyue Wang, David M. Ojcius, Ruoping Tang, Antoine Durrbach, Zhitao Ru, Yusen Zhou, Yu-Chun Lone

All Dugoni School of Dentistry Faculty Articles

Research on human immunology has been hindered by the lack of optimal small animal models, given that the protective immune responses of human and non-human species show significant differences. However, due to ethical constraints[1] and the high cost of clinical trials, it is urgent to improve the current animal models that can mimic faithfully human physiology, particularly the human immune system (HIS). HIS mice had been generated recently by engrafting human hematopoietic stem cells (hHSCs) or human peripheral mononuclear cells (hPBMCs) into highly immuno-deficient mice such as NSG, NOG or NRG mice. However, a major experimental drawback for studies using …