Immunology and Infectious Disease Commons^™

Breaking Into Hiv-1'S Epigenetic Vault: Cure Strategies To Eliminate The Viral Reservoir, Joanna Jones, Chelsea Gunderson, Brian Wigdahl, Michael Nonnemacher

Kimmel Cancer Center Faculty Papers

Human immunodeficiency virus type 1 (HIV-1) is a retrovirus that integrates into the host cell's DNA as a provirus. Transcription from the provirus is regulated in large part by cellular proteins and epigenetic factors. These may be repressive or permissive to productive infection. The host factors that regulate this balance are therefore attractive targets for HIV-1 therapeutics. Indeed, proviral chromatin is the focus of two of the current HIV-1 cure strategies. "Shock and Kill" uses latency reversal agents to open the provirus's chromatin, promoting high levels of gene expression that induce the killing of infected cells. "Block and Lock" uses …

A Survey-Based Exploratory Study Of Factors Influencing Women's Intentions To Utilise Pre-Exposure Prophylaxis In The Eastern Cape Province, South Africa: Sociodemographic Characteristics, Hiv Risk Behaviours And Transactional Sex, Rosemary Kalenga, Gary Sharp, Anne M. Teitelman, Monde Makiwane, Larry D. Icard, John B. Jemmott

College of Nursing Faculty Papers & Presentations

BACKGROUND: South Africa has the third-highest adult prevalence rate globally, with women comprising 64% of cases. Despite the accessibility of pre-exposure prophylaxis (PrEP), its adoption among women, particularly young women, remains alarmingly low.

OBJECTIVES: The objective of this initial investigation is to explore factors influencing the intentions of South African women to use PrEP, focusing on sociodemographic factors, HIV sexual risk behaviours and involvement in transactional sex.

DESIGN: The research utilised an exploratory design employing surveys.

METHODS: Surveys were conducted in 2015 with 64 women aged 19-49 residing in the Eastern Cape Province of South Africa. The data were analysed …

No Effect In Plasma Corticosterone Levels After Observation Of Diseased Conspecifics, B. M. Hardy, M. Chang, S. Mccallum, S. Santangelo, Patricia C. Lopes

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Organisms commonly respond to stressors in their environment by increasing the secretion of corticosterone (CORT). While increased CORT is acknowledged as a response to predation risk by organisms inhabiting a landscape of fear, new research raises the potential for changes in CORT as a response to the risk of infection by organisms in their environment. An increase in CORT of a healthy, uninfected individual in response to their perception of the risk of infection in their environment could change their susceptibility to infection, highlighting a significant role for CORT to alter host–pathogen dynamics. To investigate the effects of infection risk …

Evaluation Of Il-10 And Il-12 As Early Diagnostic Biomarkers In Type 2 Diabetes Mellitus, Mariam Sami Shail, Israa Hussein Hamzah

Maaen Journal for Medical Sciences

Background: Type 2 diabetes mellitus (T2DM) is increasingly recognized as a complex metabolic disorder associated with immune dysregulation and chronic low-grade inflammation Objectives: This study aimed to quantify serum levels of (IL-10) and (IL-12) in patients with (T2DM) and to explore their potential role as early diagnostic biomarkers in comparison with healthy controls. Methods:  A case–control study be situated showed including 120 participants: 80 patients with T2DM and 40 healthy controls. Serum concentrations of IL-10 and IL-12 were quantified using ELISA. Hematological and biochemical parameters were assessed using standard automated methods. Statistical analyses included independent t-tests, correlation analysis, and receiver …

Fisheries Occasional Publication No. 150 - Response To 2024 External Review Of Integrated Stock Assessments For Key Wa Demersal Indicator Stocks, Rubie Evans-Powell, S. A. Hesp, Ainslie Denham, Emily A. Fisher, Rachel Marks, Fabian I. Trinnie, Brett Crisafulli

Fisheries Occasional Publications

In Western Australia (WA), stock assessments for key demersal species, including snapper and red emperor, have traditionally used bespoke integrated models developed in-house by the Department of Primary Industries and Regional Development (DPIRD). In line with other Australian jurisdictions, DPIRD is transitioning to Stock Synthesis (SS) as its primary platform for integrated stock assessments of WA finfish. To support this transition, DPIRD commissioned an independent expert review of recent integrated models applied to three demersal stocks. This publication responds to recommendations from Professor André Punt (University of Washington and CSIRO) in his 2024 review, which examined assessments for Pilbara red …

Cytotoxic And Antimicrobial Effects Of Plant-Derived Compounds Used In Traditional Chinese Medicine, Amanda Ly, Diane Sun, Shelbi Salinas, Victor M. Jimenez

Annual Research Symposium

No abstract provided.

Mycobacteria Infection Induced Cascade Of Epigenetic Alterations Promote Training In Bystander Macrophages, Shah E. Jahan Gulzar Mr

Theses and Dissertations

Mycobacterium tuberculosis (Mtb) remodels host cell functions to support its intracellular persistence. While the effects of Mtb infection on infected macrophages are well characterized, responses of uninfected bystander cells in the same microenvironment remain poorly understood. Here, we show that Mtb infection triggers widespread epigenetic reprogramming not only in infected macrophages but also in neighbouring bystander cells. These bystander macrophages acquire active chromatin marks, exhibit distinct transcriptional changes, and display enhanced immune responsiveness, thereby increasing resistance to both homologous and heterologous infections. We identify interleukin-1 beta secreted by infected cells as a key mediator of this process. Functionally, trained bystander …

Gene Regulatory Programs Of Nk Cells Show That Ncam1 (Cd56) And Kirs Are Controlled By Genetically Polymorphic Distal Regulatory Elements, Mariam A. Salem, Aditi Varkey, Matthew D. Estrada, Kruthika Sharma, Caprice D. Eisele, Nitin Chakravarti, Dean A. Lee, Aharon G. Freud, Bethany L. Mundy-Bosse, Patrick L. Collins

Kimmel Cancer Center Faculty Papers

Owing to their immunoprotective properties, natural killer (NK) cells are critical for the innate immune response to pathogens, as well as a new wave of cancer immunotherapy that harnesses natural cytotoxicity. We sought to study the genetic and epigenetic drivers behind human-specific NK cell receptors, so that we can better understand the underlying cellular function. Here, we present a transcriptomic, proteomic (CITE-seq), and chromatin (single nuclei ATAC-seq) profiling of human peripheral NK cell subsets, which was then compared with genomic databases. Through integrative multi-omics, we demonstrate that CD56^bright versus CD56^dim NK cell subsets have differential distal regulatory element …

Immunogenicity And Efficacy Of A Rabies-Based Vaccine Against Highly Pathogenic Influenza H5n1 Virus, Nir Paran, Christoph Wirblich, Randy Albrecht, Leila Zabihi Diba, Alessandro Tarquinio, Drishya Kurup, Charalambos C. Solomides, Adolfo García-Sastre, Matthias J. Schnell

Department of Microbiology and Immunology Faculty Papers

The recent spillover of highly pathogenic influenza A/H5N1 (HPAI-H5N1) viruses to cattle, other mammals, and humans poses a major risk to animal and human health. Virus adaptation to new species highlights the need for effective vaccines for animals and humans. We recently developed a rabies virus-based H5 vaccine encoding the HPAI-H5 antigen and presenting it on the surface of the rabies virus particle. To test the immunogenicity and efficacy of the vaccine in eliciting systemic and mucosal immune response, we vaccinated mice intramuscularly or intranasally with either live or inactivated and adjuvanted vaccine. The vaccine elicited neutralizing antibodies against RABV …

Combined Glycoprotein Mutations In Rabies Virus Promote Astrocyte Tropism And Protective Cns Immunity In Mice, Mirjam Anna Rita Bertoune, Corinna Kolbe, Ann-Cathrin Werner, Maren Steinmetz, Bernhard Dietzschold, Eberhard Weihe

Department of Microbiology and Immunology Faculty Papers

Rabies virus (RABV) causes fatal encephalitis once it invades the central nervous system (CNS), and treatment options are extremely limited at this stage. We investigated the recombinant RABV variants SPBN, SPBNGA (glycoprotein substitution R333E), SPBNGAK (R333E plus N194K), SPBNGAS (R333E plus N194S), and TriGAS (three copies of the R333E/N194S glycoprotein). We evaluated their cellular tropism and immune activation in an intracerebral mouse infection model using immunohistochemistry and confocal immunofluorescence. SPBNGAK (R333E/N194K) resulted in mixed neuronal and astrocytic infection and lethal disease. In contrast, the R333E/N194S mutations in the GAS variants were associated with reduced neuronal infection and apparent astrocyte-restricted infection …

Phase 1b/2 Study Of Bms-813160, A Ccr2/5 Dual Antagonist, In Combination With Chemotherapy Or Nivolumab In Patients With Advanced Pancreatic Or Colorectal Cancer, Dung T. Le, Gunnar Folprecht, Anna M. Varghese, Martin Gutierrez, Marcus Noel, Nikolaos A. Trikalinos, Eric Chen, Farshid Dayyani, S. Lindsey Davis, Wen Wee Ma, Atrayee Basu Mallick, Ignacio Garrido-Laguna, Mayu Osawa, Shaun O'Brien, Ruslan D. Novosiadly, Ke Xu, Danielle M. Greenawalt, Santanu Dutta, Christina Twyman Saint Victor, Heinz-Josef Lenz

Department of Medical Oncology Faculty Papers

BACKGROUND: Cysteine-cysteine chemokine receptors 2 (CCR2) and 5 (CCR5) contribute to immune suppression in tumor microenvironments. CCR2 and CCR5 antagonists have demonstrated antitumor activity in pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer (CRC), respectively. This phase 1b/2, open-label study evaluated BMS-813160, a CCR2/5 dual antagonist, in combination with chemotherapy±nivolumab in advanced PDAC or metastatic CRC.

METHODS: Part 1 included patients with metastatic untreated (first-line (1L)) PDAC, 1L CRC, or previously treated (second or third line (2/3L)) microsatellite stable (MSS) CRC. Patients received 2 weeks of BMS-813160 monotherapy (300 mg two times a day, 600 mg once daily, 300 mg once …

Contribution To The Chemotherapy Of Human Trypanosomiasis: Design, Synthesis, And Biological Evaluation Of Dimeric 2-Nitroimidazoles Against Trypanosoma Cruzi Amastigotes And Bloodstream Trypanosoma Brucei, Afonso Santine M.M. Velez, Otavio Augusto Chaves, Carlos Serpa, Fatma M. Salem, Bibo Li Ph.D., Bin Su Ph.D., Celio Geraldo Freire-De-Lima, Debra Decote-Ricardo, Marco Edilson Freire De Lima

Biological, Geological, and Environmental Faculty Publications

Effective and safe treatments for neglected tropical diseases caused by parasites, such as Chagas disease and sleeping sickness, remain lacking, posing a significant challenge for researchers worldwide. The rational design of dimeric compounds inspired solely by the pharmacophoric core of benznidazole (2-nitroimidazole) has proven to be a promising strategy for antiparasitic development. Thus, in the present work, it was increased the linker between the active units (2-nitroimidazole) to improve the interaction with TcNTR, facilitating the bioactivation of the longest dimers. Biological assays confirmed this, demonstrating that all compounds were active against replicative intracellular amastigotes of Trypanosoma cruzi (Tulahuen C2C4-LacZ). Notably, …

A Probabilistic Modeling Analysis Of The Longitudinal Immune Response To Infection And Vaccination Across Demographic Groups And Pulmonary Symptoms, James O'Hanlon, Kaitlyn Sullivan, Lyndsey M. Muehling, Glenda Canderan, Jie Sun, Judith A. Woodfolk, Jeffrey M. Wilson, Rayanne A. Luke

Spora: A Journal of Biomathematics

Antibody and cytokine kinetics describe the dynamic response to immune events such as infection and vaccination. These dynamics are not fully understood, and mathematical characterization may help explain variability across demographic groups and pulmonary symptoms post-acute infection. We fit time-dependent probability models to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) data to obtain distributions of longitudinal antibody response and cytokine values. To assess differences between groups, an overlap metric is applied to the modeled response curves. Our antibody models suggest significant differences between male and female populations and demonstrate deficient antibody responses of less-healthy groups such as smokers. Our cytokine …

Decoding Early Covid-19 Responses Using Mathematical Modeling Of Social Distancing Strategies Across Multiple Countries, Sri Gunturu, Suki Lewis, Katelyn Nguyen, Asma Azizi

Spora: A Journal of Biomathematics

During the early phase of the COVID-19 pandemic, before vaccines were available, countries implemented diverse combinations of social-distancing (SD) measures shaped by cultural norms and public acceptance. These differences produced varied outcomes in controlling viral spread, offering lessons for future health-crisis preparedness. We performed a reverse-engineering analysis of early COVID-19 case data from five socioculturally distinct countries—India, Vietnam, Italy, Finland, and the United States—selected to capture a range of initial prevalence levels. Using mathematical modeling and data fitting, we inferred the relative contributions of three SD interventions: face masking, quarantine, and isolation of infected individuals. We then employed an efficiency …

Surveillance Of A Novel Vesivirus Discovered In An Urban Mephitis Mephitis Population, Amanda E. Diggins

Honors Theses and Capstones

Caliciviridae is a family of non-enveloped, positive-sense, single stranded RNA viruses, including eleven defined genera that contain important pathogens of humans and animals. Within the Caliciviridae family, the genus Vesiviridae includes feline calicivirus, a leading cause of upper respiratory disease in cats, and vesicular exanthema of swine virus, a historical disease of domestic swine that has now been implicated in several marine mammal vesicular diseases, one of which has been confirmed zoonotic. Urban landscapes create a unique environment for rapid intra- and interspecies transmission of viruses. Clustered resources attract high-density populations of synanthropic wildlife species, increasing spatial overlap and heightening …

The Rhesus Macaque Model Of Mycobacterium Avium Infection Reveals That Age-Related Disease Is Due In Part To Chronic Inflammation And Lung Microbial Dysbiosis, Ethan G. Napier

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Aging is associated with dysregulated immunity and increased susceptibility to infection, a phenomenon dubbed as immunosenescence and characterized by reduced naïve T and B cell pools, altered innate immune function, and chronic low-grade inflammation. Nontuberculous mycobacterial (NTM) pulmonary disease (NTMPD) is an increasingly relevant chronic lung infection that disproportionately affects older adults (65+ years) and immunocompromised individuals. However, the host factors underlying increased disease severity in aged patients remain poorly defined. Literature suggests that effective control of NTM relies on coordinated innate and adaptive immune responses, particularly macrophage activation and Th1 cytokine signaling. Using a rhesus macaque model that closely …

A Framework For Characterizing The Peripheral Immune Isonome Using Long-Read Single-Cell Rna Sequencing And Its Relevance To Neurological Disease, Patricia Hayes Doyle

Theses and Dissertations--Neuroscience

Long-read single-cell RNA sequencing provides an opportunity to understand human health and disease at isoform resolution, revealing cellular diversity and disease mechanisms difficult to resolve with bulk or short-read methodologies.

Using a modified PIPseq workflow and computational pipeline adapted for Oxford Nanopore (ONT) sequencing, we profiled isoform usage across immune cells, integrating marker expression and isoform discovery, generating the largest long-read single-cell dataset of human immune cells from a single individual to date. We identified non-canonical protein-coding variants of GZMB and CD3G enriched in unexpected cell types. We also discovered novel transcripts from CMC1 and LYAR with cell-type-specific signatures that …

Equid Major Histocompatibility Complex (Mhc) Evolution & Genome Organization, Lauren C. Johnson

Theses and Dissertations--Veterinary Science

The evolution of modern horses has a well-documented fossil record and has long been of interest to the genetics community. Although non-caballine equids (e.g. zebras, donkeys, and asses) can hybridize with horses, the resulting offspring are typically infertile. Despite these reproductive barriers, genomic analyses reveal regions of high sequence similarity among equid species. This dissertation investigates the role of historical introgression in the evolution of modern Equus species. The first chapter re-evaluates earlier findings derived from a limited horse population and a single reference genome. The variants of the identified regions were pushed through Ensembl’s Variant Effect Predictor to assess …

Nanoparticle Carriers Enhance The Prophylactic Antiviral Effects Of Dsrna In Vitro And Ex Vivo, Shayne Oberhoffner, Stephanie Dewitte-Orr, Starla Richardson, Leah Haile, Dominique Daniels, Erin Cooper, Aizah Ijaz, Janet Velasquez Perez, Mathilde Peruzzi, Bertrand Collet, Paul Craig, Kristof Jenik

Theses and Dissertations (Comprehensive)

Aquaculture now outpaces traditional capture fisheries as the world population and demand for sustainable protein sources increases. Wild and farmed species are increasingly susceptible to pathogen spread as global temperatures rise and stocking densities increase. Despite the devastating losses experienced by aquaculture due to viral infections, there remain few effective prophylactic antiviral therapeutics. Long double-stranded (ds)RNA is a uniquely viral molecule produced by nearly all viruses during their replication cycle, and its detection by salmonids like rainbow trout (Oncorhynchus mykiss) and chinook salmon (Oncorhynchus tshawytsha) leads to the establishment of a defensive antiviral state. Previous in vitro studies demonstrated a …

Comparative Spatial Biology: A Cross-Species Analysis Of Canine Oral Cancers As Models For Human Disease, Ram Pradhyumnan

Honors Undergraduate Theses

Oral squamous cell carcinoma (OSCC), one of the most common malignancies of the oral cavity, remains a clinically challenging disease due to its aggressive behavior, late-stage diagnosis, and limited improvements in therapeutic outcomes over recent decades. A significant barrier to progress in OSCC research and treatment is the lack of suitable preclinical models that recapitulate the complexity and natural progression of the disease. Most current models—including cell lines, xenografts, and genetically engineered mice—fail to capture key features such as the spatial organization of tumor epithelium, interactions with an intact immune system, and the stepwise evolution from normal mucosa to invasive …