Immunology and Infectious Disease Commons^™

Histone Deacetylase 8 Is A Novel Therapeutic Target For Mantle Cell Lymphoma And Preserves Natural Killer Cell Cytotoxic Function, January M. Watters

USF Tampa Graduate Theses and Dissertations

This study demonstrates for the first time that HDAC8 function is critical for MCL survival, and abrogating its activity in human primary NK cells does not interfere with NK IgG antibody directed ADCC therapies ex vivo. Human NK cells, isolated from healthy donors, are highly resistant to HDAC8 inhibitor treatment with PCI-34051. Even at the highest concentration, 20uM, no toxicity was observed. Conversely, MCL cell lines representative of the aggressive MCL subtype, classical MCL, were especially sensitive to PCI-34051, an HDAC8 selective inhibitor, treatment. Blocking HDAC8 activity and/or abrogating expression through shRNA silencing induced significant DNA damage, hyperacetylation of SMC3, …

Rna Virus-Mediated Changes In Organismal Oxygen Consumption Rate In Young And Old Drosophila Melanogaster Males, Eli Hagedorn, Dean Bunnell, Beate Henschel, Daniel Smith Jr, Stephanie Dickinson, Andrew Brown, Maria De Luca, Ashley Turner, Stanislava Chtarbanova

Research, Publications & Creative Work

Aging is accompanied by increased susceptibility to infections including with viral pathogens resulting in higher morbidity and mortality among the elderly. Significant changes in host metabolism can take place following virus infection. Efficient immune responses are energetically costly, and viruses divert host molecular resources to promote their own replication. Virus-induced metabolic reprogramming could impact infection outcomes, however, how this is affected by aging and impacts organismal survival remains poorly understood. RNA virus infection of Drosophila melanogaster with Flock House virus (FHV) is an effective model to study antiviral responses with age, where older flies die faster than younger flies due …

Atlas Of Ticks (Acari: Argasidae, Ixodidae) In Germany: 1st Data Update, Franz Rubel, Stefan Zaenker, Alexander Weigand, Dieter Weber, Lidia Chitimia-Dobler, Olaf Kahl

Harold W. Manter Laboratory of Parasitology: Library Materials

The first data update of the atlas of ticks in Germany published in 2021 is presented here. This atlas provides maps based on georeferenced tick locations of 21 species endemic in Germany as well as three tick species that are regularly imported to Germany. The data update includes the following numbers of newly georeferenced tick locations: 17 Argas reflexus, 79 Carios vespertilionis, 2 Dermacentor marginatus, 43 Dermacentor reticulatus, 4 Haemaphysalis concinna, 3 Haemaphysalis punctata, 3 Hyalomma rufipes, 3 Ixodes apronophorus, 9 Ixodes arboricola, 1 Ixodes ariadnae, 30 Ixodes canisuga, …

Relationship Between Treatment Comorbidities And Hiv Viral Suppression Among People Who Live With Aids In Johannesburg., Nwogo Immaculata Ekeji, Tolulope A. Osoba, Hebatullah Tawfik, Mehdi Agha

Journal of Social, Behavioral, and Health Sciences

HIV has globally infected over 37.9 million people, of which 28.2 million (73%) are on antiretroviral treatment, and 66% of those on treatment are virally suppressed. In South Africa, however, low rate of viral suppression (47%) among people living with HIV is a major health problem that has continued to fuel HIV prevalence. A cross-sectional quantitative research design was used to investigate the relationship between treatment comorbidities and viral suppression among HIV-infected adults aged 18–49 who were diabetic, had cancer, or tuberculosis in Johannesburg. HIV Care Continuum formed the theoretical framework for this research. An existing HIV-infected patient de-identifiable dataset …

Syndemics And Social Factors: Infectious Disease Patterns Within The Population Of People Experiencing Homelessness In The United States, Kathleen Berzonsky

Honors Program: Senior Projects (Public)

Individuals experiencing homelessness are at increased risk of suffering from infectious diseases. This is due to a number of social factors and healthcare disparities, as well as the idea of syndemics, by which diseases cluster together to worsen disease burden. Current intervention strategies approach treatment from a post-infection perspective, but reducing transmission rates of infectious diseases within the population of people experiencing homelessness will require a shift in the healthcare framework. The issue of people experiencing homelessness must be viewed through a biosocial lens, focusing on preventative care and treatment. I provide an overview of the social factors governing infectious …

Characterization Of Tick And Host-Associated Factors Linked To Induction Of Alpha-Gal Syndrome., Surendra Raj Sharma, Surendra Raj Sharma

Dissertations

Alpha-Gal Syndrome (AGS) is a delayed allergic reaction caused by specific IgE antibodies to the oligosaccharide galactose-α-1,3-galactose (α-gal) present in red meat. AGS is a growing concern globally, with over 34,000 confirmed cases in the United States alone. Studies have linked AGS to tick bites, which sensitizes hosts against α-gal antigens and elevates α-gal specific IgE. This dissertation investigates the role of tick and host-associated factors in AGS development. Microbiome analysis of Am. americanum ticks revealed a comprehensive core microbiome profile and showed that new Fransiella-like endosymbionts dominate and outcompete conventional tick Coxiella endosymbionts. Ticks subjected to tetracycline treatment showed …

In Silico Binding Of 2-Aminocyclobutanones To Sars-Cov-2 Nsp13 Helicase And Demonstration Of Antiviral Activity, Thahani S. Habeeb Mohammad, Yash Gupta, Cory T. Reidl, Vlad Nicolaescu, Haley Gula, Ravi Durvasula, Prakasha Kempaiah, Daniel P. Becker Ph.D.

Chemistry: Faculty Publications and Other Works

The landscape of viral strains and lineages of SARS-CoV-2 keeps changing and is currently dominated by Delta and Omicron variants. Members of the latest Omicron variants, including BA.1, are showing a high level of immune evasion, and Omicron has become a prominent variant circulating globally. In our search for versatile medicinal chemistry scaffolds, we prepared a library of substituted α-aminocyclobutanones from an α-aminocyclobutanone synthon (11). We performed an in silico screen of this actual chemical library as well as other virtual 2-aminocyclobutanone analogs against seven SARS-CoV-2 nonstructural proteins to identify potential drug leads against SARS-CoV-2, and more broadly against coronavirus …

Behavioural Defences Against Parasites Across Host Social Structures, Sebastian Stockmeier, Yuko Ulrich, Gregory F. Albery, Sylvia Cremer, Patricia C. Lopes

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

1. Animals exhibit a variety of behavioural defences against socially transmitted parasites. These defences evolved to increase host fitness by avoiding, resisting or tolerating infection.
2. Because they can occur in both infected individuals and their uninfected social partners, these defences often have important consequences for the social group.
3. Here, we discuss the evolution and ecology of anti-parasite behavioural defences across a taxonomically wide social spectrum, considering colonial groups, stable groups, transitional groups and solitary animals.
4. We discuss avoidance, resistance and tolerance behaviours across these social group structures, identifying how social complexity, group composition and interdependent social relationships may contribute to the …

Impact Of The Dimethyl Sulfoxide Reductase Superfamily On The Evolution Of Biogeochemical Cycles, Michael Wells, Minjae Kim, Denise M. Akob, Partha Basu, John F. Stolz

UK CARES Faculty Publications

The dimethyl sulfoxide reductase (or MopB) family is a diverse assemblage of enzymes found throughout Bacteria and Archaea. Many of these enzymes are believed to have been present in the last universal common ancestor (LUCA) of all cellular lineages. However, gaps in knowledge remain about how MopB enzymes evolved and how this diversification of functions impacted global biogeochemical cycles through geologic time. In this study, we perform maximum likelihood phylogenetic analyses on manually curated comparative genomic and metagenomic data sets containing over 47,000 distinct MopB homologs. We demonstrate that these enzymes constitute a catalytically and mechanistically diverse superfamily defined not …

A Draft Of The Genome Of The Gulf Coast Tick, Amblyomma Maculatum, Jose M.C. Ribeiro, Natalia J. Bayona-Vásquez, Khemraj Budachetri, Deepak Kumar, Julia Catherine Frederick, Faizan Tahir, Brant C. Faircloth, Travis C. Glenn, Shahid Karim

Faculty Publications

The Gulf Coast tick, Amblyomma maculatum, inhabits the Southeastern states of the USA bordering the Gulf of Mexico, Mexico, and other Central and South American countries. More recently, its U.S. range has extended West to Arizona and Northeast to New York state and Connecticut. It is a vector of Rickettsia parkeri and Hepatozoon americanum. This tick species has become a model to study tick/Rickettsia interactions. To increase our knowledge of the basic biology of A. maculatum we report here a draft genome of this tick and an extensive functional classification of its proteome. The DNA from a single …

Ferric Chloride-Induced Arterial Thrombosis And Sample Collection For 3d Electron Microscopy Analysis, Smita Joshi, Alexis N. Smith, Kanakanagavalli Shravani Prakhya, Hammodah Rawhi Hammodah Alfar, Joshua Lykins, Ming Zhang, Irina D. Pokrovskaya, Maria A. Aronova, Richard D. Leapman, Brian Storrie, Sidney W. Whiteheart

Saha Cardiovascular Research Center Faculty Publications

Cardiovascular diseases are a leading cause of mortality and morbidity worldwide. Aberrant thrombosis is a common feature of systemic conditions like diabetes and obesity, and chronic inflammatory diseases like atherosclerosis, cancer, and autoimmune diseases. Upon vascular injury, usually the coagulation system, platelets, and endothelium act in an orchestrated manner to prevent bleeding by forming a clot at the site of the injury. Abnormalities in this process lead to either excessive bleeding or uncontrolled thrombosis/insufficient antithrombotic activity, which translates into vessel occlusion and its sequelae. The FeCl3-induced carotid injury model is a valuable tool in probing how thrombosis initiates and progresses …

Eczema Monkeypoxicum In A Female Patient With Atopic Dermatitis, Emma Napoli, Madeline Frizzell, Clark Gravell, Sergio Vallejo, Shasta Theodore, Karen Chen, Huma Siddiqui, Justin Dunn, Dora Marrufo, Jose Cadena, Patrick J Danaher

Faculty, Staff and Student Publications

A female patient with atopic dermatitis who had recently received a tattoo presented with severe right ear pain and several vesiculopustular lesions. Over 1 week, she developed approximately 80 widely distributed lesions. Laboratory testing confirmed mpox (previously monkeypox) virus, and no further lesions developed after initiation of oral tecovirimat.

Association Of IsvSa3 With Multidrug Resistance In Salmonella Enterica Isolates From Cattle (Bos Taurus), Gentry L. Lewis, Robert J. Fenton, Etsuko Moriyama, John Dustin Loy, Rodney A. Moxley

School of Veterinary and Biomedical Sciences: Faculty Publications

Salmonella enterica is, globally, an important cause of human illness with beef being a significant attributable source. In the human patient, systemic Salmonella infection requires antibiotic therapy, and when strains are multidrug resistant (MDR), no effective treatment may be available. MDR in bacteria is often associated with the presence of mobile genetic elements (MGE) that mediate horizontal spread of antimicrobial resistance (AMR) genes. In this study, we sought to determine the potential relationship of MDR in bovine Salmonella isolates with MGE. The present study involved 111 bovine Salmonella isolates obtained collectively from specimens derived from healthy cattle or their environments …

Analysis Of Acquired Resistance Mechanisms To Osimertinib In Patients With Egfr-Mutated Advanced Non-Small Cell Lung Cancer From The Aura3 Trial, Juliann Chmielecki, Tony Mok, Yi-Long Wu, Ji-Youn Han, Myung-Ju Ahn, Suresh S Ramalingam, Thomas John, Isamu Okamoto, James Chih-Hsin Yang, Frances A Shepherd, Krishna C Bulusu, Gianluca Laus, Barbara Collins, J Carl Barrett, Ryan J Hartmaier, Vassiliki Papadimitrakopoulou

Faculty, Staff and Student Publications

Osimertinib, an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), potently and selectively inhibits EGFR-TKI-sensitizing and EGFR T790M resistance mutations. This analysis evaluates acquired resistance mechanisms to second-line osimertinib (n = 78) in patients with EGFR T790M advanced non-small cell lung cancer (NSCLC) from AURA3 (NCT02151981), a randomized phase 3 study comparing osimertinib with chemotherapy. Plasma samples collected at baseline and disease progression/treatment discontinuation are analyzed using next-generation sequencing. Half (50%) of patients have undetectable plasma EGFR T790M at disease progression and/or treatment discontinuation. Fifteen patients (19%) have >1 resistance-related genomic alteration; MET amplification (14/78, 18%) and EGFR C797X mutation …

The Immunomodulating Effects Of Delta-9 Tetrahydrocannabinol (Thc) And Cannabidiol (Cbd) In The Context Of Infection, Rose D. Goodman, Kate Rouse, Victor Jimenez

Annual Research Symposium

No abstract provided.

Sulforaphane Pre-Treatment Improves Cytoprotection Against Opportunistic Pathogens, Caleb Harrop, Nathan Clark

Annual Research Symposium

No abstract provided.

Comparison Of Two Diagnostic Assays For The Detection Of Serum Neutralizing Antibody To Porcine Epidemic Diarrhea Virus, Justin Brown, Korakrit Poonsuk, Ting-Yu Cheng, Chris Rademacher, Erin Kalkwarf, Liying Tian, Lauren A. Mckeen, Chong Wang, Luis Gimenez-Lirola, David Baum, Locke A. Karriker

School of Veterinary and Biomedical Sciences: Faculty Publications

Lactogenic immunity is important for the protection of piglets against many pathogens including porcine epidemic diarrhea virus. Circulating neutralizing antibodies levels in sow sera may help determine if a detectable immune response could confer protection to piglets. Neutralizing antibodies can be detected through various diagnostic assays. This study evaluated the diagnostic characteristics of two neutralizing antibody assays for porcine epidemic diarrhea virus neutralizing antibodies in serum of challenged gilts. Four treatment groups, control, non-vaccinated, vaccinated prior to challenge, and vaccinated following challenge, were comprised of 20 gilts. Serum sample were collected from each gilt prior to and following challenge with …

Cd5 Expression By Dendritic Cells Directs T Cell Immunity And Sustains Immunotherapy Responses, Mingyu He, Kate Roussak, Feiyang Ma, Nicholas Borcherding, Vince Garin, Mike White, Charles Schutt, Trine I Jensen, Yun Zhao, Courtney A Iberg, Kairav Shah, Himanshi Bhatia, Daniel Korenfeld, Sabrina Dinkel, Judah Gray, Alina Ulezko Antonova, Stephen Ferris, David Donermeyer, Cecilia Lindestam Arlehamn, Matthew M Gubin, Jingqin Luo, Laurent Gorvel, Matteo Pellegrini, Alessandro Sette, Thomas Tung, Rasmus Bak, Robert L Modlin, Ryan C Fields, Robert D Schreiber, Paul M Allen, Eynav Klechevsky

Faculty, Staff and Student Publications

The induction of proinflammatory T cells by dendritic cell (DC) subtypes is critical for antitumor responses and effective immune checkpoint blockade (ICB) therapy. Here, we show that human CD1c+CD5+ DCs are reduced in melanoma-affected lymph nodes, with CD5 expression on DCs correlating with patient survival. Activating CD5 on DCs enhanced T cell priming and improved survival after ICB therapy. CD5+ DC numbers increased during ICB therapy, and low interleukin-6 (IL-6) concentrations promoted their de novo differentiation. Mechanistically, CD5 expression by DCs was required to generate optimally protective CD5hi T helper and CD8+ T cells; further, deletion of CD5 from T …

Hucopia: An Atlas Of Human Vs. Sars-Cov-2 Interactome And The Comparative Analysis With Other Coronaviridae Family Viruses, Naveen Duhan, Rakesh Kaundal

Plants, Soils, and Climate Faculty Publications

SARS-CoV-2, a novel betacoronavirus strain, has caused a pandemic that has claimed the lives of nearly 6.7M people worldwide. Vaccines and medicines are being developed around the world to reduce the disease spread, fatality rates, and control the new variants. Understanding the protein-protein interaction mechanism of SARS-CoV-2 in humans, and their comparison with the previous SARS-CoV and MERS strains, is crucial for these efforts. These interactions might be used to assess vaccination effectiveness, diagnose exposure, and produce effective biotherapeutics. Here, we present the HuCoPIA database, which contains approximately 100,000 protein-protein interactions between humans and three strains (SARS-CoV-2, SARS-CoV, and MERS) …

Fgl2-Targeting T Cells Exhibit Antitumor Effects On Glioblastoma And Recruit Tumor-Specific Brain-Resident Memory T Cells, Qingnan Zhao, Jiemiao Hu, Lingyuan Kong, Shan Jiang, Xiangjun Tian, Jing Wang, Rintaro Hashizume, Zhiliang Jia, Natalie Wall Fowlkes, Jun Yan, Xueqing Xia, Sofia F Yi, Long Hoang Dao, David Masopust, Amy B Heimberger, Shulin Li

Faculty, Staff and Student Publications

Although tissue-resident memory T (TRM) cells specific for previously encountered pathogens have been characterized, the induction and recruitment of brain TRM cells following immune therapy has not been observed in the context of glioblastoma. Here, we show that T cells expressing fibrinogen-like 2 (FGL2)–specific single-chain variable fragments (T-αFGL2) can induce tumor-specific CD8+ TRM cells that prevent glioblastoma recurrence. These CD8+ TRM cells display a highly expanded T cell receptor repertoire distinct from that found in peripheral tissue. When adoptively transferred to the brains of either immunocompetent or T cell-deficient naïve mice, these CD8+ TRM cells reject glioma cells. Mechanistically, T-αFGL2 …