Immunology and Infectious Disease Commons^™

Transcriptomic Analysis Of Liver Indicates Novel Vaccine To Porcine Reproductive And Respiratory Virus Promotes Homeostasis In T-Cell And Inflammatory Immune Responses Compared To A Commercial Vaccine In Pigs, Damarius S. Fleming, Laura C. Miller, Jiuyi Li, Albert Van Geelen, Yongming Sang

Agricultural and Environmental Sciences Faculty Research

One of the largest impediments for commercial swine production is the presence of Porcine Reproductive and Respiratory Syndrome Virus (PRRSV), a devastating RNA viral infection that is responsible for over $1 billion in loss in the U.S. annually. The challenge with combating PRRSV is a combination of the effect of an extraordinary rate of mutation, the ability to infect macrophages, and subversion of host immune response through a series of actions leading to both immunomodulation and immune evasion. Currently there are a handful of commercial vaccines on the market that have been shown to be effective against homologous infections, but …

Immunometabolic Dysregulation At The Intersection Of Obesity And Covid-19, Collins N. Khwatenge, Marquette Pate, Laura C. Miller, Yongming Sang

Agricultural and Environmental Sciences Faculty Research

Obesity prevails worldwide to an increasing effect. For example, up to 42% of American adults are considered obese. Obese individuals are prone to a variety of complications of metabolic disorders including diabetes mellitus, hypertension, cardiovascular disease, and chronic kidney disease. Recent meta-analyses of clinical studies in patient cohorts in the ongoing coronavirus-disease 2019 (COVID-19) pandemic indicate that the presence of obesity and relevant disorders is linked to a more severe prognosis of COVID-19. Given the significance of obesity in COVID-19 progression, we provide a review of host metabolic and immune responses in the immunometabolic dysregulation exaggerated by obesity and the …

Cancer Salt Nostalgia, Aashish S. Allu, Venkataswarup Tiriveedhi

Biology Faculty Research

High-salt (sodium chloride) diets have been strongly associated with disease states and poor health outcomes. Traditionally, the impact of salt intake is primarily studied in cardiovascular diseases, hypertension and renal diseases; however, recently there has been increasing evidence demonstrating the role of salt in autoimmune diseases. Salt has been shown to modulate the inflammatory activation of immune cells leading to chronic inflammation-related ailments. To date, there is minimal evidence showing a direct correlation of salt with cancer incidence and/or cancer-related adverse clinical outcomes. In this review article, we will discuss the recent understanding of the molecular role of salt, and …

Epigenetic Evolution Of Ace2 And Il-6 Genes: Non-Canonical Interferon-Stimulated Genes Correlate To Covid-19 Susceptibility In Vertebrates, Eric R. Sang, Yun Tian, Laura C. Miller, Yongming Sang

Agricultural and Environmental Sciences Faculty Research

The current novel coronavirus disease (COVID-19) has spread globally within a matter of months. The virus establishes a success in balancing its deadliness and contagiousness, and causes substantial differences in susceptibility and disease progression in people of different ages, genders and pre-existing comorbidities. These host factors are subjected to epigenetic regulation; therefore, relevant analyses on some key genes underlying COVID-19 pathogenesis were performed to longitudinally decipher their epigenetic correlation to COVID-19 susceptibility. The genes of host angiotensin-converting enzyme 2 (ACE2, as the major virus receptor) and interleukin (IL)-6 (a key immuno-pathological factor triggering cytokine storm) were shown to evince active …

Influenza H3n2v: Key Facts For People Exhibiting Pigs At Fairs, Tennessee State University

Extension Publications

No abstract provided.

Dysregulated Interferon Response Underlying Severe Covid-19, Leann Lopez, Peter C. Sang, Yun Tian, Yongming Sang

Agricultural and Environmental Sciences Faculty Research

Innate immune interferons (IFNs), including type I and III IFNs, constitute critical antiviral mechanisms. Recent studies reveal that IFN dysregulation is key to determine COVID-19 pathogenesis. Effective IFN stimulation or prophylactic administration of IFNs at the early stage prior to severe COVID-19 may elicit an autonomous antiviral state, restrict the virus infection, and prevent COVID-19 progression. Inborn genetic flaws and autoreactive antibodies that block IFN response have been significantly associated with about 14% of patients with life-threatening COVID-19 pneumonia. In most severe COVID-19 patients without genetic errors in IFN-relevant gene loci, IFN dysregulation is progressively worsened and associated with the …

Immunogenetic Association Underlying Severe Covid-19, Kendall Mccoy, Autumn Peterson, Yun Tian, Yongming Sang

Agricultural and Environmental Sciences Faculty Research

SARS-CoV2 has caused the current pandemic of new coronavirus disease 2019 (COVID-19) worldwide. Clinical outcomes of COVID-19 illness range broadly from asymptotic and mild to a life-threatening situation. This casts uncertainties for defining host determinants underlying the disease severity. Recent genetic analyses based on extensive clinical sample cohorts using genome-wide association studies (GWAS) and high throughput sequencing curation revealed genetic errors and gene loci associated with about 20% of life-threatening COVID-19 cases. Significantly, most of these critical genetic loci are enriched in two immune signaling pathways, i.e., interferon-mediated antiviral signaling and chemokine-mediated/inflammatory signaling. In line with these genetic profiling studies, …

Impact Of Porcine Arterivirus, Influenza B, And Their Coinfection On Antiviral Response In The Porcine Lung, Damarius S. Fleming, Laura C. Miller, Yun Tian, Yonghai Li, Wenjun Ma, Yongming Sang

Agricultural and Environmental Sciences Faculty Research

Interferon (IFN) cytokines induce an autonomous antiviral state in cells of the infected site to restrict virus spreading and critically regulate overall antiviral response. The antiviral state leads to host protection through expression of hundreds of IFN-stimulated genes that restrict viral infection through multiple mechanisms, for example, directly in viral genome degradation and indirectly through cellular metabolic inhibition. Young pigs were split into four treatment groups: control, porcine reproductive and respiratory syndrome virus (PRRSV, also known as porcine arterivirus) infected, influenza B virus (IBV) infected, and IBV/PRRSV coinfection. Lung tissue was collected at 3, 5, and 7 days post infection …

Genomic Modeling As An Approach To Identify Surrogates For Use In Experimental Validation Of Sars-Cov-2 And Hunov Inactivation By Uv-C Treatment, Brahmaiah Pendyala, Ankit Patras, Bharat Pokharel, Doris D’Souza

Agricultural and Environmental Sciences Faculty Research

Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2) is responsible for the COVID-19 pandemic that continues to pose significant public health concerns. While research to deliver vaccines and antivirals are being pursued, various effective technologies to control its environmental spread are also being targeted. Ultraviolet light (UV-C) technologies are effective against a broad spectrum of microorganisms when used even on large surface areas. In this study, we developed a pyrimidine dinucleotide frequency based genomic model to predict the sensitivity of select enveloped and non-enveloped viruses to UV-C treatments in order to identify potential SARS-CoV-2 and human norovirus surrogates. The results revealed that …

Integrate Structural Analysis, Isoform Diversity, And Interferon-Inductive Propensity Of Ace2 To Predict Sars-Cov2 Susceptibility In Vertebrates, Eric R. Sang, Yun Tian, Yuanying Gong, Laura C. Miller, Yongming Sang

Agricultural and Environmental Sciences Faculty Research

The current new coronavirus disease (COVID-19) has caused globally over 0.4/6 million confirmed deaths/infected cases across more than 200 countries. As the etiological coronavirus (a.k.a. SARS-CoV2) may putatively have a bat origin, our understanding about its intermediate reservoir between bats and humans, especially its tropism in wild and domestic animals are mostly unknown. This constitutes major concerns in public health for the current pandemics and potential zoonosis. Previous reports using structural analysis of the viral spike protein (S) binding its cell receptor of angiotensin-converting enzyme 2 (ACE2), indicate a broad potential of SARS-CoV2 susceptibility in wild and particularly domestic animals. …

Prevalence Of Multidrug-Resistant Foodborne Pathogens And Indicator Bacteria From Edible Offal And Muscle Meats In Nashville, Tennessee, Siqin Liu, Agnes Kilonzo-Nthenge, Samuel N. Nahashon, Bharat Pokharel, Abdullah Ibn Mafiz, Maureen Nzomo

Agricultural and Environmental Sciences Faculty Research

This study investigated the prevalence of antimicrobial-resistant bacteria in retail edible offal and muscle meats in Nashville, Tennessee. A total of 348 retail meats (160 edible offal and 188 muscle) were analyzed for Salmonella enterica serovar, Campylobacter, Escherichia coli, E. coli O157:H7, and enterococci. Bacteria was identified using biochemical and PCR methods. Salmonella enterica serovar (4.4% and 4.3%), Campylobacter (1.9% and 1.1%), E. coli (79.4% and 89.4%), and enterococci (88.1% and 95.7%) was detected in offal and muscle meats, respectively. Chicken liver (9.7%) was most frequently contaminated with Salmonella enterica serovar, followed by ground chicken (6.9%) and chicken wings (4.2%). …

Probiotics And Antimicrobial Effect Of Lactiplantibacillus Plantarum, Saccharomyces Cerevisiae, And Bifidobacterium Longum Against Common Foodborne Pathogens In Poultry, Joy Igbafe, Agnes Kilonzo-Nthenge, Samuel N. Nahashon, Abdullah Ibn Mafiz, Maureen Nzomo

Agricultural and Environmental Sciences Faculty Research

The probiotic potential and antimicrobial activity of Lactiplantibacillus plantarum, Saccharomyces cerevisiae, and Bifidobacterium longum were investigated against Escherichia coli O157:H7, Salmonella typhimurium and Listeria monocytogenes. Selected strains were subjected to different acid levels (pH 2.5–6.0) and bile concentrations (1.0–3.0%). Strains were also evaluated for their antimicrobial activity by agar spot test. The potential probiotic strains tolerated pH 3.5 and above without statistically significant growth reduction. However, at pH 2.5, a significant (p < 0.05) growth reduction occurred after 1 h for L. plantarum (4.32 log CFU/mL) and B. longum (5.71 log CFU/mL). S. cerevisiae maintained steady cell counts for the entire treatment period without a statistically significant (p > 0.05) reduction (0.39 log CFU/mL). The results indicate at 3% bile concertation, 1.86 log CFU/mL reduction was observed for L. plantarum, while S. cerevisiae, and B. longum growth …

Perplexing Role Of P-Glycoprotein In Tumor Microenvironment, Kianna Robinson, Venkataswarup Tiriveedhi

Biology Faculty Research

Development of multidrug resistance (MDR) still remains a major obstacle to the long-term success of cancer therapy. P-glycoprotein (P-gp) is a well-identified membrane transporter with capability to efflux drug molecules out of the cancer cell leading to reduced efficiency of chemotherapy. Cancer cells upregulate P-gp expression as an adaptive response to evade chemotherapy mediated cell death. While several P-gp inhibitors have been discovered by in silico and pre-clinical studies, very few have successfully passed all phases of the clinical trials. Studies show that application of P-gp inhibitors in cancer therapy regimen following development of MDR achieved limited beneficial outcomes. While, …

Hiv-1 Did Not Contribute To The 2019-Ncov Genome, Chuan Xiao, Xiaojun Li, Shuying Liu, Yongming Sang, Shou-Jiang Gao, Feng Gao

Agricultural and Environmental Sciences Faculty Research

No abstract provided.

Viral Infections And Interferons In The Development Of Obesity, Yun Tian, Jordan Jennings, Yuanying Gong, Yongming Sang

Agricultural and Environmental Sciences Faculty Research

Obesity is now a prevalent disease worldwide and has a multi-factorial etiology. Several viruses or virus-like agents including members of adenoviridae, herpesviridae, slow virus (prion), and hepatitides, have been associated with obesity; meanwhile obese patients are shown to be more susceptible to viral infections such as during influenza and dengue epidemics. We examined the co-factorial role of viral infections, particularly of the persistent cases, in synergy with high-fat diet in induction of obesity. Antiviral interferons (IFNs), as key immune regulators against viral infections and in autoimmunity, emerge to be a pivotal player in the regulation of adipogenesis. In this review, …

Cross-Species Genome-Wide Analysis Reveals Molecular And Functional Diversity Of The Unconventional Interferon-Ω Subtype, Lauren E. Shields, Jordan Jennings, Qinfang Liu, Jinhwa Lee, Wenjun Ma, Frank Blecha, Laura C. Miller, Yongming Sang

Agricultural and Environmental Sciences Faculty Research

Innate immune interferons (IFNs), particularly type I IFNs, are primary mediators regulating animal antiviral, antitumor, and cell-proliferative activity. These antiviral cytokines have evolved remarkable molecular and functional diversity to confront ever-evolving viral threats and physiological regulation. We have annotated IFN gene families across 110 animal genomes, and showed that IFN genes, after originating in jawed fishes, had several significant evolutionary surges in vertebrate species of amphibians, bats and ungulates, particularly pigs and cattle. For example, pigs have the largest but still expanding type I IFN family consisting of nearly 60 IFN-coding genes that encode seven IFN subtypes including multigene subtypes …

Porcine Interferon Complex And Co-Evolution With Increasing Viral Pressure After Domestication, Jordan Jennings, Yongming Sang

Agricultural and Environmental Sciences Faculty Research

Consisting of nearly 60 functional genes, porcine interferon (IFN)-complex represents an evolutionary surge of IFN evolution in domestic ungulate species. To compare with humans and mice, each of these species contains about 20 IFN functional genes, which are better characterized using the conventional IFN-α/β subtypes as examples. Porcine IFN-complex thus represents an optimal model for studying IFN evolution that resulted from increasing viral pressure during domestication and industrialization. We hypothesize and justify that porcine IFN-complex may extend its functionality in antiviral and immunomodulatory activity due to its superior molecular diversity. Furthermore, these unconventional IFNs could even confer some functional and …

Immunogenicity Of Tumor Initiating Stem Cells: Potential Applications In Novel Anticancer Therapy, Durga Khandekar, Suneetha Amara, Venkataswarup Tiriveedhi

Biology Faculty Research

Tumor initiating stem cells (TISCs) are a subset of tumor cells, which are implicated in cancer relapse and resistance to chemotherapy. The metabolic programs that drive TISC functions are exquisitely unique and finely-tuned by various oncogene-driven transcription factors to facilitate pro-cancerous adaptive challenges. While this change in TISC metabolic machinery allows for the identification of associated molecular targets with diagnostic and prognostic value, these molecules also have a potential immunological application. Recent studies have shown that these TISC-associated molecules have strong antigenic properties enabling naïve CD8+T lymphocytes to differentiate into cytotoxic effector phenotype with anticancer potential. In spite of the …

Kinetic Analysis And Epitope Mapping Of Monoclonal Antibodies To Salmonella Typhimurium Flagellin Using A Surface Plasmon Resonance Biosensor, Devendra Bhandari, Fur-Chi Chen, Shreya Hamal, Roger C. Bridgman

Human Sciences Faculty Research

Salmonella Typhimurium is one of the leading causes of foodborne diseases worldwide. Biosensors and immunoassays utilizing monoclonal antibodies are widely used for the detection and subtyping of S. Typhimurium. However, due to insufficient information on the nature of binding with S. Typhimurium flagellin, the selection of appropriate antibodies for assay development is a cumbersome task. Hence, we aimed to compare the binding kinetics of a panel of monoclonal antibodies and their relative binding sites to flagellin antigen using a surface plasmon resonance biosensor. Initially, the flagellin was captured on the sensor surface through an immobilized anti-flagellin antibody. The interactions of …

Uv-C Treatment On The Safety Of Skim Milk: Effect On Microbial Inactivation And Cytotoxicity Evaluation, Danielle M. Ward, Ankit Patras, Agnes Kilonzo-Nthenge, Sudheer K. Yannam, Che Pan, Hang Xiao, Michael Sasges

Agricultural and Environmental Sciences Faculty Research

The efficacy of UV-C irradiation as a nonthermal processing method for skim milk (SM) was investigated. SM inoculated with two surrogate viruses (MS2 and T1UV), and three bacteria (Escherichia coli ATCC 25922, Salmonella enterica serovar Typhimurium ATCC 13311, and Listeria monocytogenes ATCC 19115) was treated with Deanflow UV-C irradiation, a spiral reactor with the fluid pumped around a central low-pressure mercury UV lamp (40 W) emitting at 254 nm wave-length. A series of known UV doses (0–168.33 mJ·cm²) were delivered to the samples. The microbial loads of MS2, T1UV, E. coli, Salmonella, and Listeria were …

Seroprevalence And Participatory Epidemiology Of Camelpox In Afar Region Of Ethiopia, Weldegebrial G. Aregawi, Getahun E. Agga, Jemal Gishe, Reta D. Abdi

Public Health, Health Administration, and Health Sciences Faculty Research

Camelpox is endemic in most camel rearing regions of the world, causing significant economic losses. However, its epidemiology is not extensively investigated. We conducted a cross sectional seroprevalence study of camelpox in Amibara and Awash Fentale districts in Afar region of Ethiopia from November 2014 to May 2015. In addition, participatory epidemiology (PE) was conducted to identify seasonal occurrence of the disease in the study districts. Blood samples were collected from 384 dromedary camels from 31 herds distributed in five pastoral associations (PAs) in the two districts. Serum samples were separated from the blood samples and tested for the presence …

Operationalizing Outcome Measures Of Human Papillomavirus Vaccination Among Adolescents, Chisom N. Odoh, Maureen Sanderson, Elizabeth A. Williams, Pamela C. Hull

Public Health, Health Administration, and Health Sciences Faculty Research

Objectives

When examining vaccination coverage, researchers must make decisions about how to define outcome measures based on many factors, including the timing of doses. Different operationalizations of the same outcome can often lead to different findings and can affect the ability to make comparisons across studies. This methodological article aimed to illustrate the implications of two options for operationalizing human papillomavirus (HPV) vaccination based on timing: initiation of the first dose at any age vs before the 13th birthday (on time).

Study design

Cross-sectional observational design.

Methods

The 2014 National Immunization Survey for Teens (N = 16,439 adolescents aged …

The Five Immune Forces Impacting Dna-Based Cancer Immunotherapeutic Strategy, Suneetha Amara, Venkataswarup Tiriveedhi

Biology Faculty Research

DNA-based vaccine strategy is increasingly realized as a viable cancer treatment approach. Strategies to enhance immunogenicity utilizing tumor associated antigens have been investigated in several pre-clinical and clinical studies. The promising outcomes of these studies have suggested that DNA-based vaccines induce potent T-cell effector responses and at the same time cause only minimal side-effects to cancer patients. However, the immune evasive tumor microenvironment is still an important hindrance to a long-term vaccine success. Several options are currently under various stages of study to overcome immune inhibitory effect in tumor microenvironment. Some of these approaches include, but are not limited to, …

Synergistic Effect Of Pro-Inflammatory Tnfα And Il-17 In Periostin Mediated Collagen Deposition: Potential Role In Liver Fibrosis, Suneetha Amara, Karina Lopez, Babak Banan, Sade-Kemi Brown, Margaret Whalen, Elbert L. Myles, Michael T. Ivy, Terrance Johnson, Kevin L. Schey, Venkataswarup Tiriveedhi

Biology Faculty Research

Background

The pro-inflammatory cytokines, tumor necrosis factor (TNF)-α, and interleukin (IL)-17, have been implicated in the pathogenesis of liver fibrosis. In this study, we investigated the role of TNFα and IL-17 toward induction of profibrotic factor, periostin.

Methods

HepG2 cells were cultured and treated with inflammatory cytokines, TNFα and IL-17. Computational promoter sequence analysis of the periostin promoter was performed to define the putative binding sites for transcription factors. Transcription factors were analyzed by Western blot and Chromatin Immunoprecipitation. Periostin and transcription factor expression analysis was performed by RT-PCR, Western blot, and fluorescence microscopy. Type I collagen expression from fibroblast …