Virology Commons^™

Influenza C And D Viruses Demonstrated A Differential Respiratory Tissue Tropism In A Comparative Pathogenesis Study In Guinea Pigs, Chithra C. Sreenivasan, Runxia Liu, Rongyuan Gao, Yicheng Guo, Ben M. Hause, Milton Thomas, Ahsan Naveed, Travis Clement, Dana Rausch, Jane Christopher-Hennings, Eric Nelson, Julian Druce, Miaoyun Zhao, Radhey S. Kaushik, Qingsheng Li, Zizhang Sheng, Dan Dan, Feng Li

Nebraska Center for Virology: Faculty Publications

Influenza C virus (ICV) is increasingly associated with community-acquired pneumonia (CAP) in children and its disease severity is worse than the influenza B virus, but similar to influenza A virus associated CAP. Despite the ubiquitous infection landscape of ICV in humans, little is known about its replication and pathobiology in animals. The goal of this study was to understand the replication kinetics, tissue tropism, and pathogenesis of human ICV (huICV) in comparison to the swine influenza D virus (swIDV) in guinea pigs. Intranasal inoculation of both viruses did not cause clinical signs, however, the infected animals shed virus in nasal …

Adenoviral-Vectored Epigraph Vaccine Elicits Robust, Durable, And Protective Immunity Against H3 Influenza A Virus In Swine, Erika M. Petro-Turnquist, Matthew J. Pekarek, Nicholas Jeanjaquet, Cedric Wooledge, David J. Steffen, Hiep Vu, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

Current methods of vaccination against swine Influenza A Virus (IAV-S) in pigs are infrequently updated, induce strain-specific responses, and have a limited duration of protection. Here, we characterize the onset and duration of adaptive immune responses after vaccination with an adenoviral-vectored Epigraph vaccine. In this longitudinal study we observed robust and durable antibody responses that remained above protective titers six months after vaccination. We further identified stable levels of antigen-specific T cell responses that remained detectable in the absence of antigen stimulation. Antibody isotyping revealed robust class switching from IgM to IgG induced by Epigraph vaccination, while the commercial comparator …

Exercise Reprograms The Inflammatory Landscape Of Multiple Stem Cell Compartments During Mammalian Aging, Ling Liu, Soochi Kim, Matthew T Buckley, Jaime M Reyes, Jengmin Kang, Lei Tian, Mingqiang Wang, Alexander Lieu, Michelle Mao, Cristina Rodriguez-Mateo, Heather D Ishak, Mira Jeong, Joseph C Wu, Margaret A Goodell, Anne Brunet, Thomas A Rando

Faculty, Staff and Students Publications

Exercise has the ability to rejuvenate stem cells and improve tissue regeneration in aging animals. However, the cellular and molecular changes elicited by exercise have not been systematically studied across a broad range of cell types in stem cell compartments. We subjected young and old mice to aerobic exercise and generated a single-cell transcriptomic atlas of muscle, neural, and hematopoietic stem cells with their niche cells and progeny, complemented by whole transcriptome analysis of single myofibers. We found that exercise ameliorated the upregulation of a number of inflammatory pathways associated with old age and restored aspects of intercellular communication mediated …

Interspecies Interactions Within The Host: The Social Network Of Group B Streptococcus, Marlyd E Mejia, Clare M Robertson, Kathryn A Patras

Faculty, Staff and Students Publications

Group B Streptococcus (GBS) is a pervasive neonatal pathogen accounting for a combined half a million deaths and stillbirths annually. The most common source of fetal or neonatal GBS exposure is the maternal microbiota. GBS asymptomatically colonizes the gastrointestinal and vaginal mucosa of 1 in 5 individuals globally, although its precise role in these niches is not well understood. To prevent vertical transmission, broad-spectrum antibiotics are administered to GBS-positive mothers during labor in many countries. Although antibiotics have significantly reduced GBS early-onset neonatal disease, there are several unintended consequences, including an altered neonatal microbiota and increased risk for other microbial …

The Sars-Cov-2 Utr’S Intrudes Host Rbp’S And Modulates Cellular Splicing, Anjali Singh, Kush Kumar Pandey, Shubham Kumar Agrawal, Rupesh K. Srivastava, Sankar Bhattacharyya, Bhupendra Verma

Nebraska Center for Virology: Faculty Publications

SARS-CoV-2 is a novel coronavirus that causes a potentially fatal respiratory disease known as coronavirus disease (COVID-19) and is responsible for the ongoing pandemic with increasing mortality. Understanding the host-virus interaction involved in SARS-CoV-2 pathophysiology will enhance our understanding of the mechanistic basis of COVID-19 infection. The characterization of post-transcriptional gene regulatory networks, particularly pre-mRNA splicing, and the identification and characterization of host proteins interacting with the 5' and 3'UTRs of SARS-CoV-2 will improve our understanding of posttranscriptional gene regulation during SARS-CoV-2 pathogenesis. Here, we demonstrate that either SARS-CoV-2 infection or exogenous overexpression of the 5' and 3’UTRs of the …

Application Of A Novel Lytic Jerseyvirus Phage Lpsent1 For The Biological Control Of The Multidrug-Resistant Salmonella Enteritidis In Foods, Rashad R. Al-Hindi, Mona G. Alharbi, Ibrahim Alotibi, Sheren A. Azhari, Khloud M. Algothmi, Ahmed Esmael

Nebraska Center for Virology: Faculty Publications

Non-typhoidal Salmonella is the tremendously predominant source of acquired foodborne infection in humans, causing salmonellosis which is a global threat to the healthcare system. This threat is even worse when it is combined with the incidence of multidrug-resistant Salmonella strains. Bacteriophage therapy has been proposed as a promising potential candidate to control a diversity of foodborne infective bacteria. The objective of this study designed to isolate and characterize lytic phages infecting zoonotic multi-drug resistant and strong biofilm producer Salmonella enterica serovar Enteritidis EG.SmE1 and then apply the isolated phage/s as a biocontrol agent against infections in ready-to-eat food articles including …

Fresh Produce As A Potential Vector And Reservoir For Human Bacterial Pathogens: Revealing The Ambiguity Of Interaction And Transmission, Ahmed Esmael, Rashad R. Al-Hindi, Raed S. Albiheyri, Mona G. Alharbi, Amani A. R. Filimban, Mazen S. Alseghayer, Abdulaziz M. Almaneea, Meshari Ahmed Alhadlaq, Jumaa Ayubu, Addisu D. Teklemariam

Nebraska Center for Virology: Faculty Publications

The consumer demand for fresh produce (vegetables and fruits) has considerably increased since the 1980s for more nutritious foods and healthier life practices, particularly in developed countries. Currently, several foodborne outbreaks have been linked to fresh produce. The global rise in fresh produce associated with human infections may be due to the use of wastewater or any contaminated water for the cultivation of fruits and vegetables, the firm attachment of the foodborne pathogens on the plant surface, and the internalization of these agents deep inside the tissue of the plant, poor disinfection practices and human consumption of raw fresh produce. …

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, Gimenez-Lirola Baum, Locke A. Karriker

Nebraska Center for Virology: 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 …

Was Kaposi’S Sarcoma-Associated Herpesvirus Introduced Into China Via The Ancient Silk Road? An Evolutionary Perspective, Zhenqiu Liu, Qiwen Fang, Jialu Zuo, Veenu Minhas, Charles Wood, Na He, Tiejun Zhang

Nebraska Center for Virology: Faculty Publications

Kaposi’s sarcoma-associated herpesvirus (KSHV) has become widely dispersed worldwide since it was first reported in 1994, but the seroprevalence of KSHV varies geographically. KSHV is relatively ubiquitous in Mediterranean areas and the Xinjiang Uygur Autonomous Region, China. The origin of KSHV has long been puzzling. In the present study, we collected and analysed 154 KSHV ORF-K1 sequences obtained from samples originating from Xinjiang, Italy, Greece, Iran and southern Siberia using Bayesian evolutionary analysis in BEAST to test the hypothesis that KSHV was introduced into Xinjiang via the ancient Silk Road. According to the phylogenetic analysis, 72 sequences were subtype A …

Acute High-Fat Diet Impairs Macrophage-Supported Intestinal Damage Resolution, Andrea A Hill, Myunghoo Kim, Daniel F Zegarra-Ruiz, Lin-Chun Chang, Kendra Norwood, Adrien Assié, Wan-Jung H Wu, Michael C Renfroe, Hyo Wong Song, Angela M Major, Buck S Samuel, Joseph M Hyser, Randy S Longman, Gretchen E Diehl

Faculty, Staff and Students Publications

Chronic exposure to high-fat diets (HFD) worsens intestinal disease pathology, but acute effects of HFD in tissue damage remain unclear. Here, we used short-term HFD feeding in a model of intestinal injury and found sustained damage with increased cecal dead neutrophil accumulation, along with dietary lipid accumulation. Neutrophil depletion rescued enhanced pathology. Macrophages from HFD-treated mice showed reduced capacity to engulf dead neutrophils. Macrophage clearance of dead neutrophils activates critical barrier repair and antiinflammatory pathways, including IL-10, which was lost after acute HFD feeding and intestinal injury. IL-10 overexpression restored intestinal repair after HFD feeding and intestinal injury. Macrophage exposure …

Severe Acute Respiratory Syndrome Coronavirus 2 (Sars-Cov-2) Testing And Detection During Peripartum Hospitalizations Among A Multicenter Cohort Of Pregnant Persons: March 2020-February 2021, Miranda J Delahoy, Flor Munoz, De-Kun Li, Carmen Sofia Arriola, Nanette Lee Bond, Michael Daugherty, Jeannette Ferber, Nickolas Ferguson, Louise Hadden, Jillian T Henderson, Stephanie A Irving, Mary Juergens, Venkatesh Kancharla, Mara Greenberg, Roxana Odouli, Gabriella Newes-Adeyi, Erin G Nicholson, Lawrence Reichle, Momodou Sanyang, Margaret Snead, Fatimah S Dawood, Allison L Naleway

Faculty, Staff and Students Publications

BACKGROUND: Identifying severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections during peripartum hospitalizations is important to guide care, implement prevention measures, and understand infection burden.

METHODS: This cross-sectional analysis used electronic health record data from hospitalizations during which pregnancies ended (peripartum hospitalizations) among a cohort of pregnant persons at 3 US integrated healthcare networks (sites 1-3). Maternal demographic, medical encounter, SARS-CoV-2 testing, and pregnancy and neonatal outcome information was extracted for persons with estimated delivery and pregnancy end dates during March 2020-February 2021 and ≥1 antenatal care record. Site-stratified multivariable logistic regression was used to identify factors associated with testing …

Broad Protective Vaccination Against Systemic Escherichia Coli With Autotransporter Antigens, Yikun Xing, Justin R Clark, James D Chang, Dylan M Chirman, Sabrina Green, Jacob J Zulk, Joseph Jelinski, Kathryn A Patras, Anthony W Maresso

Faculty, Staff and Students Publications

Extraintestinal pathogenic Escherichia coli (ExPEC) is the leading cause of adult life-threatening sepsis and urinary tract infections (UTI). The emergence and spread of multidrug-resistant (MDR) ExPEC strains result in a considerable amount of treatment failure and hospitalization costs, and contribute to the spread of drug resistance amongst the human microbiome. Thus, an effective vaccine against ExPEC would reduce morbidity and mortality and possibly decrease carriage in healthy or diseased populations. A comparative genomic analysis demonstrated a gene encoding an invasin-like protein, termed sinH, annotated as an autotransporter protein, shows high prevalence in various invasive ExPEC phylogroups, especially those associated with …

Displaying And Delivering Viral Membrane Antigens Via Ww Domain–Activated Extracellular Vesicles, Sengjin Choi, Zhiping Yang, Qiyu Wang, Zhi Qiao, Maoyun Sun, Joshua Wiggins, Shi-Hua Xiang, Quan Lu

Nebraska Center for Virology: Faculty Publications

Membrane proteins expressed on the surface of enveloped viruses are conformational antigens readily recognized by B cells of the immune system. An effective vaccine would require the synthesis and delivery of these native conformational antigens in lipid membranes that preserve specific epitope structures. We have created an extracellular vesicle–based technology that allows viral membrane antigens to be selectively recruited onto the surface of WW domain–activated extracellular vesicles (WAEVs). Budding of WAEVs requires secretory carrier-associated membrane protein 3, which through its proline-proline-alanine-tyrosine motif interacts with WW domains to recruit fused viral membrane antigens onto WAEVs. Immunization with influenza and HIV viral …

Displaying And Delivering Viral Membrane Antigens Via Ww Domain–Activated Extracellular Vesicles, Sengjin Choi, Zhiping Yang, Qiyu Wang, Zhi Qiao, Maoyun Sun, Joshua Wiggins, Shi-Hua Xiang, Quan Lu

Nebraska Center for Virology: Faculty Publications

Membrane proteins expressed on the surface of enveloped viruses are conformational antigens readily recognized by B cells of the immune system. An effective vaccine would require the synthesis and delivery of these native conformational antigens in lipid membranes that preserve specific epitope structures. We have created an extracellular vesicle–based technology that allows viral membrane antigens to be selectively recruited onto the surface of WW domain–activated extracellular vesicles (WAEVs). Budding of WAEVs requires secretory carrier-associated membrane protein 3, which through its proline-proline-alanine-tyrosine motif interacts with WW domains to recruit fused viral membrane antigens onto WAEVs. Immunization with influenza and HIV viral …

Baloxavir Safety And Clinical And Virologic Outcomes In Influenza Virus-Infected Pediatric Patients By Age Group: Age-Based Pooled Analysis Of Two Pediatric Studies Conducted In Japan, Nobuo Hirotsu, Hiroki Sakaguchi, Keita Fukao, Satoshi Kojima, Pedro A Piedra, Kenji Tsuchiya, Takeki Uehara

Faculty, Staff and Students Publications

BACKGROUND: Anti-influenza treatment is important for children and is recommended in many countries. This study assessed safety, clinical, and virologic outcomes of baloxavir marboxil (baloxavir) treatment in children based on age and influenza virus type/subtype.

METHODS: This was a post hoc pooled analysis of two open-label non-controlled studies of a single weight-based oral dose of baloxavir (day 1) in influenza virus-infected Japanese patients aged < 6 years (n = 56) and ≥ 6 to < 12 years (n = 81). Safety, time to illness alleviation (TTIA), time to resolution of fever (TTRF), recurrence of influenza illness symptoms and fever (after day 4), virus titer, and outcomes by polymerase acidic protein variants at position I38 (PA/I38X) were evaluated.

RESULTS: Adverse events were reported in 39.0 and 39.5% of patients < 6 years and ≥ 6 to < 12 years, respectively. Median (95% confidence interval) TTIA was 43.2 (36.3-68.4) and 45.4 (38.9-61.0) hours, and TTRF was 32.2 (26.8-37.8) and 20.7 (19.2-23.8) hours, for patients < 6 years and ≥ 6 to < 12 years, respectively. Symptom and fever recurrence was more common in patients < 6 years with influenza B (54.5 and 50.0%, respectively) compared with older patients (0 and 25.0%, respectively). Virus titers declined (day 2) for both age groups. Transient virus titer increase and PA/I38X-variants were more common for patients < 6 years.

CONCLUSIONS: The safety and effectiveness of single-dose baloxavir were observed in children across all age groups and influenza virus types. Higher rates of fever recurrence …

Differential Co-Expression Networks Of The Gut Microbiota Are Associated With Depression And Anxiety Treatment Resistance Among Psychiatric Inpatients, Dominique S Thompson, Chenlian Fu, Tanmay Gandhi, J Christopher Fowler, B Christopher Frueh, Benjamin L Weinstein, Joseph Petrosino, Julia K Hadden, Marianne Carlson, Cristian Coarfa, Alok Madan

Faculty, Staff and Students Publications

BACKGROUND: Comorbid anxiety and depression are common and are associated with greater disease burden than either alone. Our recent efforts have identified an association between gut microbiota dysfunction and severity of anxiety and depression. In this follow-up, we applied Differential Co-Expression Analysis (DiffCoEx) to identify potential gut microbiota biomarker(s) candidates of treatment resistance among psychiatric inpatients.

METHODS: In a sample of convenience, 100 psychiatric inpatients provided clinical data at admission and discharge; fecal samples were collected early during the hospitalization. Whole genome shotgun sequencing methods were used to process samples. DiffCoEx was used to identify clusters of microbial features significantly …

Early-Phase Drive To The Precursor Pool: Chloroviruses Dive Into The Deep End Of Nucleotide Metabolism, David Dunigan, Irina Agarkova, Ahmed Esmael, Sophie Alvarez, James L. Van Etten

Nebraska Center for Virology: Faculty Publications

Viruses face many challenges on their road to successful replication, and they meet those challenges by reprogramming the intracellular environment. Two major issues challenging Paramecium bursaria chlorella virus 1 (PBCV-1, genus Chlorovirus, family Phycodnaviridae) at the level of DNA replication are (i) the host cell has a DNA G+C content of 66%, while the virus is 40%; and (ii) the initial quantity of DNA in the haploid host cell is approximately 50 fg, yet the virus will make approximately 350 fg of DNA within hours of infection to produce approximately 1000 virions per cell. Thus, the quality and quantity of …

The Persistence And Stabilization Of Auxiliary Genes In The Human Skin Virome, Ema H. Graham, Wesley A. Tom, Alison C. Neujahr, Michael Adamowicz, Jennifer Clarke, Joshua R. Herr, Samodha C. Fernando

Nebraska Center for Virology: Faculty Publications

Background The human skin contains a diverse microbiome that provides protective functions against environmental pathogens. Studies have demonstrated that bacteriophages modulate bacterial community composition and facilitate the transfer of host-specific genes, potentially influencing host cellular functions. However, little is known about the human skin virome and its role in human health. Especially, how viral-host relationships influence skin microbiome structure and function is poorly understood.

Results Population dynamics and genetic diversity of bacteriophage communities in viral metagenomic data collected from three anatomical skin locations from 60 subjects at five different time points revealed that cutaneous bacteriophage populations are mainly composed of …

Proposing An Rna Interference (Rnai)-Based Treatment For Human Immunodeficiency Virus (Hiv) By Analyzing The Post-Transcriptional Gene Targeting Of Sars-Cov-2, Hepatitis C Virus, And A549 Lung Cancer Cells, Arjun Jagdeesh

Undergraduate Research Posters

Human Immunodeficiency Virus (HIV) is a retrovirus that infects CD4+ T cell lymphocytes in humans, leading to the development of Acquired Immunodeficiency Syndrome (AIDS) if left untreated. While current treatment methods, including antiretroviral combination treatments, effectively limit HIV replication, HIV can evade these treatments due to its high mutation rate. Long-term antiretroviral treatment can also be toxic to patients, meaning patients would benefit from a new mechanism of HIV treatment. RNA interference (RNAi) is an antiviral pathway found in mammals, plants, and insects that involves a small-interfering RNA that is incorporated into a protein complex called the RNA-induced Silencing Complex …

The Small Intestinal Microbiome: Vibing With Intestinal Stem Cells, Victoria Poplaski, Faith Sawyer, Sarah E Blutt

Faculty, Staff and Students Publications

The epithelial lining of the small intestine mediates its absorptive and secretory function and thus is a critical component of human health. Regeneration and renewal of the epithelium is the result of proliferation of intestinal stem cells (ISCs). Many cell types and molecular factors are known to regulate the ability of ISCs to proliferate, including adjacent neighboring epithelial cells and the underlying, supportive stromal cells. The microbiome resides in the lumen of the small intestine and is in close contact with the epithelium. Due to its proximity to ISCs, it has been hypothesized that species within the microbiome have the …

The Rsv F P27 Peptide: Current Knowledge, Important Questions, Wanderson Rezende, Hadley E Neal, Rebecca E Dutch, Pedro A Piedra

Faculty, Staff and Students Publications

Respiratory syncytial virus (RSV) remains a leading cause of hospitalizations and death for young children and adults over 65. The worldwide impact of RSV has prioritized the search for an RSV vaccine, with most targeting the critical fusion (F) protein. However, questions remain about the mechanism of RSV entry and RSV F triggering and fusion promotion. This review highlights these questions, specifically those surrounding a cleaved 27 amino acids long peptide within F, p27.

Diversity And Evolution Of Computationally Predicted T Cell Epitopes Against Human Respiratory Syncytial Virus, Jiani Chen, Swan Tan, Vasanthi Avadhanula, Leonard Moise, Pedro A Piedra, Anne S De Groot, Justin Bahl

Faculty, Staff and Students Publications

Human respiratory syncytial virus (RSV) is a major cause of lower respiratory infection. Despite more than 60 years of research, there is no licensed vaccine. While B cell response is a major focus for vaccine design, the T cell epitope profile of RSV is also important for vaccine development. Here, we computationally predicted putative T cell epitopes in the Fusion protein (F) and Glycoprotein (G) of RSV wild circulating strains by predicting Major Histocompatibility Complex (MHC) class I and class II binding affinity. We limited our inferences to conserved epitopes in both F and G proteins that have been experimentally …

A Monovalent Mt10-Cvb3 Vaccine Prevents Cvb4-Accelerated Type 1 Diabetes In Nod Mice, Mahima T. Rasquinha, Ninaad Lasrado, Meghna Sur, Kiruthiga Mone, Haowen Qiu, Jean-Jack Riethoven, Raymond A. Sobel, Jay Reddy

Nebraska Center for Virology: Faculty Publications

Enteroviruses, which include Coxsackieviruses, are a common cause of virus infections in humans, and multiple serotypes of the group B Coxsackievirus (CVB) can induce similar diseases. No vaccines are currently available to prevent CVB infections because developing serotype-specific vaccines is not practical. Thus, developing a vaccine that induces protective immune responses for multiple serotypes is desired. In that direction, we created a live-attenuated CVB3 vaccine virus, designated mutant (Mt)10, that offers protection against myocarditis and pancreatitis induced by CVB3 and CVB4 in disease-susceptible A/J mice. Here, we report that the Mt10 vaccine protected against CVB4-triggered type 1 diabetes (T1D) in …

Surveillance Of Antimicrobial Resistance In Veterinary Medicine In The United States: Current E, Juliana M. Ruzante, Beth Harris, Paul Plummer, Raissa R. Raineri, John Dustin Loy, Megan Jacob, Orhan Sahin, Amanda J. Kreuder

Nebraska Center for Virology: Faculty Publications

Antimicrobial resistance (AMR) is a global problem facing human, animal, plant, and environmental health by threatening our ability to effectively treat bacterial infections with antimicrobials. In the United States, robust surveillance efforts exist to collect, analyze, and disseminate AMR data in human health care settings. These tools enable the development of effective infection control methods, the detection of trends, and provide the evidence needed to guide stewardship efforts to reduce the potential for emergence and further spread of AMR. However, in veterinary medicine, there are currently no known equivalent tools. This paper reviews efforts to reduce the potential for emergence …

Genotype Classification Of Moraxella Bovis Using Maldi-Tof Ms Profiles, Hannah G. Olson, John Dustin Loy, Michael L. Clawson, Emily L. Wynn, Matthew M. Hille

Nebraska Center for Virology: Faculty Publications

Moraxella bovis (M. bovis) is regarded as a causative agent of infectious bovine keratoconjunctivitis (IBK), the most common ocular disease of cattle. Recently, whole genome sequencing identified the presence of two distinct genotypes within M. bovis that differ in chromosome content, potential virulence factors, as well as prophage and plasmid profiles. It is unclear if the genotypes equally associate with IBK or if one is more likely to be isolated from IBK lesions. We utilized 39 strains of M. bovis that had previously undergone whole genome sequencing and genotype classification to determine the utility of matrix-assisted laser desorption/ionization …

Isolation And Characterization Of Chi-Like Salmonella Bacteriophages Infecting Two Salmonella Enterica Serovars, Typhimurium And Enteritidis, Addisu D. Teklemariam, Mona G. Alharbi, Rashad R. Al-Hindi, Ibrahim Alotibi, Abdullah A. Aljaddawi, Sheren A. Azhari, Ahmed Esmael

Nebraska Center for Virology: Faculty Publications

Salmonella enterica Serovar Typhimurium and Salmonella enterica Serovar Enteritidis are well-known pathogens that cause foodborne diseases in humans. The emergence of antibiotic-resistant Salmonella serovars has caused serious public health problems worldwide. In this study, two lysogenic phages, STP11 and SEP13, were isolated from a wastewater treatment plant in Jeddah, KSA. Transmission electron microscopic images revealed that both phages are new members of the genus “Chivirus” within the family Siphoviridae. Both STP11 and SEP13 had a lysis time of 90 min with burst sizes of 176 and 170 PFU/cell, respectively. The two phages were thermostable (0 ^◦C …

The Mechanisms Of Mitochondrial Dysfunction In T Cell Aging During Chronic Viral Infection, Madison B. Schank

Electronic Theses and Dissertations

Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections induce a myriad of disturbances to CD4 T cell functions, including mitochondrial compromise, excessive inflammation, increased telomeric DNA damage and attrition, cellular exhaustion and senescence, and accelerated aging. In this dissertation, the mechanisms underlying metabolic failure, accelerated aging, and cellular dysfunctions were evaluated in CD4 T cells from healthy subjects (HS) treated with a telomere-targeting drug (KML001) or HCV-infected individuals or people living with HIV (PLHIV) compared to HS. We observed that KML001-induced telomere injury resulted in mitochondrial swelling and decreased mitochondrial membrane potential, cellular respiration, mitochondrial DNA (mtDNA) copy …

T-Cell Antigen Receptors In Multiple Sclerosis, Lisa Lanée Keyes Jones

Biomedical Sciences Theses & Dissertations

Multiple Sclerosis (MS) is T-cell mediated autoimmune disease characterized by inflammation, demyelination, and degeneration of axons in the brain and spinal cord. A T cell-mediated immune response in MS is directed against myelin components and possibly other antigens in genetically susceptible individuals and is triggered by a viral infection. The T-cell antigen receptor (TCR) on T cells is responsible for antigen recognition and determines specificity. Our overall hypothesis is to determine whether clonally expanded T cells in patients with MS recognize viral or self-antigens and to determine whether molecular mimicry is involved in the development of the disease. To study …

Investigating The Pi3k/Akt/Atm Pathway, Telomeric Dna Damage, T Cell Death, And Crispr/Cas9-Mediated Gene Editing During Acute And Chronic Hiv Infection, Sushant Khanal

Electronic Theses and Dissertations

Human Immunodeficiency Virus (HIV) infection initiates major metabolic and cell- survival complications. Anti-retroviral therapy (ART) is the current approach to suppress active HIV replication to a level of undetected viral load, but it is not a curative approach. Newer and sophisticated gene editing technologies could indeed be a potent antiviral therapy to achieve a clinical sterilization/cure of HIV infection. Chronic HIV patients, even under a successful ART regimen, exhibit a low-grade inflammation, immune senescence, premature aging, telomeric DNA attrition, T cell apoptosis, and cellular homeostasis. In this dissertation, we investigated CD4 T cell homeostasis, degree of T cell apoptosis, an …

Loss Of Wnt4 In The Gubernaculum Causes Unilateral Cryptorchidism And Fertility Defects, Abhishek Seth, Juan C Bournat, Olga Medina-Martinez, Armando Rivera, Joshua Moore, Hunter Flores, Jill A Rosenfeld, Liya Hu, Carolina J Jorgez

Faculty, Staff and Students Publications

Undescended testis (UDT) affects 6% of male births. Despite surgical correction, some men with unilateral UDT may experience infertility with the contralateral descended testis (CDT) showing no A-dark spermatogonia. To improve our understanding of the etiology of infertility in UDT, we generated a novel murine model of left unilateral UDT. Gubernaculum-specific Wnt4 knockout (KO) mice (Wnt4-cKO) were generated using retinoic acid receptor β2-cre mice and were found to have a smaller left-unilateral UDT. Wnt4-cKO mice with abdominal UDT had an increase in serum follicle-stimulating hormone and luteinizing hormone and an absence of germ cells in the undescended testicle. Wnt4-cKO mice …