Virology Commons^™

Cancer-Specific Perturbations To Arginine Metabolism Blunt Replication And Performance Of Oncolytic Myxoma Virus, Parker Dryja

MUSC Theses and Dissertations

Oncolytic virotherapy (OV) is a class of immunotherapy for treatment of malignancy. Using viruses that exhibit natural coincidental tropisms for cancer, or others that have been engineered to the same effect, intentional infection of lesions leads to two therapeutically beneficial effects: (1) direct destruction of the infected tumor through virally-mediated cell lysis, and (2) recruitment of an otherwise blunted or absent anti-cancer immune response to affect both local and disseminated disease. A surfeit of cancer-specific changes are accumulated during progression from first genetic insult to clinical detection, presenting a dramatically altered underlying biology of cell and tissue. The viruses employed …

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 …

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 …

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. …

Identifying Non-Traditional Slippery Sequences Associated With Translational Frameshifts, Aaron J. Gin, Kari Lynn Clase

Graduate Industrial Research Symposium

Genetic frameshifts are a mutation in which
a nucleotide skip leads to a shift in the
reading frame. In viruses, these frameshifts
can be programmed using a slippery
sequence to bypass the stop codon
associated with the initial protein. This
allows for variable control of protein
expression. In bacteriophages, translational
frameshifts have been identified but only a
few have been proven experimentally. Using
experimental data and comparative
genomics, non-traditional slippery
sequences can be identified as assisting in
controlling the protein coding throughout
viruses. Novel slippery sequences can aid in
the understanding of protein expression in
biological environments and further the …

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 …

Recombinant Protein Vaccines Formulated With Enantio-Specific Cationic Lipid R-Dotap Induce Protective Cellular And Antibody-Mediated Immune Responses In Mice, Siva Gandhapudi, Hua Shi, Martin Ward, John Peyton Bush, Margarita G. Avdiushko, Karuna Sundarapandiyan, Lauren V. Wood, Mania Dorrani, Afsheen Fatima, Joe Dervan, Frank Bedu-Addo, Greg Conn, Ted M. Ross, Jerold Woodward

Markey Cancer Center Faculty Publications

Adjuvants are essential components of subunit vaccines added to enhance immune responses to antigens through immunomodulation. Very few adjuvants have been approved for human use by regulatory agencies due to safety concerns. Current subunit vaccine adjuvants approved for human use are very effective in promoting humoral immune responses but are less effective at promoting T-cell immunity. In this study, we evaluated a novel pure enantio-specific cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (R-DOTAP) as an immunomodulator for subunit vaccines capable of inducing both humoral- and cellular-mediated immunity. Using recombinant protein antigens derived from SARS-CoV2 spike or novel computationally optimized broadly reactive influenza antigen (COBRA) …

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 …

The Immune Modulation On Innate Immunity, From Pathogen Recognition To Fungal Clearance., Ko-Wei Liu

Dartmouth College Ph.D Dissertations

The human lung is not sterile but a complex environment with various microorganisms. Besides commensals in the lung, hundreds to thousands of individual microbiomes enter the lung every day but without causing the symptom. Host innate immunity plays an important role in maintaining homeostasis of the lung environment and as the first defense line against pathogens. Aspergillus fumigatus (A. fumigatus) is a saprophytic filamentous fungus that can cause human disease in immune compromised patients. However, with functional innate immunity, immune cells can quickly recognize pathogen associated molecular patterns (PAMPs) from A. fumigatus through pattern recognition receptors (PRRs). The activation of …

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 …

Receptor Usage And Infection Biology Of Influenza D Virus, Tirth Uprety

Theses and Dissertations--Veterinary Science

Influenza D virus (IDV) utilizes bovines as a primary reservoir with periodical spillover to other hosts. We have previously demonstrated by the traditional hemagglutination assay coupled with sialoglycan microarray and functional assays that IDV can recognize and bind both 9-O-acetylated N-acetylneuraminic acid (Neu5,9Ac₂) and 9-O-acetylated N-glycolylneuraminic acid (Neu5Gc9Ac). Agricultural animals such as cattle can produce both Neu5,9Ac₂ and Neu5Gc9Ac, while humans are genetically unable to synthesize Neu5Gc9Ac. The bifunctional enzyme, glucosamine (UDP-N-acetyl)-2-epimerase/N-acetylmannosamine kinase (GNE) is a master regulator of de-novo sialic acid synthesis while 9-O-Acetylation of sialic acids is catalyzed by …