Virology Commons^™

Characterization Of The Role Of The Replicase And Quasispecies Diversity In Flaviviral Evolution And Host Adaptation, Haley Caldwell

Legacy Theses & Dissertations (2009 - 2024)

Flaviviruses include several emerging and re-emerging arboviruses that cause millions of infections each year. Although relatively well-studied, much remains unknown regarding the mechanisms and means by which these viruses adapt to different hosts and rapidly alternate between hosts. Different aspects of flaviviral biology impact host switching, viral fitness, and the generation of viral diversity during genome replication by the NS3 and NS5 proteins. Together these factors may impact host plasticity.

Mathematical Modeling Of Potassium Modulated Viral Infection, Zaira Elizabeth Mather

Open Access Theses & Dissertations

In recent years, there is a growing interest in the investigation of using potassium to treat virus infections. In the region of infection, there is a biological observation of extracel- lular potassium level being typically very low whereas the intracellular potassium levels are much higher. There are numerous biological studies showing that elevated potassium levels in the extracellular membrane tends to block virus infections. A recent effort in this direction is a collaborative research conducted by mathematicians and biologists from the University of Texas at El Paso, New Mexico State University, and the University of New Mexico, where we develop …

Antiviral Activity Of Olanexidine-Containing Hand Rub Against Human Noroviruses, Khalil Ettayebi, Wilhelm Salmen, Kaoru Imai, Akifumi Hagi, Frederick H Neill, Robert L Atmar, B V Venkataram Prasad, Mary K Estes

Faculty, Staff and Students Publications

Human norovirus (HuNoV) is the leading cause of epidemic and sporadic acute gastroenteritis worldwide. HuNoV transmission occurs predominantly by direct person-to-person contact, and its health burden is associated with poor hand hygiene and a lack of effective antiseptics and disinfectants. Specific therapies and methods to prevent and control HuNoV spread previously were difficult to evaluate because of the lack of a cell culture system to propagate infectious virus. This barrier has been overcome with the successful cultivation of HuNoV in nontransformed human intestinal enteroids (HIEs). Here, we report using the HIE cultivation system to evaluate the virucidal efficacy of an …

Evaluation Of Protective Efficacy Of Viral Vector Based Swine Influenza Vaccine And A Method For B Cell Culture For Monoclonal Antibody Generation, Sushmita Kumari

School of Veterinary and Biomedical Sciences: Dissertations, Theses, and Student Research

Influenza A virus of the swine (IAV-S) is an economically important swine pathogen that has the potential to spread to humans, thus posing an ongoing public health concern due to its zoonotic potential. Hemagglutinin (HA), the most abundant viral envelope protein, is known to be the key protective antigen. Anti-HA antibodies alone, have been shown to prevent IAV infection. In this study we evaluated the feasibility of a recombinant tri segmented Pichinde virus (PICV) as a viral vector to deliver IAV-S hemagglutinin antigen in pigs. Four groups of weaned pigs (T01-04) were immunized twice with PBS, rPICV-GFP as a vector …

Sars-Cov-2 Reveals That Chimeric Agents Are The Bioweapons Of The Future, Rachel Craig

Senior Honors Theses

Bioweapons programs have existed since their development during the Cold War. These biowarfare programs initially utilized naturally occurring pathogens capable of infecting crops, livestock populations, and human populations. Anthrax is a widely exploited bioagent responsible for attacks ranging from the Germans’ deployment in World War I to the mailing of anthrax through the postal service in attempts on U.S. senators’ lives. With the development of genetic manipulations, the Soviet Union began modifying anthrax to resist detection and treatment. With the continued advancement of science and technology, a new bioagent has entered the scene – the man-made chimeric virus. Chimeric viruses …

Generation Of Crispr-Cas9-Mediated Genetic Knockout Human Intestinal Tissue-Derived Enteroid Lines By Lentivirus Transduction And Single-Cell Cloning, Shih-Ching Lin, Kei Haga, Xi-Lei Zeng, Mary K Estes

Faculty, Staff and Students Publications

Human intestinal tissue-derived enteroids (HIEs; also called organoids) are a powerful ex vivo model for gastrointestinal research. Genetic modification of these nontransformed cultures allows new insights into gene function and biological processes involved in intestinal diseases as well as gastrointestinal and donor segment-specific function. Here we provide a detailed technical pipeline and protocol for using the CRISPR-Cas9 genome editing system to knock out a gene of interest specifically in HIEs by lentiviral transduction and single-cell cloning. This protocol differs from a previously published alternative using electroporation of human colonoids to deliver piggyback transposons or CRISPR-Cas9 constructs, as this protocol uses …

A Quantitative Analysis Of The Efficacy Of Various Essential Oils Against The Sars Cov-2 Virus, Elizabeth Wagstaff, Chandrelyn Kraczek, Jack Brandon Lopez

Annual Research Symposium

A poster presentation and abstract for the Roseman Symposium. The project focuses on testing 3 essential oil blends and two disinfectants containing an essential oil blend against SARS CoV-2 in response to the COVID-19 pandemic. The project procedure involves plaque assays, disinfection, and neutralization techniques.

Meta-Analysis Of Transcriptomic Datasets For The Investigation Of Differential Expression In Hantavirus-Infected Human Tissue, John Krapohl

Annual Research Symposium

No abstract provided.

Gut-Derived Butyrate Suppresses Ocular Surface Inflammation, Laura Schaefer, Humberto Hernandez, Rosalind A Coats, Zhiyuan Yu, Stephen C Pflugfelder, Robert A Britton, Cintia S De Paiva

Faculty, Staff and Students Publications

Dry eye is a common ocular inflammatory disorder characterized by tear film instability and reduced tear production. There is increasing evidence that homeostasis of the ocular surface is impacted by the intestinal microbiome. We are interested in investigating the potential role of microbially produced small molecules in mediating the interaction between the intestinal microbiota and the ocular surface. One such molecule is butyrate, a short-chain fatty acid (SCFA) produced by certain members of the gut microbiota through fermentation of dietary fiber. Here we show that SCFA transporter SLC5A8 is expressed in vivo in murine conjunctival and corneal epithelium. Pre-treatment of …

Considerations For The Use Of Phage Therapy In Clinical Practice, Gina A Suh, Thomas P Lodise, Pranita D Tamma, Jane M Knisely, Jose Alexander, Saima Aslam, Karen D Barton, Erica Bizzell, Katherine M C Totten, Joseph L Campbell, Benjamin K Chan, Scott A Cunningham, Katherine E Goodman, Kerryl E Greenwood-Quaintance, Anthony D Harris, Shayla Hesse, Anthony Maresso, Veronique Nussenblatt, David Pride, Michael J Rybak, Zoe Sund, David Van Duin, Daria Van Tyne, Robin Patel

Faculty, Staff and Students Publications

Increasing antimicrobial resistance and medical device-related infections have led to a renewed interest in phage therapy as an alternative or adjunct to conventional antimicrobials. Expanded access and compassionate use cases have risen exponentially but have varied widely in approach, methodology, and clinical situations in which phage therapy might be considered. Large gaps in knowledge contribute to heterogeneity in approach and lack of consensus in many important clinical areas. The Antibacterial Resistance Leadership Group (ARLG) has convened a panel of experts in phage therapy, clinical microbiology, infectious diseases, and pharmacology, who worked with regulatory experts and a funding agency to identify …

Identifying Causative Microorganisms In Left Ventricular Assist Device Infections As A Guide For Developing Bacteriophage Therapy, Ishan Kamat, Harveen Lamba, Casey Hines-Munson, Samuel Hudson, Kenneth Liao, Kenneth L Muldrew, Sabrina Green, Austen Terwilliger, Heidi B Kaplan, Robert F Ramig, Anthony Maresso, Barbara W Trautner

Faculty, Staff and Students Publications

BACKGROUND: As more left ventricular-assist devices (LVADs) are implanted, multidrug-resistant LVAD infections are becoming increasingly common, partly due to bacterial biofilm production. To aid in developing bacteriophage therapy for LVAD infections, we have identified the most common bacterial pathogens that cause LVAD driveline infections (DLIs) in our heart transplant referral center.

MATERIALS AND METHODS: We studied a retrospective cohort of patients who received LVADs from November 2003 to August 2017 to identify the common causative organisms of LVAD infection. We also studied a prospective cohort of patients diagnosed with DLIs from October 2018 to May 2019 to collect bacterial strains …

Fully Resolved Assembly Of Cryptosporidium Parvum, Vipin K Menon, Pablo C Okhuysen, Cynthia L Chappell, Medhat Mahmoud, Medhat Mahmoud, Qingchang Meng, Harsha Doddapaneni, Vanesa Vee, Yi Han, Sejal Salvi, Sravya Bhamidipati, Kavya Kottapalli, George Weissenberger, Hua Shen, Matthew C Ross, Kristi L Hoffman, Sara Javornik Cregeen, Donna M Muzny, Ginger A Metcalf, Richard A Gibbs, Joseph F Petrosino, Fritz J Sedlazeck

Faculty, Staff and Students Publications

BACKGROUND: Cryptosporidium parvum is an apicomplexan parasite commonly found across many host species with a global infection prevalence in human populations of 7.6%. Understanding its diversity and genomic makeup can help in fighting established infections and prohibiting further transmission. The basis of every genomic study is a high-quality reference genome that has continuity and completeness, thus enabling comprehensive comparative studies.

FINDINGS: Here, we provide a highly accurate and complete reference genome of Cryptosporidium parvum. The assembly is based on Oxford Nanopore reads and was improved using Illumina reads for error correction. We also outline how to evaluate and choose from …

Reducing Influenza Virus Transmission: The Potential Value Of Antiviral Treatment, Frederick G Hayden, Jason Asher, Benjamin J Cowling, Aeron C Hurt, Hideyuki Ikematsu, Klaus Kuhlbusch, Annabelle Lemenuel-Diot, Zhanwei Du, Lauren Ancel Meyers, Pedro A Piedra, Takahiro Takazono, Hui-Ling Yen, Arnold S Monto

Faculty, Staff and Students Publications

Prompt antiviral treatment has the potential to reduce influenza virus transmission to close contacts, but rigorous data on the magnitude of treatment effects on transmission are limited. Animal model data indicate that rapid reductions in viral replication after antiviral treatment reduce the risk of transmission. Observational and clinical trial data with oseltamivir and other neuraminidase inhibitors indicate that prompt treatment of household index patients seems to reduce the risk of illness in contacts, although the magnitude of the reported effects has varied widely across studies. In addition, the potential risk of transmitting drug-resistant variants exists with all approved classes of …

Depletion Of The Apical Endosome In Response To Viruses And Bacterial Toxins Provides Cell-Autonomous Host Defense At Mucosal Surfaces, Keiko Maeda, Nicholas C Zachos, Megan H Orzalli, Stefanie S Schmieder, Denis Chang, Katlynn Bugda Gwilt, Michele Doucet, Nicholas W Baetz, Sun Lee, Sue E Crawford, Mary K Estes, Jonathan C Kagan, Jerrold R Turner, Wayne I Lencer

Faculty, Staff and Students Publications

Polarized epithelial cells form an essential barrier against infection at mucosal surfaces. Many pathogens breach this barrier to cause disease, often by co-opting cellular endocytosis mechanisms to enter the cell through the lumenal (apical) cell surface. We recently discovered that the loss of the cell polarity gene PARD6B selectively diminishes apical endosome function. Here, we find that in response to the entry of certain viruses and bacterial toxins into the epithelial cells via the apical membrane, PARD6B and aPKC, two components of the PARD6B-aPKC-Cdc42 apical polarity complex, undergo rapid proteasome-dependent degradation. The perturbation of apical membrane glycosphingolipids by toxin- or …

Age-Associated Gut Dysbiosis, Marked By Loss Of Butyrogenic Potential, Correlates With Altered Plasma Tryptophan Metabolites In Older People Living With Hiv, Smita Ghare, Richa Singhal, Vaughn Bryant, Sabina Gautam, Chanakya Charan Tirumala, Praneet Kumar Srisailam, Andrea Reyes-Vega, Dushan Ghooray, Craig J Mcclain, Kristi Hoffman, Joseph Petrosino, Kendall Bryant, Varan Govind, Ronald Cohen, Robert L Cook, Shirish Barve

Faculty, Staff and Students Publications

BACKGROUND: Imbalance in tryptophan (TRP) metabolism and its neuroactive metabolites, serotonin and kynurenine (KYN), is a known pathogenic mechanism underlying neurocognitive impairment. Gut microbiota plays an important role in TRP metabolism, and the production of these neuroactive molecules affects neurocognitive function. Although both HIV infection and normal aging independently induce gut dysbiosis and influence TRP metabolism, their interactive effects on compositional/functional changes in gut microbiota and consequent alterations in TRP metabolites remain largely undetermined.

METHODS: Older people living with HIV infection (PLWH, aged 50-70 years, n = 22) were enrolled in this cross-sectional pilot study. Metagenomic analysis of fecal microbiome …

Conformational Flexibility And Local Frustration In The Functional States Of The Sars-Cov-2 Spike B.1.1.7 And B.1.351 Variants: Mutation-Induced Allosteric Modulation Mechanism Of Functional Dynamics And Protein Stability, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

Structural and functional studies of the SARS-CoV-2 spike proteins have recently determined distinct functional states of the B.1.1.7 and B.1.351 spike variants, providing a molecular framework for understanding the mechanisms that link the effect of mutations with the enhanced virus infectivity and transmissibility. A detailed dynamic and energetic analysis of these variants was undertaken in the present work to quantify the effects of different mutations on functional conformational changes and stability of the SARS-CoV-2 spike protein. We employed the efficient and accurate coarse-grained (CG) simulations of multiple functional states of the D614G mutant, B.1.1.7 and B.1.351 spike variants to characterize …

The Coxsackievirus And Adenovirus Receptor Has A Short Half-Life In Epithelial Cells, Poornima Kotha Lakshmi Narayan, James M. Readler, Mahmoud S. Alghamri, Trisha L. Brockman, Ray Yan, Priyanka Sharma, Vladislav Snitsarev, Katherine J.D.A Excoffon, Abimbola O. Kolawole

Department of Biology Faculty Scholarship and Creative Works

The coxsackievirus and adenovirus receptor (CAR) is an essential cellular protein that is involved in cell adhesion, cell signaling, and viral infection. The 8-exon encoded isoform (CAREx8) resides at the apical surface of polarized epithelia, where it is accessible as a receptor for adenovirus entering the airway lumen. Given its pivotal role in viral infection, it is a target for antiviral strategies. To understand the regulation of CAREx8 and determine the feasibility of receptor down regulation, the half-life of total and apical localized CAREx8 was determined and correlated with adenovirus transduction. Total and apical CAREx8 has a relatively short half-life …

Organoid Models For Infectious Disease, Sarah E Blutt, Mary K Estes

Faculty, Staff and Students Publications

Infectious diseases affect individual health and have widespread societal impacts. New ex vivo models are critical to understand pathogenesis, host response, and features necessary to develop preventive and therapeutic treatments. Pluripotent and tissue stem cell-derived organoids provide new tools for the study of human infections. Organoid models recapitulate many characteristics of in vivo disease and are providing new insights into human respiratory, gastrointestinal, and neuronal host-microbe interactions. Increasing culture complexity by adding the stroma, interorgan communication, and the microbiome will improve the use of organoids as models for infection. Organoid cultures provide a platform with the capability to improve human …

Enteroviruses And Type 1 Diabetes: Multiple Mechanisms And Factors?, Richard E Lloyd, Manasi Tamhankar, Åke Lernmark

Faculty, Staff and Students Publications

Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by insulin deficiency and resultant hyperglycemia. Complex interactions of genetic and environmental factors trigger the onset of autoimmune mechanisms responsible for development of autoimmunity to β cell antigens and subsequent development of T1D. A potential role of virus infections has long been hypothesized, and growing evidence continues to implicate enteroviruses as the most probable triggering viruses. Recent studies have strengthened the association between enteroviruses and development of autoimmunity in T1D patients, potentially through persistent infections. Enterovirus infections may contribute to different stages of disease development. We review data from both …

Phage Hunters: The Discovery Of Two Novel Bacteriophages That Infect Gordonia Rubripertincta, Sarah Ballarin, Neel Balusa, Melissa Bell, Samia Caballero, Joshua Chan, Maria Farez, Ashley J. Guillen-Tapia, Nashrah Pierre-Louis, Victoria Polishuk, Bhavya Soni, Julie Torruellas Garcia, Katie E. Crump

Sea-Phages

Antibiotic resistance is a global healthcare concern because it poses a threat to effectively treating bacterial infections and the need for alternative therapeutics are urgently required. Phage therapy, which uses viruses to treat bacterial infections, is a promising alternative to conventional antibiotics. Phages have also been widely used in the food industry to prevent microbial growth on certain foods and are currently being explored as a method for bioremediation of oil spills and wastewater treatment. Although phages are ubiquitous in nature, many have yet to be discovered. Through the SEA-PHAGES (Science Education Alliance-Phage Hunters Advancing Genomics and Evolutionary Science) program …