Virology Commons^™

Developing A Nasal Organotypic Model To Investigate The Effects Of The Nasal Microbiome On Susceptibility To Pathogens, Victor H.K. Lam Mr.

Undergraduate Student Research Internships Conference

The microbiota is essential to the functioning of the immune system. The nasal milieu secretes immune molecules that can be influenced by diverse bacteria. Hence commensals that enhance anti-viral responses may confer resistance to respiratory viral infection.

Our collaborators have identified 7 microbial state types (CST) defined by indicator species in the nose and recently, through analyses of nasal immune molecules, we have categorized the nasal immune profile types into 8 groups (IPT). Although the IPTs correlated with certain CSTs, the influence of the nasal microbiome on susceptibility to respiratory pathogens is still unknown.

Defining this complex relationship requires a …

Functional Characterization Of Mycobacterium Smegmatis Phage Moomoo Gene Products: Identification Of Toxic Genes, Whitney Heard

Masters Theses & Specialist Projects

Mycobacteriophages are a group of phages that infect members of the genus Mycobacteria. Previous studies have conducted extensive comparisons of the mycobacteriophage genomes and amino acid sequences to establish different phage families. MooMoo is a singleton mycobacteriophage that has been characterized due to its lack of appreciable homology to other phages. Some of its unique properties include its structure and the isolation of a mutant that causes clear plaque phenotypes. The experiments described in this thesis identified three MooMoo phage (gp87, gp90, and gp91) encoded proteins that are toxic to the bacterial host, Mycobacterium smegmatis.Through the use of a …

Defining The Importance Of The Hnrnp I Interaction To The Sindbis Virus Subgenomic Viral Rna Using An Innovative Tethering Approach., Claire Westcott

Electronic Theses and Dissertations

Old World alphaviruses cause significant outbreaks of illness and debilitating multi-joint arthritis for prolonged periods. Currently, there are no FDA approved vaccines or antiviral therapies; and thus, there is a critical need to identify and characterize the molecular biology of alphaviruses. Alphaviruses rely on the host cell machinery to complete the viral lifecycle and are dependent on interactions with host RNA binding proteins. Accordingly, several host heterogenous nuclear ribonucleoprotein proteins (hnRNPs) have been found to bind to the Sindbis virus (SINV) RNAs. Disrupting the interaction sites in the viral RNAs of these RNA:Protein interactions results in decreased viral titers in …

Regulation Of Mhc Ii Trafficking And Expression By Host And Viral Factors, Alex Lac

Electronic Thesis and Dissertation Repository

Antigen presentation by major histocompatibility complex class II (MHC II) to the adaptive immune system is crucial for mounting sterilizing immune responses. This central role has made antigen presentation a target for antagonism by many pathogens. Notably, infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) decrease MHC II expression in several immune cells. The mechanisms responsible for this suppression are unknown but involves either redirecting MHC II molecules away from the cell surface or inhibiting MHC II expression. To understand how pathogens manipulate intracellular MHC II trafficking, we first investigated the role of the Golgi trafficking regulator, ERC1, in …

Resolving The Repression Pathway Of Virulence Gene Hila In Salmonella, Alexandra King, Lon Chubiz Phd, Brenda Pratte, Lauren Daugherty

Undergraduate Research Symposium

Salmonella is a relatively abundant, virulent species of bacteria that is most known for spreading gastrointestinal diseases through food. These illnesses result in approximately 1.35 million infections, including over 25,000 hospitalizations each year, in the U.S. alone (CDC.gov). As antibiotic resistance becomes an increasingly urgent public health problem, the importance of developing alternative treatment methods is only becoming more crucial. One of the genes responsible for this virulence is known as hilA. HilA is the main transcriptional regulator of Salmonella Pathogenicity Island-1 gene (UniProt). SPI-1 plays an important role in the invasion of Salmonella into epithelial cells. The proteins encoded …

Implications Of Antibiotic And Bacteriophage Resistance In Environmentally Isolated E. Coli, Michael Connolly

Honors Theses

The increasing prevalence of antibiotic-resistant bacteria is an emerging problem for humans. Clinical misuse, overuse in agricultural and food settings, and limited numbers of new antibiotics have accelerated the proliferation of antibiotic-resistant bacteria. To confront this threat, scientists must develop new therapeutics that kill these antibiotic-resistant bacteria. In this study, we used Escherichia coli to analyze antibiotic and bacteriophage susceptibility. E. coli is a common, mostly benign, enteric, gram-negative bacteria. We isolated three E. coli strains from the Hans Groot Kill, a stream that runs through Union College’s campus. We sought to assess various E. coli strains’ antibiotic resistance, susceptibility …

The Role Of Fibroblast Growth Factor-9 In Influenza A Virus Pathogenesis, Bradley Edward Hiller

Arts & Sciences Electronic Theses and Dissertations

Influenza A virus (IAV) is a respiratory virus in the Orthomyxoviridae family which causes both seasonal epidemics and pandemics. IAV preferentially infects epithelial cells in the upper and lower respiratory tract, resulting in a range of disease severity from mild upper respiratory infections to potentially-lethal pneumonia. Ultimately, the severity of symptoms and complications from IAV infection depends on control of virus replication in the lungs, the inflammatory nature of the immune response, and the effectiveness of post-infection lung repair to regain pulmonary function. An arsenal of secreted proteins in the lung regulates these antiviral, inflammatory, and regenerative activities during infection, …

The Impact Of Processing Body Proteins On An Adenovirus Infection, La`Quita Randolph

Biology Theses

Adenovirus is a nonenveloped, double-stranded DNA virus that contains a 36 Kbp genome. The E4 ORF3 region of its genome consists of an E4 11k protein that can reorganize host cell components by relocalizing cellular proteins. One such cellular component is the cytoplasmic processing body, which consists of proteins involved in translational repression of mRNA and mRNA degradation. During an adenovirus infection, processing body proteins Ddx6 and Pat1b have been shown to colocalize and form aggresomes. Aggresomes induced by E4 11k are specific to the adenovirus serotype 5 (Ad 5). In this study, cytoplasmic Pat1b foci were observed and quantified …

Cat Covid, Cmv And Chemokines, Oh My!, Trevor Hancock

Doctoral Dissertations

Cytomegalovirus (CMV) is an important pathogen infecting most humans worldwide. CMV infection within immunocompromised individuals can cause severe morbidity and potential mortality. Disease during CMV infection is due to virus dissemination and subsequent inflammation. Host immune cells lie at the intersection potentially mediating both. The CMV-encoded viral chemokine vCXCL-1 is a proposed virulence factor in mouse models increasing immune cell recruitment and disease. However, the primary immune cell mediator is undetermined. To identify targets, Chapter 2 examines CXCR2 expression (receptor for vCXCL-1) among various mouse tissues and human peripheral blood under steady-state conditions. In vitro, isoforms of HCMV’s vCXCL-1 …

Novel Ultraviolet Light Technologies For The Inactivation Of Murine Hepatitis Virus, A Sars-Cov-2 Surrogate, Alexia E. Angelos, Doris H. D'Souza

Chancellor’s Honors Program Projects

No abstract provided.

Mathematical Modeling Suggests Cooperation Of Plant-Infecting Viruses, Joshua Miller, Vitaly V. Ganusov, Tessa Burch-Smith

Chancellor’s Honors Program Projects

No abstract provided.

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 …

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 …

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.

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 …

An Investigation Of Hhv6'S Impact On The Cognitive Progression And Microglial Changes In An Alzheimer's Disease Cohort, Charles E. Seaks

Theses and Dissertations--Physiology

The role of herpesviruses and, more specifically, HHV6 in the development of Alzheimer’s disease (AD) and associated cognitive decline is still being investigated. High ubiquity and prevalence in the population have led to a high degree of skepticism about HHV6 as a potential contributor to cognitive decline and dementias. However, recent evidence related to another herpesvirus, herpes simplex virus 1, suggests that reactivation, not carriage, of the virus may be the key factor to explain the dissonance between the virus’ ubiquity and contributions to dementias. With that in mind, we set out to assess cases from the Sanders-Brown Center on …

Development Of Novel Vaccination Strategies Against Emerging Bunyaviruses, Tomaz Manzoni

Publicly Accessible Penn Dissertations

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a highly pathogenic emergent bunyavirus. First isolated in 2009 in China, SFTSV is now endemic to several east Asian countries where high case fatality ratios of 6-30% are reported. The primary tick vector of SFTSV, Haemaphysalis longicornis, has a large range and is a well reported invasive species throughout the world. This, in addition to SFTSV’s ability to spread in the absence of its vector in nosocomial and veterinary settings, suggests SFTSV is well suited to cause widespread lethal outbreaks. Currently no vaccines or therapeutics against SFTSV exist, prompting health agencies to …

Response And Molecular Control Of Cd8 T Cells During Infection And Cancer, Nicholas K. Preiss Dr.

Dartmouth College Ph.D Dissertations

CD8 T cells are potent immune effector cells capable of vast clonal expansion and clearance of infected or cancerous cells. After control of the pathogenic insult, CD8 T cells develop into quiescent, long-lived memory populations that are poised to mediate rapid protection upon reencounter with cognate antigen. These properties make control of CD8 T cell responses a highly desirable outcome of vaccine strategies and immunotherapy. Therefore, understanding how the effector function and memory differentiation of CD8 T cells are controlled at a molecular level is of great importance. In the context of infection with gammaherpesviruses (γHV), which form a latent …