Virology Commons^™

The Shape Of U: Mapping Out Protective Elements In Mrna Escapees, Jacob Miles

Masters Theses

A crucial step of the viral life cycle of Kaposi’s Sarcoma Herpesvirus (KSHV) lytic infection is the triggering of a massive RNA decay event termed “Host Shutoff”. Host Shutoff is driven by the viral endonuclease SOX which leads to the destruction of over 70% of the total transcriptome. This process cripples cellular gene expression and allows for viral reprograming of the cell for the purpose of viral replication. Co-evolution has led to the host developing a multitude of antiviral defenses aimed at preserving certain cellular RNAs linked to antiviral responses. One such defense are RNA secondary structures located within the …

Applied Molecular Dynamics: From Targeting Viral Helicases, To Understanding The Interactions Of Cucurbituril Complexes In Ionic Solutions, Bryan Raubenolt

University of New Orleans Theses and Dissertations

Molecular Dynamics simulations are a highly useful tool in helping understand the fundamental interactions present in a variety of chemical systems. The work discussed here illustrates it’s use in determining the conformational dynamics of the Zika and SARS-Cov-2 helicase in a physiological environment, largely in an effort to discover inhibitors capable of rendering the protein inert. Additionally, we show how it can be used to understand paradoxical trends in the anion-induced precipitation of Cucurbituril cavitands.

Viral helicases are motor proteins tasked with unwinding the viral dsRNA, a crucial step in preparing the strand to be translatable by host cells. By …

Structural Insights Into Host-Pathogen Interactions Of Alphaviruses, Katherine Basore

Arts & Sciences Electronic Theses and Dissertations

Alphaviruses are arthropod-borne, single-stranded positive-sense RNA viruses of the Togaviridae family that infect various vertebrates worldwide in tropical and temperate areas, causing emerging and reemerging diseases in humans. Mature virions are 70 nm in diameter and contain a ~11-kilobase genome encapsidated within a nucleocapsid core, a host-derived lipid bilayer, and an envelope comprised of heterodimers of the glycoproteins E1 and E2 arranged into trimeric spikes with T=4 icosahedral symmetry. Alphaviruses are categorized into two groups based on their clinical symptoms: the arthritogenic alphaviruses, such as chikungunya (CHIKV), Mayaro (MAYV), Ross River (RRV), Semliki Forest (SFV), and O’nyong-nyong (ONNV) viruses, which …

Structural Characterization Of Two Large Icosahedral Dna Viruses And Their Capsid Assembly Mechanisms, Yuejiao Xian

Open Access Theses & Dissertations

In the last three decades, many large DNA viruses were discovered and grouped into a loosely defined clade of Nucleocytoplasmic Large DNA Viruses (NCLDVs). NCLDVs infect a wide range of hosts from single cellular protists to large animals. Recently, these viruses were classified as a new phylum of Nucleocytoviricota under the kingdom of Bamfordvirae. The genomes of these Nucleocytoviricota viruses (NCVs) are remarkedly large and complicated, containing many cellular genes from all three domains of life, which raised intensive debates on their evolutionary origins. Despite being classified in the same phylum, their physical structures vary and can be roughly classified …

Molecular Identification And Characterization Of Viral Pathogens Infecting Sweet Cherry, Aaron J. Simkovich

Electronic Thesis and Dissertation Repository

Stone fruits are a valuable crop grown worldwide, however pathogens such as viruses threaten fruit production by reducing tree health and fruit yield. In an orchard within the Niagara region of Ontario, symptoms typical of viral infection such as chlorosis and leaf deformation were seen on sweet cherry (Prunus avium L.) trees. Next generation sequencing was performed on symptomatic and asymptomatic leaves and four viruses were identified. On the tree displaying the most severe symptoms, Prune dwarf virus (PDV), was the only virus detected. A survey conducted during this work showed 42% of cherry trees on a single …

Small Molecule Synthetic Carbohydrate Receptors, Marcelo F. Bravo Carranco

Dissertations, Theses, and Capstone Projects

Carbohydrate – receptor interactions are often involved in the attachment of viruses to host cells, and this docking is a necessary step in the virus life cycle that precedes infection and, ultimately, replication. Despite the conserved structures of the glycans involved in docking, they are still considered “undruggable”, meaning these glycans are beyond the scope of conventional pharmacological strategies. Recent advances in the development of synthetic carbohydrate receptors (SCRs) – small molecules that bind carbohydrates – could bring carbohydrate-receptor interactions within the purview of druggable targets. Here we discuss the role of carbohydrate-receptor interactions in viral infection, the evolution of …

Quantification Of Interactions Between Influenza Hemagglutinin And Host Cell Phosphoinositides By Super-Resolution Microscopy, Matthew T. Parent

Electronic Theses and Dissertations

The influenza viral membrane protein hemagglutinin (HA) forms dense nanoscale clusters on host cell plasma membranes (PM), but the mechanisms that direct HA clustering are not well understood. Previous studies have observed HA associated with actin rich regions of the PM, but there are no known direct interactions between HA and actin. Phosphatidylinositol 4,5-biphosphate (PIP2) is a signaling lipid in the PM which can regulate the actin cytoskeleton, and actin comets initiated by PIP2 are known to be exploited by HA to reach the PM of infected cells. PIP2 is also used by other viruses, such as HIV and Ebola, …

A Review Of Human Immunodeficiency Virus, Sophie Silver

Senior Honors Theses

Human immunodeficiency virus, also referred to as HIV, is a devastating virus which has infected millions. Characterized as a retrovirus, HIV has an RNA genome, which is reverse transcribed into DNA upon entry into the host cell. HIV primarily affects CD4⁺ T cells and is diagnosed by the significant reduction of CD4⁺ T cells. While no cure has been discovered yet, antiretroviral therapy (ART) has been demonstrated as an effective treatment option. In the progression of HIV, additional HIV-associated diseases may arise, including HIV-associated psoriasis and sensory neuropathy. In addition to the use of ART, clinicians often prescribe …

Functional Sites Within The Ihnv Nonvirion Protein That Regulate Host Cellular Responses, Jeff Ringiesn, Bartolomeo Gorgoglione, Douglas W. Leaman

Symposium of Student Research, Scholarship, and Creative Activities Materials

Fish Rhabdoviruses are responsible for causing fatal epizootics within commercial and wild populations of various fish species around the world. Infectious hematopoietic necrosis virus (IHNV), also known as the Salmonid novirhabdovirus, is enzootic along the Pacific Coast of North America and is comprised of five genogroups, each of which is endemic to a specific geographical location. Once the virus enters the host through the fin epithelia, IHNV infection causes infectious hematopoietic necrosis in salmonid species. The disease is highly fatal and presents with signs such as abdominal distension, bulging of the eyes, anemia, and necrosis of vital organs such as …

Pneumovirus Infections: Understanding Rsv And Hmpv Entry, Replication, And Spread, Jonathan T. Kinder

Theses and Dissertations--Molecular and Cellular Biochemistry

Pneumoviruses including human metapneumovirus (HMPV) and respiratory syncytial virus (RSV) are significant causes of respiratory tract infections globally. Children, elderly, and immunocompromised patients are at the greatest risk for developing severe infections, which can have devastating outcomes. Although these viruses are ubiquitous with significant impacts on human health, there are no antivirals or vaccines available. The only FDA approved therapy is a monoclonal antibody for RSV, given prophylactically during the infectious season, and this treatment is only available for high risk infants. The work presented in this thesis aims to increase our understanding of how these viruses enter, replicate, and …

Regulation Of Gene Expression Through Ribosome-Associated Proteins, Clare Margaret Miller

Legacy Theses & Dissertations (2009 - 2024)

Translation is a crucial mechanism for generating proteins to carry out cellular processes and for ensuring proper cell functions. Ribosomes are at the center of translation and are complex pieces of machinery. They consist of at least 80 core eukaryotic ribosomal proteins, which are conserved from prokaryotes, and four ribosomal RNAs (rRNAs): 18S, 28S, 5,8A 5S. In addition, numerous translation factors aid the ribosome in protein production. While ribosomes are typically described by these core features, they are known to exist in a heterogenous pool with variations in protein composition, modifications of rRNA, and an assortment of non-ribosomal proteins that …

Characterization Of The Influences Of Human Cytomegalovirus Glycoprotein O (Go) Expression On Gh/Gl Complexes Assembly And Its Polymorphisms On Cell-Free And Cell-To-Cell Spread, And Antibody Neutralization., Le Z. Day

Graduate Student Theses, Dissertations, & Professional Papers

Human cytomegalovirus (HCMV) is widely spread throughout the world and immunocompromised individuals can suffer severe diseases from HCMV infection. Once the infection is established, HCMV can spread through the body and infect many major somatic cell types. The glycoproteins H and L (gH/gL) on HCMV envelope can be bound by either gO or the UL128-131 proteins to form complexes gH/gL/gO and gH/gL/UL128-131 that are critical for viral entry and spread, and these two complexes are important targets of neutralizing antibodies. Strains of HCMV vary considerably in the levels of gH/gL/gO and gH/gL/UL128-131. gO is one of the most diverse loci …