Virology Commons^™

Intrinsic And Extrinsic Drivers Of Bioaerosol Decay: Investigating Pathogen Stability Of Bacteriophage Ms2, Sin Nombre Virus, And Sars-Cov-2 In Simulated Environments, Elizabeth A. Klug

Theses & Dissertations

The threat posed by a virus as a bioaerosol depends largely on its stability under various environmental conditions (relative humidity (RH), sunlight, ozone, etc.). This stability is typically studied through aerosol decay—how the virus' viability changes over time when exposed environmental conditions. The Goldberg rotating drum, a widely used tool for studying bioaerosols, has been the basis of such research (Goldberg et al., 1958). However, it has significant limitations, including an inability to measure initial pathogen infectivity loss and the use of small sample volumes. Additionally, it does not answer the question of what intrinsic factors (lipids, proteins, nucleic acids) …

Understanding The Effect Of Chikungunya Virus Infection On Bone Homeostasis, Enakshi Roy

Theses & Dissertations

Chikungunya virus (CHIKV) is a mosquito-borne virus that causes Chikungunya fever (CHIKF), characterized by high fever, headache, rash, and joint pain. With global travel on the rise, infections caused by CHIKV have emerged in new regions, expanding their geographic range and infecting susceptible hosts. Currently, no approved prophylactic or therapeutic measures exist to prevent or treat these infections, with prevention strategies primarily focused on vector control. However, these measures have proven inadequate due to the emergence of mutations that enhance viral transmission or vector range. Therefore, urgent attention is needed to develop therapies to treat the infection. Although CHIKV has …

Crispr Technology As An Antiviral In Dsdna And Ssrna Viruses, Cathryn Mayes

Theses & Dissertations

The COVID-19 pandemic highlights the necessity of emergency response and pandemic preparedness, especially for emerging viral threats. Currently, virus-specific vaccines and antivirals are the primary tools to combat viral diseases; however, broad-spectrum antivirals that target more than one virus species could provide additional protection from emerging and re-emerging viral diseases (Andersen et al. 2020; Zhu et al. 2015; Hickman et al. 2022).

Clustered regulatory interspaced short palindromic repeat (CRISPR)-associated endonucleases have become recently utilized as potential antiviral strategies due to their high specificity, efficacy, and versatility (Najafi et al. 2022). While CRISPR-based antivirals have previously been used to target specific …

Investigating The Role Of Sphingosine Kinases During Alphavirus Infection, Opeoluwa Oyewole

Theses & Dissertations

Several alphaviruses, critical human pathogens, have re-emerged in recent years. Alphaviruses are found on all continents and infect both invertebrates and vertebrates, including some aquatic animals. They are classified as arboviruses because hematophagous arthropods transmit them. Based on the symptoms they cause, alphaviruses are classified as either arthritogenic or encephalitic.

Rising global travel has led to outbreaks of infections in new regions, increasing the geographical ranges of alphaviruses and causing new infections in susceptible hosts. Currently, there are no approved prophylactic or therapeutic measures to prevent or treat alphavirus infections; prevention measures have focused on vector control. These measures are …

Gut Commensals Modulate Siv/Shiv Pathogenesis And Therapeutics, Samuel Johnson

Theses & Dissertations

Despite significant advancements in combination antiretroviral therapy (cART), ongoing inflammation in the brain and gut remain two of the most significant hurdles in the health of people living with human immunodeficiency virus (HIV). Additionally, a viral reservoir in each compartment inhibits cure efforts by allowing rapid viral rebound following cART interruption. Emerging understanding of the gut-brain axis (GBA) implicates each compartment in the modulation of the other in a complex bi-directional interaction mediated by vagus innervation, circulating lymphocytes, and microbiome composition and biproducts. Using multiple models of the simian (and simian-human) immunodeficiency virus (SIV/SHIV) and therapeutic intervention, I present how …

Role Of Endocytic Machinery Regulators In Egfr Traffic And Viral Entry, Insha Mushtaq

Theses & Dissertations

STUDY 1: Role of endocytic regulator EHD1 and its binding partner RUSC2 in EGFR traffic

Abstract

Epidermal growth factor receptor (EGFR) is a prototype receptor tyrosine kinase and an oncoprotein in many solid tumors. Cell surface display of EGFR is essential for cellular responses to its ligands. While post activation endocytic trafficking of EGFR has been well elucidated, little is known about mechanisms of basal/pre-activation surface display of EGFR. Here, we identify a novel role of the endocytic regulator EHD1 and a potential EHD1 partner, RUSC2, in cell surface display of EGFR. EHD1 and RUSC2 colocalize with EGFR in vesicular/tubular …

Multistrain Hiv-1 Elimination: A Crispr-Cas9 And Theranostics-Based Approach, Jonathan Herskovitz

Theses & Dissertations

A critical barrier to achieving a functional cure for infection by human immunodeficiency virus type one (HIV-1) rests in the presence of latent proviral DNA integrated in the nuclei of host CD4+ T cells and mononuclear phagocytes. Accordingly, HIV-1-infected patients must adhere to lifelong regimens of antiretroviral therapy (ART) to prevent viral rebound, CD4+ T cell decline, and progression to acquired immunodeficiency syndrome (AIDS). Gene editing using clustered regularly interspersed short palindromic repeat (CRISPR)-Cas9 technology stands as one means to inactivate integrated proviral DNA. We devised a mosaic gRNA CRISPR-Cas9 system- TatDE- that targets viral transcriptional regulator genes tat / …

Synthesis And Characterization Of A Long-Acting Emtricitabine Prodrug Nanoformulation, Ibrahim M. Ibrahim

Theses & Dissertations

The introduction of highly active antiretroviral therapy led to a paradigm shift in the management of HIV/AIDS changing a disease considered “a death sentence” to “a manageable chronic disease”. Nevertheless, challenges exist for successful treatment of HIV, including patient adherence to the complex daily regimens and the inability of current formulations to target viral sanctuaries. Introduction of nanoformulated antiretroviral therapy (ART) is a promising alternative to tackle these challenges. Our laboratory has been focusing on developing long-acting (LA) nanoformulated antiretrovirals and has succeeded in developing LA integrase inhibitors. However, challenges for this approach extend to a range of short-acting hydrophilic …

Development Of A Long-Acting Nanoformulation Of Dolutegravir For Prevention And Treatment Of Hiv-1 Infection, Brady Sillman

Theses & Dissertations

Dolutegravir (DTG) is a potent human immunodeficiency virus type 1 (HIV-1) integrase strand-transfer inhibitor (INSTI) with a high barrier to viral drug resistance. However, opportunities to improve its profile abound. These include extending the drug’s apparent half-life, increasing penetrance to “putative” viral reservoirs, and reducing inherent toxicities. These highlight, in part, the need for long-acting, slow effective release antiretroviral therapy (LASER ART) delivery schemes. A long-acting (LA) DTG was made by synthesizing a hydrophobic and lipophilic prodrug encased with poloxamer (P407) surfactant. This modified DTG (MDTG) reduced systemic metabolism and polarity, increased lipophilicity and membrane permeability, improved encapsulation, and formed …

Role Of Stemloop D In Terminally Deleted Coxsackievirus B3 Replication, Lee K. Jaramillo

Theses & Dissertations

Coxsackievirus B3 (CVB3) is an enterovirus with no known form of latency. However, assays designed to detect enteroviral RNA have shown that CVB3 RNA can persist for weeks beyond the acute infection both naturally and experimentally. Our previous work with coxsackievirus revealed an inhibited version of enteroviral replication where the progeny virus, termed terminally deleted (TD) virus, was missing a maximum of 49 nucleotides from the beginning of the 5’ non-translated region (NTR). The largest terminally deleted virus, TD50, effaced stem a, stemloop b, and stemloop c from the secondary structure, the cloverleaf. We hypothesized that further deletion beyond those …

Characterization Of The Replication Of Coxsackievirus B3 With A Mutationally Disrupted Cre(2c) And The Use Of Creatinine-Hydrochloride As An Antibacterial Agent, Shane E. Smithee

Theses & Dissertations

Following natural or experimental infection, and in cell culture, coxsackie B virus (CVB) RNA can persist for weeks in the absence of CPE yet with detectable viral RNA. Earlier studies in our laboratory demonstrated that this persistence produced viral RNA with up to 49 nucleotide deletions at the 5’ genomic terminus, partially degrading the cloverleaf (or domain I), an RNA structure that is required for efficient viral replication. A cis-acting replication element (CRE) in the 2C protein coding region [CRE(2C)] templates the addition of two uridine residues to the virus-encoded RNA replication primer, VPg, prior to genomic replication. Because …