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Articles 31 - 60 of 120

Full-Text Articles in Virology

Viruses In Astrobiology, Ignacio De La Higuera, Ester Lázaro Oct 2022

Viruses In Astrobiology, Ignacio De La Higuera, Ester Lázaro

Biology Faculty Publications and Presentations

Viruses are the most abundant biological entities on Earth, and yet, they have not received enough consideration in astrobiology. Viruses are also extraordinarily diverse, which is evident in the types of relationships they establish with their host, their strategies to store and replicate their genetic information and the enormous diversity of genes they contain. A viral population, especially if it corresponds to a virus with an RNA genome, can contain an array of sequence variants that greatly exceeds what is present in most cell populations. The fact that viruses always need cellular resources to multiply means that they establish very …


Bird Species Define The Relationship Between West Nile Viremia And Infectiousness To Culex Pipiens Mosquitoes, Jefferson A. Vaughan, Robert Newman, Michael J. Turrell Oct 2022

Bird Species Define The Relationship Between West Nile Viremia And Infectiousness To Culex Pipiens Mosquitoes, Jefferson A. Vaughan, Robert Newman, Michael J. Turrell

Biology Faculty Publications

The transmission cycle of West Nile virus (WNV) involves multiple species of birds. The relative importance of various bird species to the overall transmission is often inferred from the level and duration of viremia that they experience upon infection. Reports utilizing in vitro feeding techniques suggest that the source and condition of blood in which arboviruses are fed to mosquitoes can significantly alter the infectiousness of arbovirus to mosquitoes. We confirmed this using live hosts. A series of mosquito feedings with Culex pipiens was conducted on WNV-infected American robins and common grackles over a range of viremias. Mosquitoes were assayed …


Forty Years Without Family: Three Novel Bacteriophages With High Similarity To Spp1 Reveal Decades Of Evolutionary Stasis Since The Isolation Of Their Famous Relative, Veronique A. Delesalle, Brianne E. Tomko, Albert C. Vill, Katherine B. Lichty, Gregory P. Krukonis Sep 2022

Forty Years Without Family: Three Novel Bacteriophages With High Similarity To Spp1 Reveal Decades Of Evolutionary Stasis Since The Isolation Of Their Famous Relative, Veronique A. Delesalle, Brianne E. Tomko, Albert C. Vill, Katherine B. Lichty, Gregory P. Krukonis

Biology Faculty Publications

SPP1, an extensively studied bacteriophage of the Gram-positive Bacillus subtilis, is a model system for the study of phage–host interactions. Despite progress in the isolation and characterization of Bacillus phages, no previously fully sequenced phages have shared more than passing genetic similarity to SPP1. Here, we describe three virulent phages very similar to SPP1; SPP1 has greater than 80% nucleotide sequence identity and shares more that 85% of its protein coding genes with these phages. This is remarkable, given more than 40 years between the isolation of SPP1 and these phages. All three phages have somewhat larger genomes and more …


Mathematical Modeling Of Potassium Modulated Viral Infection, Zaira Elizabeth Mather May 2022

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 …


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 Jan 2022

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 …


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 Jan 2022

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 …


The Isolation And Characterization Of Bacteriophage Hasitha, Gillian Brown Jan 2022

The Isolation And Characterization Of Bacteriophage Hasitha, Gillian Brown

Mahurin Honors College Capstone Experience/Thesis Projects

Microbacteriophage Hasitha is a virus that infects Microbacterium foliorum, a bacterium associated with grasses that was first discovered in Germany. Hasitha was isolated from an enriched compost sample and is of particular interest due to its unusual growth pattern. Most bacteriophages require actively growing host cells to produce new phage progeny. However, Hasitha can infect and kill stationary (non-replicating) bacterial cells. We discovered this unusual characteristic through a fortuitous observation of infected lawns that were allowed to incubate in the lab workspace for approximately one month. During this time, a noticeable “halo” grew around the initial site of infection …


Isolation And Characterization Of Novel B. Subtilis Bacteriophages, Johnson Phung, Rebecca Adams Jan 2022

Isolation And Characterization Of Novel B. Subtilis Bacteriophages, Johnson Phung, Rebecca Adams

Science University Research Symposium (SURS)

Bacteriophages are viruses that infect bacteria cells. Bacteria, being the most abundant form of life on the planet, have an estimated ten to a hundred different types of bacteriophages that infect each species. Bacteriophages are everywhere on Earth, but the number of phages that have been identified is only a fraction of what are thought to exist. This project focuses on isolating and identifying phages that infect the bacterium Bacillus subtilis. B subtilis is a decomposition microbe commonly found in the soil. Our first goal was to determine whether the 3 samples of Bacillus subtilis phages that were previously …


Virology: Mutagenizing The Proteolytic Cleavage Site In The Major Capsid Protein In Ssv1, Thejanee Liyanaarachchi Dec 2021

Virology: Mutagenizing The Proteolytic Cleavage Site In The Major Capsid Protein In Ssv1, Thejanee Liyanaarachchi

University Honors Theses

SSV1, spindle-shaped virus 1, is an archaeal virus with a unique shape that belongs to the family of fuselloviruses and infects hyperthermophilic archaea that thrive at 80°C and pH 3. SSV1 has two capsid proteins, VP1 and VP3, that presumably produce the lemon-shaped virion structure characteristic of fuselloviruses. The VP1 amino acid sequence is highly conserved among SSVs. Here, we investigate the importance of the proteolytic cleavage site in position E66 in VP1 by changing its glutamic acid to the other 19 amino acids. We have developed a new protocol for creating SSV1 mutants through HiFi Assembly (NEB) to increase …


A Bioinformatic And Biochemical Analysis Of Cruciviruses, George William Kasun Oct 2021

A Bioinformatic And Biochemical Analysis Of Cruciviruses, George William Kasun

Dissertations and Theses

Cruciviruses are novel ssDNA viruses discovered through metagenomics and direct environmental DNA amplification and cloning. The genomes of cruciviruses suggest that gene transfer between RNA and DNA viruses occurred due to the presence of putative protein-encoding genes that are homologous to both ssRNA and ssDNA viruses. In order to gain a better understanding of this group of viruses both bioinformatic analyses and in vitro biochemical experiments were employed. The results of the bioinformatic analyses show that cruciviruses are a highly diverse group of ssDNA viruses. Their placement within established ssDNA phylogenies is difficult due to heterogeneity in their putative replication-associated …


Bacteriophages Infecting Enterobacter Cloacae To Reduce Bloater Damage In Fermented Cucumbers Aug 2021

Bacteriophages Infecting Enterobacter Cloacae To Reduce Bloater Damage In Fermented Cucumbers

Symposium of Student Scholars

Fermented cucumbers are one of the most important fermented vegetables consumed worldwide. During cucumber fermentations, certain undesirable changes may occur. One of such changes is known as bloater defect (hollow cavities in fermented cucumbers), which is primarily caused by gas-producing bacteria including Enterobacter cloacae. Bloater defect lowers product quality and leads to significant economic loss to the pickle industry, and effective preventative methods are needed. Bacteriophages (phages) are highly host-specific bacterial killers. Use of phages to control unwanted bacteria in foods is a promising approach because phages do not change food properties. This research was to isolate, characterize, and …


Ruvb-Like Protein 2 Interacts With The Ns1 Protein Of Influenza A Virus And Affects Apoptosis That Is Counterbalanced By Type I Interferons, Yimeng Wang, Jianhong Zhou, Samuel G. Mackintosh, Yuchun Du Jun 2021

Ruvb-Like Protein 2 Interacts With The Ns1 Protein Of Influenza A Virus And Affects Apoptosis That Is Counterbalanced By Type I Interferons, Yimeng Wang, Jianhong Zhou, Samuel G. Mackintosh, Yuchun Du

Biological Sciences Faculty Publications and Presentations

The NS1 protein of influenza A virus (IAV) plays important roles in viral pathogenesis and host immune response. Through a proteomic approach, we have identified RuvB-like proteins 1 and 2 (RuvBL1 and RuvBL2) as interacting partners of the NS1 protein of IAVs. Infection of human lung A549 cells with A/PR/8/34 (PR8) virus resulted in reductions in the protein levels of RuvBL2 but not RuvBL1. Further studies with RuvBL2 demonstrated that the NS1-RuvBL2 interaction is RNA-independent, and RuvBL2 binds the RNA-binding domain of the NS1. Infection of interferon (IFN)-deficient Vero cells with wild-type or delNS1 PR8 virus reduced RuvBL2 protein levels …


Characterization Of Novel Chlorovirus Glycosyltransferases That Synthesize Atypical Glycans, Eric Noel Apr 2021

Characterization Of Novel Chlorovirus Glycosyltransferases That Synthesize Atypical Glycans, Eric Noel

School of Biological Sciences: Dissertations, Theses, and Student Research

Giant dsDNA chloroviruses encode a diverse repertoire of glycosyltransferases (GTases) and methyltransferases (MTases) that biosynthesize unusual, methylated sugars independent of their host chlorella-like green algae prompting a reexamination of glycobiology systems. Unlike most other viruses, the prototype chlorovirus PBCV-1 encodes most, if not all, of the machinery required to glycosylate its major capsid protein (MCP). The structures of the four N-linked glycans do not resemble any other glycans in the three domains of life. Here, we investigated the potential involvement of chlorovirus- encoded putative GTases and MTases in glycosylation of the viral MCP. First, we aimed to generate site-directed …


Disruption Of Cellular P-Bodies During An Adenovirus Infection​, La`Quita Randolph, Kevin Neubrecht, Kasey A. Karen Jan 2021

Disruption Of Cellular P-Bodies During An Adenovirus Infection​, La`Quita Randolph, Kevin Neubrecht, Kasey A. Karen

Graduate Research Showcase

Adenovirus has made major contributions in medicine by serving as a model DNA virus to study other viruses, such as human papillomavirus (HPV). Adenoviruses are a diverse family of nonenveloped, double-stranded DNA viruses that are ubiquitous to animals and humans. There are over 67 serotypes of human adenoviruses that can cause a variety of illnesses including, gastroenteritis, conjunctivitis and respiratory infections. Adenovirus can cause these infections by invading host cells and producing an environment that is favorable for viral replication. During the early phases of infection, adenovirus expresses various viral proteins such as E4 11k, which has multiple functions. One …


Optimized Microbial Recombinant Production Of Hiv-1 Anti-Envelope Antibody Fragments With Applications To Single Particle Tracking Of Virus Assembly, Merissa Michelle Bruns Jan 2021

Optimized Microbial Recombinant Production Of Hiv-1 Anti-Envelope Antibody Fragments With Applications To Single Particle Tracking Of Virus Assembly, Merissa Michelle Bruns

Electronic Theses and Dissertations

In my findings, I have established a set series of protocols to recombinantly produce, purify and apply various fluorescent probes in vitro for the fluorescent labeling and study of the human immunodeficiency virus type 1 (HIV-1) envelope (Env) protein during HIV viral assembly. There remains insufficient knowledge about the molecular dynamics and interactions of HIV-1 Env protein with its counterpart, Gag, on the inner host cell surface during assembly of a mature virus particle. There also remains an insufficient amount of data for the understanding and clarification of the mechanism of action of a known host cell HIV-1 restriction factor, …


The Role Of Conserved Poly(A) Sequences In The 3'Utr Of Zika Virus Gene Expression, Kristen Kaytes Jan 2021

The Role Of Conserved Poly(A) Sequences In The 3'Utr Of Zika Virus Gene Expression, Kristen Kaytes

Legacy Theses & Dissertations (2009 - 2024)

Following its discovery in 1947, Zika virus garnered little attention in the global stage until 2015, when a rapidly spreading epidemic brought the virus, and its devastating clinical manifestations to light. Zika virus pathologies include Congenital Zika Syndrome, a known causative of microcephaly, as well as spontaneous miscarriages and the development of Guillain Barré syndrome. Despite recent advances in research, the molecular biology of Zika virus is largely unknown.


Ngs Rna-Seq Reveals Bromovirus Encapsidate Native And Recombinant Viral Rnas, As Well As Cellular Rnas From The Host, Nipin Shrestha Jan 2021

Ngs Rna-Seq Reveals Bromovirus Encapsidate Native And Recombinant Viral Rnas, As Well As Cellular Rnas From The Host, Nipin Shrestha

Graduate Research Theses & Dissertations

Brome mosaic virus (BMV), Cowpea chlorotic mottle virus (CCMV), and Broad bean mottle virus (BBMV), the members of the genus Bromovirus, are the experimental model viruses in this dissertation research. Packaging of the RNA genome by the viruses is known to be highly selective and specific for the viral RNA but, not 100% accurate. There is evidence that the viruses specifically or accidentally encapsidate viral RNA variants and host (cellular) RNAs. The scope of this dissertation is to identify different types of RNAs that can be packaged by viruses along with the viral RNAs of parental origin.BMV, CCMV, and BBMV …


Polerovirus Genomic Variation And Mechanisms Of Silencing Suppression By P0 Protein, Natalie Holste Nov 2020

Polerovirus Genomic Variation And Mechanisms Of Silencing Suppression By P0 Protein, Natalie Holste

School of Biological Sciences: Dissertations, Theses, and Student Research

The family Luteoviridae consists of three genera: Luteovirus, Enamovirus, and Polerovirus. The genus Polerovirus contains 32 virus species. All are transmitted by aphids and can infect a wide variety of crops from cereals and wheat to cucurbits and peppers. However, little is known about how this wide range of hosts and vectors developed. In poleroviruses, aphid transmission and virion formation is mediated by the coat protein read-through domain (CPRT) while silencing suppression and phloem limitation is mediated by Protein 0 (P0)—a protein unique to poleroviruses. P0 gives poleroviruses a great advantage amongst plant viruses and diversifies polerovirus species, but the …


Endothelial Cell Contributions To Covid-19, Alexandra E. Oxford, Fabio Halla, Evan B. Robertson, Brad E. Morrison Oct 2020

Endothelial Cell Contributions To Covid-19, Alexandra E. Oxford, Fabio Halla, Evan B. Robertson, Brad E. Morrison

Biology Faculty Publications and Presentations

Understanding of the clinical, histological and molecular features of the novel coronavirus 2019 (Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)) has remained elusive. Coronavirus disease 2019 (COVID-19) caused by this virus has unusual clinical presentation with regard to other related coronaviruses. Recent reports suggest that SARS-CoV-2, unlike other related viruses, infects and replicates within endothelial cells, which may explain a significant portion of the observed clinical pathology. Likewise, mounting evidence associates vascular and endothelial cell dysfunction with increased mortality. This review focuses on understanding how endothelial cell pathology is caused by SARS-CoV-2 at the molecular and cellular levels and how …


Covid-19: In The Absence Of Vaccination – ‘Mask-The-Nation’, Roy D. Sleator, Steven Darby, Alan Giltinan, Niall Smith Jul 2020

Covid-19: In The Absence Of Vaccination – ‘Mask-The-Nation’, Roy D. Sleator, Steven Darby, Alan Giltinan, Niall Smith

Department of Biological Sciences Publications

“In the absence of a vaccine, or effective antiviral, one of our only remaining strategies for controlling COVID-19 is to physically block the spread of SARS-CoV-2 in the community”


Host-Dependent Differences In Replication Strategy Of The Sulfolobus Spindle-Shaped Virus Strain Ssv9 (A.K.A., Ssvk1): Infection Profiles In Hosts Of The Family Sulfolobaceae, Ruben M. Ceballos, Coyne Gareth Drummond, Carson Len Stacy, Elizabeth Padillo-Crespo, Kenneth M. Stedman Jul 2020

Host-Dependent Differences In Replication Strategy Of The Sulfolobus Spindle-Shaped Virus Strain Ssv9 (A.K.A., Ssvk1): Infection Profiles In Hosts Of The Family Sulfolobaceae, Ruben M. Ceballos, Coyne Gareth Drummond, Carson Len Stacy, Elizabeth Padillo-Crespo, Kenneth M. Stedman

Biology Faculty Publications and Presentations

The Sulfolobus Spindle-shaped Virus (SSV) system has become a model for studying thermophilic virus biology, including archaeal host-virus interactions and biogeography. Several factors make the SSV system amenable to studying archaeal genetic mechanisms (e.g., CRISPRs) as well as virus-host interactions in high temperature acidic environments. Previously, we reported that SSVs exhibited differential infectivity on allopatric vs. sympatric hosts. We also noticed a wide host range for virus strain SSV9 (a.k.a., SSVK1). For decades, SSVs have been described as “non-lytic” double-stranded DNA viruses that infect species of the genus Sulfolobus and release virions via budding rather than host lysis. In this …


Lysogeny And Use Of Mycobacteriophage Pita2, Eleanor Behling, Neocles B. Leontis, Jill Zeilstra-Ryalls May 2020

Lysogeny And Use Of Mycobacteriophage Pita2, Eleanor Behling, Neocles B. Leontis, Jill Zeilstra-Ryalls

Honors Projects

The CDC has classified antibiotic resistance as the biggest health challenge of our era; every year 2 million lives are impacted and even lost due to resistant bacteria. Bacteriophages provide an alternative route to fighting infections that does not further the development of antibiotic resistance among bacterial species. A bacteriophage replicates inside a bacterial cell and then causes that cell to lyse, an event that kills the bacterial host. However, some phage can integrate their genomes into the host chromosome without causing lysis. The HHMI SEA-PHAGES program has generated a collection of bacteriophage that infect Actinobacteria species. Over 13,000 phages …


Comment: Probably A Good News: Covid-19 Is Not Spreading Fast In Tropical Region Like In Temperate Region, Madeeha Manzoor Apr 2020

Comment: Probably A Good News: Covid-19 Is Not Spreading Fast In Tropical Region Like In Temperate Region, Madeeha Manzoor

Journal of Bioresource Management

My understanding of Covid-19 is that, there are some climatic factors involved in seed spread of this virus. As it started from the area of China which falls under temperate zone, its second victim was Iran’s city Qom which also falls under temperate zone and third is Italy which is completely in temperate zone.

Data from two countries from Temperate zone and three countries from Tropical zone was compared. The days counted from the 100 cases each country reached as day one and further days studied on equal basis.


Mechanisms Of Silencing Suppression By A Polerovirus P0 Protein, Natalie Holste, Hernan Garcia-Ruiz Apr 2020

Mechanisms Of Silencing Suppression By A Polerovirus P0 Protein, Natalie Holste, Hernan Garcia-Ruiz

School of Biological Sciences: Presentations

Maize lethal necrosis is an intense viral disease spreading across sub-Saharan Africa. Maize is the staple crop grown in sub-Saharan Africa, but most crops infected with maize lethal necrosis will not survive to harvest. This causes immense economic hardship and starvation within the population. Maize lethal necrosis consists of a combination of two viruses, Maize chlorotic mottle virus (MCMV) and a virus from the genus potyvirus. In a recent study, a Maize yellow dwarf virus-RMV (MYDV-RMV)-like polerovirus, was repeatedly detected in plants with maize lethal necrosis. Poleroviruses have a silencing suppressor, P0 protein, and the mechanism of suppression is poorly …


Genetic Diversity Of Potassium Ion Channel Proteins Encoded By Chloroviruses That Infect Chlorella Heliozoae, Carter Murry Mar 2020

Genetic Diversity Of Potassium Ion Channel Proteins Encoded By Chloroviruses That Infect Chlorella Heliozoae, Carter Murry

Honors Program: Senior Projects (Public)

Chloroviruses are large, plaque-forming, double-stranded DNA viruses that infect chlorella-like green algae that live in a symbiotic relationship with protists. Chloroviruses have a genome from 290 to 370 kb, and they encode as many as 400 proteins. One interesting feature of chloroviruses is that they encode a potassium ion (K+) channel protein named Kcv. K+ channels are essential proteins for life. They cross the membrane of the cell to quickly and selectively allow K+ in or out of the cell. This helps regulate the electrical charge of a cell which in turn helps control electrical signaling …


Identifying Essential Viral Genes Through Genomic Engineering, Amber Carroll Jan 2020

Identifying Essential Viral Genes Through Genomic Engineering, Amber Carroll

Mahurin Honors College Capstone Experience/Thesis Projects

Bacteria developed resistance to penicillin a mere four years after the groundbreaking antibiotic was first mass produced (Casadevall, 2010). Since then, the development of antibiotic-resistant bacteria has steadily risen, causing millions of difficult to treat infections annually. The challenge is to identify ways to combat these menacing microbes. Bacteriophages are viruses that infect bacteria and can potentially be used to eliminate deadly antibiotic-resistant bacteria. The number of sequenced bacteriophage genomes has increased tremendously over the past 10 years, but little is known about the function of most bacteriophage genes. The purpose of this study was to expand our understanding of …


Regulation Of Gene Expression Through Ribosome-Associated Proteins, Clare Margaret Miller Jan 2020

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 …


Biological And Computational Studies Of The Structure And Function Of Pul103, A Human Cytomegalovirus Tegument Protein, Ashley N. Anderson Jan 2020

Biological And Computational Studies Of The Structure And Function Of Pul103, A Human Cytomegalovirus Tegument Protein, Ashley N. Anderson

Wayne State University Dissertations

Human cytomegalovirus (HCMV) is an enveloped, single segment, double-stranded DNA virus. HCMV infection causes disease in immunocompromised (HIV patients, transplant recipients) and immunodeficient (fetuses, neonates) populations. Current treatments are effective but are either limited in use or can lead to organ damage and/or antiviral resistance, and no vaccines are available. Additional antiviral targets are needed. HCMV pUL103 is a potential antiviral target. pUL103 is a conserved herpesvirus protein present in the tegument, layer of proteins and RNA between the envelope and capsid of HCMV virions. pUL103 helps reorganize cellular secretory machinery (Golgi, endosomes) to form the cytoplasmic virion assembly compartment …


Role Of Topoisomerase Ii Alpha In Dna Topology And T Cell Responses During Chronic Viral Infections, Stella Chinyere Ogbu Dec 2019

Role Of Topoisomerase Ii Alpha In Dna Topology And T Cell Responses During Chronic Viral Infections, Stella Chinyere Ogbu

Electronic Theses and Dissertations

The clearance of viruses is largely dependent upon the activation of T cells to generate a robust immune response. However, host responses are suppressed during chronic viral infections. In this thesis, we explored the role of Top2α in DNA topology in individuals with chronic HBV, HCV, and HIV infections. We found that Top2α protein expression and activity were low in T cells derived from chronically virus-infected individuals compared to healthy subjects. Using CD4+ T cells treated with Top2α inhibitor or poisoner as a model, we demonstrated that Top2α inhibition disrupts the DNA topology, suppresses DNA repair kinase (ATM), and …


Development Of A Long-Acting Nanoformulation Of Dolutegravir For Prevention And Treatment Of Hiv-1 Infection, Brady Sillman May 2019

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 …