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Full-Text Articles in Virology

Identifying The Role Of Human Dna Polymerase Delta During Human Cytomegalovirus Genome Synthesis, Rachel Laree Dansereau May 2026

Identifying The Role Of Human Dna Polymerase Delta During Human Cytomegalovirus Genome Synthesis, Rachel Laree Dansereau

Dartmouth College Master’s Theses

Human cytomegalovirus (HCMV) is a large double stranded DNA virus and member of the Herpesviridae family. Like all herpesviruses, HCMV presents with characteristics of persistent, lifelong infections that transition between lytic and latent states. The replication of the viral genome is traditionally thought to occur by a rolling circle mechanism, but this model is supported by little evidence. It is known that HCMV actively recruits several host proteins to viral replication compartments (RCs), including proteins involved in the DNA damage response (DDR). The exact mechanisms of how these proteins are used and in what ways they help the virus remain …


Characterization Of The Antiviral Activity Of Mouse Schlafen Proteins, Wendy Paola Alvarez Leal May 2026

Characterization Of The Antiviral Activity Of Mouse Schlafen Proteins, Wendy Paola Alvarez Leal

Open Access Theses & Dissertations

The goal of this work was to characterize the anti-viral role of mouse Schlafen8 and Schlafen9. Expression of these proteins is induced by type I interferon in response to viral infections. Importantly, their human functional orthologs exhibit anti-viral functions, and the structural element required for these activities are conserved in Schlafen8 and Schlafen9. Therefore, it is expected that these proteins will also impair viral replication. An important limitation in this field is that the anti-viral function of human SLFNs has been evidenced only in in vitro cellular models. No informative mutations have been described in human populations so far. Thus, …


Beyond Attachment: Endolysosomal Determinants Of New World Arenavirus Entry And Fusion, Cassandra E. Thompson Apr 2026

Beyond Attachment: Endolysosomal Determinants Of New World Arenavirus Entry And Fusion, Cassandra E. Thompson

Arts & Sciences Graduate Student Theses and Dissertations

Arenaviruses are enveloped, negative-sense RNA viruses maintained in rodent reservoirs and transmitted to humans through exposure to aerosolized rodent excreta, where they can cause severe and sometimes fatal disease. The geographic distribution of arenaviruses reflects the range of their rodent reservoirs, resulting in the classification into Old World and New World groups, with New World arenaviruses further subdivided into clades A–D. Viral entry is the first step of infection and a major determinant of host range, tissue tropism, and zoonotic potential. Further, viral entry is a tightly regulated, multistep process that couple’s receptor engagement with intracellular trafficking and pH-dependent membrane …


Structural Insights Into Host-Pathogen Interactions Of Coronaviruses And Alphaviruses, Lucas Adams Mar 2026

Structural Insights Into Host-Pathogen Interactions Of Coronaviruses And Alphaviruses, Lucas Adams

Arts & Sciences Graduate Student Theses and Dissertations

The co-evolution of virus and host may partly be understood in terms of “cross-recognition”; that is, as a virus evolves to recognize and infiltrate a suitable cellular environment, the host reciprocally has evolved to recognize and thwart such an invasion. While this interplay is complex, audacious structural biologists may reduce it to discrete physical interactions between the virus and specific host factors, such as cognate receptors (i.e., viral recognition of host) or antibodies (i.e., host recognition of virus). These interactions underlie basic features of viral infection, including cellular tropism and antiviral immunity, as well as critical phenomena of viral evolution, …


The Role Of Autophagy In Intestinal Infection In Mice And C. Elegans, Gowri Kalugotla Mar 2026

The Role Of Autophagy In Intestinal Infection In Mice And C. Elegans, Gowri Kalugotla

Arts & Sciences Graduate Student Theses and Dissertations

Although autophagy, which is the process by which cells reallocate nutrients and eliminate unwanted materials, has been studied for decades, the connections between autophagy, inflammation, and viral immunity are still under investigation. Our studies focus on two genes: murine Epg5, which is involved in fusion of the autophagosome and lysosome, and C. elegans atg-3, which is important for the elongation of the phagophore. Here, we find that Epg5 mutation protects against enteric viruses including norovirus and rotavirus. We identify IFN- responsive genes as a key alteration and observe that Epg5 mutant mice exhibit substantial alterations in the intestinal microbiota. Surprisingly, …


Uncovering Hidden Features Of Copyback Viral Genomes, Sarah Pye Mar 2026

Uncovering Hidden Features Of Copyback Viral Genomes, Sarah Pye

Arts & Sciences Graduate Student Theses and Dissertations

Copyback viral genomes (cbVGs) are truncated non-protein coding viral genomes produced when an RNA virus polymerase detaches from the replication template and resumes elongation downstream, copying back a sequence complementary to the nascent strand. cbVGs can stimulate antiviral immunity and compete for viral proteins to suppress virus replication, but technical limitations of PCR-based approaches have painted an incomplete picture of the diverse cbVG populations generated during infection. Here, we sought to improve our understanding of cbVG molecular structure by harnessing long-read RNA sequencing tools. To do this, we developed a robust and reliable pipeline to sequence and analyze native full-length …


Investigating Host Factors In Coronavirus Assembly And Egress, Surovi Binte Sharmin Mohona Jan 2026

Investigating Host Factors In Coronavirus Assembly And Egress, Surovi Binte Sharmin Mohona

Dissertations

Coronavirus (CoV) structural proteins congregate at the ER-Golgi intermediate compartments (ERGIC) prior to virus budding into the organelle lumen. Subsequent trafficking and fusion of virus-containing, ERGIC-derived vesicles then release nascent viruses from infected cells. Our findings in this dissertation illuminate mechanisms by which CoV structural proteins coalesce at the virus assembly and budding sites. The cytoplasmic tails of all CoV spike (S) glycoproteins contain variants of a consensus KxKxx coatomer-binding motif. Host coatomer complexes facilitate retrograde trafficking of client cargo proteins via recognition of such motifs. Utilizing reverse genetics methodologies, we introduced variations in the S coatomer motif in a …


The Geminivirus Al2 Protein Interacts With Host Proteins Involved In The Plant Antiviral Response, Pheobean Atieno Odongo Jan 2026

The Geminivirus Al2 Protein Interacts With Host Proteins Involved In The Plant Antiviral Response, Pheobean Atieno Odongo

Graduate Research Theses & Dissertations

Geminiviruses are economically important plant DNA viruses infecting a broad range of plant species and causing devastating crop diseases, resulting in up to 100% crop loss. As a result of these heavy losses on food and cash crops, these viruses represent a new threat to global food security and sustainability. In this research, I use Tomato golden mosaic virus (TGMV) to study host-virus relationships with an overall goal of developing sustainable and eco-friendly crop resistance. TGMV belongs to the Geminivirus subgroup, Begomovirus, that is characterized by a split genome consisting of two single-stranded circular DNAs. The TGMV genome encodes proteins …


Surveillance Of A Novel Vesivirus Discovered In An Urban Mephitis Mephitis Population, Amanda E. Diggins Jan 2026

Surveillance Of A Novel Vesivirus Discovered In An Urban Mephitis Mephitis Population, Amanda E. Diggins

Honors Theses and Capstones

Caliciviridae is a family of non-enveloped, positive-sense, single stranded RNA viruses, including eleven defined genera that contain important pathogens of humans and animals. Within the Caliciviridae family, the genus Vesiviridae includes feline calicivirus, a leading cause of upper respiratory disease in cats, and vesicular exanthema of swine virus, a historical disease of domestic swine that has now been implicated in several marine mammal vesicular diseases, one of which has been confirmed zoonotic. Urban landscapes create a unique environment for rapid intra- and interspecies transmission of viruses. Clustered resources attract high-density populations of synanthropic wildlife species, increasing spatial overlap and heightening …


Characterizing The Human Metapneumovirus Matrix Protein And Its Role In Infection, Chase J. Heim Jan 2026

Characterizing The Human Metapneumovirus Matrix Protein And Its Role In Infection, Chase J. Heim

Theses and Dissertations--Molecular and Cellular Biochemistry

Human metapneumovirus (HMPV) causes severe respiratory tract infections in all cohorts, but especially in vulnerable groups such as children, older adults, and the immunocompromised. The matrix (M) protein of HMPV, like the M proteins of other members of the Mononegavirales order, is involved in virus assembly and budding. However, other functions of the HMPV M protein have yet to be elucidated. To investigate these various functions of the M protein, we used a peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO) antisense agent designed to block translation of the M gene to reduce M expression during infection. Treatment with varying concentrations of an …


Interactions Of Complement With Paramyxovirus Persistently Infected Cells, Nasser N. Yousef Jan 2026

Interactions Of Complement With Paramyxovirus Persistently Infected Cells, Nasser N. Yousef

Graduate Studies Theses and Dissertations 2026

Persistent RNA virus infections (PI) are often characterized by extended viral shedding and maintained cycles of inflammation. We have an incomplete understanding of interactions between exogenous and cell intrinsic Complement (C') factors and paramyxovirus PI cells. Parainfluenza virus 5 (PIV5) acute infected (AI) cells can be recognized and lysed by exogenous C’ factors, but PI cells become resistant to C’-mediated lysis. We hypothesized that the relative sensitivity of AI and PI cells to C’ lysis is correlated with viral glycoprotein expression on the surface of cells. PI cells display lower levels of viral glycoprotein expression compared to AI cells. Pharmacological …


The Effect Of The Affordable Care Act Medicaid Expansion On The Risk Of Hospital Closure And Adolescent Hpv Immunization In Rural Counties, Juliette Des Rosiers Jan 2026

The Effect Of The Affordable Care Act Medicaid Expansion On The Risk Of Hospital Closure And Adolescent Hpv Immunization In Rural Counties, Juliette Des Rosiers

Scripps Senior Theses

From 2005 to 2025, over 200 rural hospitals shut their doors, often citing increased operational costs, staffing shortages, low patient volume, regulatory barriers, financial challenges exacerbated by the COVID-19 pandemic, and uncompensated care as common contributors to the closures. Rural patients are often referred by their primary care physician to a hospital for regular immunizations, since smaller clinics have less capacity to provide immunizations due to a shortage of pediatricians and limited vaccine stock. A crucial vaccine that is not required by schools and underutilized in rural areas is that against human papillomavirus (HPV), a virus that infects cutaneous and …


Exploring The Application Of Wastewater Monitoring To Determine The Prevalence And Diversity Of Influenza On The Campus Of West Virginia University, Lakyn Renee Sanders Jan 2026

Exploring The Application Of Wastewater Monitoring To Determine The Prevalence And Diversity Of Influenza On The Campus Of West Virginia University, Lakyn Renee Sanders

Graduate Theses, Dissertations, and Problem Reports (ETD)

Influenza viruses (IV) affect populations globally, with the World Health Organization (WHO) estimating that IV are responsible for an estimated 3-5 million infections and 290,000 – 650,000 deaths annually1–3. More specifically, the 2019-2020 IV season is associated with an estimated 38 million illnesses and 22,000 deaths in the United States alone4. IV are rapidly spread between individuals through direct contact with infected individuals, contaminated surfaces, or aerosolized virus particles2. Traditional IV infection monitoring relies on clinical screening of patients presenting influenza-like symptoms, commonly through the use of multi-target panel tests such as the BioFire …


Viral And Host Cell Determinants Of Resistance To Complement-Mediated Killing During Parainfluenza Virus Type 5 Infection, Jenna R. Aquino Jan 2026

Viral And Host Cell Determinants Of Resistance To Complement-Mediated Killing During Parainfluenza Virus Type 5 Infection, Jenna R. Aquino

Graduate Studies Theses and Dissertations 2026

RNA viruses are a major global public health concern due to high mutation rates, zoonotic potential, and immune evasion. Parainfluenza virus 5 (PIV5) can establish persistent infections (PIs) despite encountering innate immune responses, including the complement (C′) system. RNA virus replication produces defective interfering particles (DIPs) containing truncated defective viral genomes (DVGs) that depend on standard (STD) virus for replication. DVGs are increasingly detected in natural infections and modulate type I interferon (IFN-I), but their role in the C′ system is unclear. We investigated how DVGs affect C′-mediated lysis during PIV5 infection using real-time in vitro cell viability assays. C′ …


Advancing The Virus Diagnostic Toolkit: Development Of Accurate And Reliable Artificial Virus-Mimicking Positive Controls And Crispr-Based Detection, Habeeb Yinka Atanda Dec 2025

Advancing The Virus Diagnostic Toolkit: Development Of Accurate And Reliable Artificial Virus-Mimicking Positive Controls And Crispr-Based Detection, Habeeb Yinka Atanda

Graduate Theses and Dissertations

Accurate and reliable detection of plant viruses is critical for protecting berries and other economically important crops. Yet diagnostic programs face persistent challenges with positive control availability, biosafety concerns, and specificity limitations. This thesis advances the diagnostic toolkit for berry viruses through three complementary innovations that address fundamental gaps in current detection methodologies. First, this research developed and validated virus-mimicking artificial positive controls (ViMAPCs) for diverse viruses affecting berry crops for endpoint PCR applications. ViMAPCs incorporate size differentiation, which enables immediate visual gel band discrimination between control and natural infection signals. Amplification efficiency analysis demonstrated close correspondence with true-positive controls …


Increasing Pediatric Hpv Vaccination Rates, Brooke A. Nicholas Nov 2025

Increasing Pediatric Hpv Vaccination Rates, Brooke A. Nicholas

Dissertations

Increasing Pediatric HPV Vaccination Rates

Abstract

Problem: The human papillomavirus (HPV) is a sexually transmitted infection that affects more than 80% of the population within the United States (Eisenhauer et al., 2020). HPV can develop into cervical, anogenital, and oropharyngeal cancers (Eisenhauer et al., 2020). About 4,000 individuals die from cervical cancer alone each year (O’Leary, 2022). The HPV vaccine, though recommended by the ACIP and AAP, is below national vaccination rates in comparison to other vaccines (O’Leary, 2022).

Methods: This quality improvement project is a non-randomized controlled trial that observed HPV vaccine dose completion rates for patients aged 9-14 …


Enhancing Preparedness: A Genetic Study Of Sar-Cov-2 And Other Microbial Public Health Threats In Wastewater From A College Town, Christian N. Hutchinson Sep 2025

Enhancing Preparedness: A Genetic Study Of Sar-Cov-2 And Other Microbial Public Health Threats In Wastewater From A College Town, Christian N. Hutchinson

Master's Theses

Problem

The SARS-CoV-2 (COVID-19) pandemic revealed both the systemic vulnerabilities of our healthcare system as well as the importance of timely, localized data for informing public health responses. Traditional testing approaches were essential but often failed to capture the full extent of viral spread, especially in those with mild or asymptomatic conditions that relied on at home testing. This underreporting hindered effective allocation of resources and made developing effective intervention strategies difficult. We also realized the potential for wastewater surveillance to be applied to tracking antimicrobial resistance gene markers. Taken together, this approach should have important implications for improving public …


Role Of Cellular Proteins In The Regulation Of Herpes Simplex Virus Type 1 Gene Expression And Dna Replication, Joseph R. Heath Aug 2025

Role Of Cellular Proteins In The Regulation Of Herpes Simplex Virus Type 1 Gene Expression And Dna Replication, Joseph R. Heath

Electronic Theses and Dissertations

Herpes simplex virus type 1 (HSV-1) is a ubiquitous human pathogen that infects the majority of the human population. To facilitate infection, this virus relies on a combination of host and viral factors. Previous studies have revealed a number of host proteins that associate with the HSV-1 genome throughout infection but their putative role(s) in this process remain undefined. This study aims to examine two such proteins to determine their contributions to HSV-1 gene expression and DNA replication. The first of these factors is Ints3, a subunit of the Integrator complex. This protein complex functions in transcription regulation, and Ints3 …


Identification Of Host Nuclear Factors Exploited By Kshv Lana To Maintain Latency, Anandita Ghosh Jun 2025

Identification Of Host Nuclear Factors Exploited By Kshv Lana To Maintain Latency, Anandita Ghosh

USF Tampa Graduate Theses and Dissertations

Kaposi’s Sarcoma Associated Herpes Virus (KSHV or HHV-8) is a γ-herpesvirus implicated in multiple lymphoproliferative human cancers and immune dysregulatory diseases. Like other herpesviruses, KSHV has a biphasic mode of infection primarily orchestrated by two viral proteins: the Latency-Associated Nuclear Antigen (LANA), which promotes viral persistence through latency, and the Replication and Transcription Activator (RTA), which triggers lytic reactivation. During latency, the KSHV genome exists as a highly heterochromatinized, extrachromosomal episome in the nucleus, which can be reverted to euchromatin in response to certain stimuli, like stress. KSHV has evolved to exploit numerous host proteins to orchestrate its lifecycle, especially …


Investigating The Consequences Of Conjugated And Secreted Isg15 On Coronavirus Pathogenesis, Mudassir Syed Ali Jun 2025

Investigating The Consequences Of Conjugated And Secreted Isg15 On Coronavirus Pathogenesis, Mudassir Syed Ali

Dissertations

Coronaviruses have evolved a breadth of mechanisms to antagonize host innate immune responses. One widely studied mechanism is the ability to deconjugate ISG15 from target proteins in a process called deISGylation, which is catalyzed by the papain-like protease (PLP) domain of viral non-structural protein (nsp) 3. Since PLP activity is required for viral replication, it has been challenging to generate an infectious virus with a PLP that maintains protease activity but has lost deISGylase activity. In this study, we generated a chimeric MHV-A59 with its PLP2 domain replaced with that of the human coronavirus HKU1, which has been documented to …


Assessing The Efficiency Of Methotrexate (Mtx) As An Antiviral Drug Against Gammaherpes Virus Replication, Yennifer A. Gaspar Garcia May 2025

Assessing The Efficiency Of Methotrexate (Mtx) As An Antiviral Drug Against Gammaherpes Virus Replication, Yennifer A. Gaspar Garcia

Honors Projects

It is estimated that ~15% of all cancers are caused by oncogenic virus infections. Two of the top seven cancer-causing human viruses are members of the gammaherpesvirus family: Epstein Barr Virus (EBV) and Kaposi’s Sarcoma Herpesvirus (KSHV). Our lab uses Murine Herpesvirus 68 (MHV-68), a mouse gammaherpesvirus with shares significant genetic homology to KSHV and EBV, as a model system to understand how gammaherpesviruses alter the metabolism of their host during lytic infection to promote their replication. We recently metabolically profiled MHV-68 infected host cells at various time points during the lytic infectious cycle. Our data showed nucleotide metabolism is …


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 May 2025

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) …


Sars-Cov-2 Modulates Pla2g2d/Pgd2 Signaling To Manipulate Host Immune Response To Increase Disease Severity., Dante L. Hamiel May 2025

Sars-Cov-2 Modulates Pla2g2d/Pgd2 Signaling To Manipulate Host Immune Response To Increase Disease Severity., Dante L. Hamiel

Electronic Theses and Dissertations

Background: Previous studies suggested that SARS-CoV-2 infection could cause diverse immune and metabolic dysregulations, although the underlying mechanisms remain poorly understood. In addition, viruses may escape the immune response by modulating cellular metabolism, mitochondria, and protein functions indicating that immune or metabolic components may represent novel targets for anti-viral strategies. However, whether immune and metabolic disorders interact or affect each other waits to be determined. On the other hand, previous investigations identified the critical roles of a cell membrane-bound phospholipase PLA2G2D and its downstream products PGD2 in regulating the metabolism and inflammation in respiratory system. More importantly, …


Expanding Inducible Epithelial Resistance Against Pneumonia: Novel Virus, Novel Receptor, Michael Longmire May 2025

Expanding Inducible Epithelial Resistance Against Pneumonia: Novel Virus, Novel Receptor, Michael Longmire

Dissertations and Theses (Open Access)

Pneumonia is the leading infectious cause of death worldwide and presents a continuing risk among immunocompromised patients. Our work has been focused for many years on the phenomenon of inducible epithelial resistance, where activation of the innate immune response in the airway epithelium is necessary and sufficient to produce a pathogen-killing but self-protective environment to prevent severe disease. Inducible resistance is pathogen-agnostic and has been demonstrated against an array of respiratory infections. We achieve this using a combination of pattern recognition receptor agonists – Pam2CSK4 and ODN M362 being the current formulation – which produce synergistic levels of pathogen reduction …


Seasonal Detection Of Coliphages In Freshwater Bodies At Coastal Carolina University, Ella Caldwell Apr 2025

Seasonal Detection Of Coliphages In Freshwater Bodies At Coastal Carolina University, Ella Caldwell

Honors Theses

Bacteriophages, commonly referred to as phages, are non-living viruses that only infect bacteria. As the most abundant biological entities on Earth, understanding their role in regulating microbial populations is essential. This ongoing research aims to identify naturally occurring bacteriophages that could effectively control bacteria blooms. The primary objective of this study is to detect coliphages on Coastal Carolina University's campus and determine their viral families. Coliphages are a subgroup of bacteriophages that specifically infect coliform bacteria. Water samples were collected across multiple sites on campus, and polymerase chain reaction (PCR) was employed to amplify the viral DNA from the potential …


The Isolation And Characterization Of Acidovorax And Brevundimonas Bacteriophages With Preliminary Biocontrol Study On Arabidopsis Thaliana, Minh Quynh N. Vu Apr 2025

The Isolation And Characterization Of Acidovorax And Brevundimonas Bacteriophages With Preliminary Biocontrol Study On Arabidopsis Thaliana, Minh Quynh N. Vu

Senior Theses

As antibiotic-resistance becomes an increasing global concern, researchers are looking for alternatives to combat phytopathogenic rhizobacteria – one of which is through the application of phage biocontrol. To elucidate the complex tripartite relationships between phage, bacteria and plant interactions, nine novel phages were isolated from potential phytopathogenic strains of Acidovorax (RBW13) and Brevundimonas (RBW18). These phages were isolated from root samples obtained from the Rocky Branch Creek and the Broad River located in Columbia, SC. Using Pulsed-Field Gel Electrophoresis (PFGE), we identified seven “medium sized” phages (~40 kbp), one “large-sized” phage (~200 kbp), and one “small-sized” phage ( < 25 kbp). Three phages were determined to be lambda-like due to their “ladder-building” patterns on PFGE. Although spot-tests revealed that all phages seemed to have broad host ranges that spanned over multiple genera, plaque-formations must be observed in future experiments to determine if these phages can infect their hosts productively. Preliminary in planta experiments were performed on Arabidopsis thaliana …


Investigating The Proviral And Immunogenic Effects Of Sars-Cov-2 Accessory Protein 7a, Grant Michael Hawkins Mar 2025

Investigating The Proviral And Immunogenic Effects Of Sars-Cov-2 Accessory Protein 7a, Grant Michael Hawkins

Dissertations

SARS-CoV-2 and related sarbecoviruses encode a set of accessory proteins (3a, 3b, 6, 7a, 7b, 8, 9b, and 10) that control host responses to infection and promote virus growth. Of these accessory proteins, 7a is set apart by its intracellular localization near coronavirus (CoV) budding sites and its incorporation into secreted virions. Initial studies utilizing a virus-like particle (VLP) system identified significant proviral effects mediated by 7a, but the system lacked the context of an actual CoV infection. To investigate 7a functions during CoV infections, we constructed recombinant Mouse Hepatitis Viruses (rMHV strain A59) that express 7a genes. Comparative infections …


The Design, Construction, And Testing Of Mrna Vaccine Against Equine Herpes Virus, Bhawana Devkota Mar 2025

The Design, Construction, And Testing Of Mrna Vaccine Against Equine Herpes Virus, Bhawana Devkota

LSU Master's Theses

Equine Herpesvirus-1 (EHV 1) is a worldwide significant pathogen that causes respiratory illness, abortion, and neurological disorders in equine. Current vaccines, including live attenuated, inactivated, and subunit platforms, do not prevent viral latency, mucosal shedding, or cross-strain immunity, requiring alternative approaches. To address these gaps, this project explores the design, synthesis, and in vitro testing of an mRNA vaccine targeting immunogenic EHV 1 glycoprotein (gB, gC, gD, gG, and gM). Epitopes were computationally predicted using the Immune Epitope Database (IEDB), codon-optimized for Bos taurus, and cloned into pUCIDT vectors using SP6/T7 promoters. In vitro transcription (IVT) used nucleotide modifications …


Discerning The Role Of Microtubule Acetylation During Hiv-1 Infection, Drew Michael Lichon Jan 2025

Discerning The Role Of Microtubule Acetylation During Hiv-1 Infection, Drew Michael Lichon

Dissertations

The host-pathogen interactions underlying Human Immunodeficiency Virus type 1 (HIV-1) infection are complex and involve the exploitation of host cellular machinery. This thesis investigates the roles of dynein adaptors, microtubule acetylation, and TRIM69-mediated restriction in HIV-1 infection. Through a series of detailed experiments, we explore how HIV-1 utilizes multiple dynein adaptors, such as BICDR1 and Hook3, for intracellular transport, and reveal that these adaptors are critical for efficient viral trafficking. Conversely, the knockdown of Ninein surprisingly enhances HIV-1 infectivity, suggesting a nuanced regulatory role for this adaptor in viral transport. Further, this thesis challenges the prevailing paradigm that microtubule acetylation …


Investigating The Role Of The Nsp15 Amino-Terminal Domain In Nsp15 Function, Viral Replication, And Pathogenesis, Monika Evdokimova Jan 2025

Investigating The Role Of The Nsp15 Amino-Terminal Domain In Nsp15 Function, Viral Replication, And Pathogenesis, Monika Evdokimova

Dissertations

Identifying conserved mechanisms used by viruses to delay host innate responses can reveal potential targets for antiviral therapeutics. Here, we investigated coronavirus nonstructural protein 15 (nsp15), which encodes a highly conserved endoribonuclease (EndoU). EndoU functions as an immune antagonist by limiting the accumulation of viral replication intermediates that would otherwise be sensed by the host. Despite being a promising antiviral target, it has been difficult to develop small molecule inhibitors that target the EndoU active site. We generated nsp15 mutants of SARS-CoV-2 and mouse coronavirus MHV-A59 and identified conserved residues within the amino-terminal domain that are required for EndoU activity. …