Virology Commons^™

Sars-Cov-2: Tale Of A Microscopic Murderer, Josiah P. Garner

Quest

Independent Study

Research in progress for BIOL1406: Biology for Science Majors I

Faculty Mentor: Amina Tassa, Ph.D.

I am delighted to introduce Josiah Garner’s “SARS-CoV-2: Tale of a Microscopic Murderer.” This independent study assignment explores the impact of a novel, deadly, and worldwide virus. The assignment also examines the fast development of vaccines to control the spread and reduce the symptoms of the virus.

Josiah’s paper focuses on the early history of the emergence of COVID-19, the world response, and vaccine development. He demonstrates critical thinking skills and effectively utilizes various research methods to obtain and communicate his information. Josiah …

Rna Virus-Mediated Changes In Organismal Oxygen Consumption Rate In Young And Old Drosophila Melanogaster Males, Eli Hagedorn, Dean Bunnell, Beate Henschel, Daniel Smith Jr, Stephanie Dickinson, Andrew Brown, Maria De Luca, Ashley Turner, Stanislava Chtarbanova

Research, Publications & Creative Work

Aging is accompanied by increased susceptibility to infections including with viral pathogens resulting in higher morbidity and mortality among the elderly. Significant changes in host metabolism can take place following virus infection. Efficient immune responses are energetically costly, and viruses divert host molecular resources to promote their own replication. Virus-induced metabolic reprogramming could impact infection outcomes, however, how this is affected by aging and impacts organismal survival remains poorly understood. RNA virus infection of Drosophila melanogaster with Flock House virus (FHV) is an effective model to study antiviral responses with age, where older flies die faster than younger flies due …

The Immune Modulation On Innate Immunity, From Pathogen Recognition To Fungal Clearance., Ko-Wei Liu

Dartmouth College Ph.D Dissertations

The human lung is not sterile but a complex environment with various microorganisms. Besides commensals in the lung, hundreds to thousands of individual microbiomes enter the lung every day but without causing the symptom. Host innate immunity plays an important role in maintaining homeostasis of the lung environment and as the first defense line against pathogens. Aspergillus fumigatus (A. fumigatus) is a saprophytic filamentous fungus that can cause human disease in immune compromised patients. However, with functional innate immunity, immune cells can quickly recognize pathogen associated molecular patterns (PAMPs) from A. fumigatus through pattern recognition receptors (PRRs). The activation of …

Proposing An Rna Interference (Rnai)-Based Treatment For Human Immunodeficiency Virus (Hiv) By Analyzing The Post-Transcriptional Gene Targeting Of Sars-Cov-2, Hepatitis C Virus, And A549 Lung Cancer Cells, Arjun Jagdeesh

Undergraduate Research Posters

Human Immunodeficiency Virus (HIV) is a retrovirus that infects CD4+ T cell lymphocytes in humans, leading to the development of Acquired Immunodeficiency Syndrome (AIDS) if left untreated. While current treatment methods, including antiretroviral combination treatments, effectively limit HIV replication, HIV can evade these treatments due to its high mutation rate. Long-term antiretroviral treatment can also be toxic to patients, meaning patients would benefit from a new mechanism of HIV treatment. RNA interference (RNAi) is an antiviral pathway found in mammals, plants, and insects that involves a small-interfering RNA that is incorporated into a protein complex called the RNA-induced Silencing Complex …

Investigating The Pi3k/Akt/Atm Pathway, Telomeric Dna Damage, T Cell Death, And Crispr/Cas9-Mediated Gene Editing During Acute And Chronic Hiv Infection, Sushant Khanal

Electronic Theses and Dissertations

Human Immunodeficiency Virus (HIV) infection initiates major metabolic and cell- survival complications. Anti-retroviral therapy (ART) is the current approach to suppress active HIV replication to a level of undetected viral load, but it is not a curative approach. Newer and sophisticated gene editing technologies could indeed be a potent antiviral therapy to achieve a clinical sterilization/cure of HIV infection. Chronic HIV patients, even under a successful ART regimen, exhibit a low-grade inflammation, immune senescence, premature aging, telomeric DNA attrition, T cell apoptosis, and cellular homeostasis. In this dissertation, we investigated CD4 T cell homeostasis, degree of T cell apoptosis, an …

Using A One Health Approach For The Assessment Of Rabies Control In Rural Victoria Falls, Zimbabwe, Ryan Lapenna

Electronic Thesis and Dissertation Repository

Rabies, a viral zoonotic disease, is widespread in Zimbabwe, with human fatalities reported annually in the country. To supplement the Government’s effort on rabies control, the Victoria Falls Wildlife Trust and Veterinarians for Animal Welfare Zimbabwe have joined forces to carry out dog rabies vaccinations in rural communities adjacent to the major tourist attraction of The Victoria Falls. A One Health approach was used to 1) determine the level of protective rabies antibodies among a sample of rural dogs and 2) collect information and describe the knowledge, attitudes, and practices related to rabies among dog owners. In 2020, blood was …

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 …

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 …

Insights To Protein Pathogenicity From The Lens Of Protein Evolution, Janelle Nunez-Castilla

FIU Electronic Theses and Dissertations

As protein sequences evolve, differences in selective constraints may lead to outcomes ranging from sequence conservation to structural and functional divergence. Evolutionary protein family analysis can illuminate which protein regions are likely to diverge or remain conserved in sequence, structure, and function. Moreover, nonsynonymous mutations in pathogens may result in the emergence of protein regions that affect the behavior of pathogenic proteins within a host and host response. I aimed to gain insight on pathogenic proteins from cancer and viruses using an evolutionary perspective. First, I examined p53, a conformationally flexible, multifunctional protein mutated in ~50% of human cancers. Multifunctional …

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 …

Meta-Analysis Of Transcriptomic Datasets For The Investigation Of Differential Expression In Hantavirus-Infected Human Tissue, John Krapohl

Annual Research Symposium

No abstract provided.

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 …

Evaluation Of Oasl And Herc5’S Role In The Non-Lytic Clearance Of Influenza A Virus From Club Cells, Steve Crisafulli

West Chester University Master’s Theses

Influenza A virus (IAV) is a highly infectious pathogen responsible for causing severe respiratory illness and death in humans and animals worldwide. Due to highly effective strategies to negate host antiviral defenses, IAV leads to the death of nearly all infected cells. Furthermore, IAV induces high levels of genome-damaging oxidative stress within infected cells and suppresses the cellular mismatch repair (MMR) mechanism, thereby inhibiting expression of key antiviral genes, which further contributes to cell death. However, recent studies have demonstrated that a subset of respiratory epithelial cells, called club cells, are able to non-lytically clear IAV and continue to survive …

Deciphering The Perpetual Fight Between Virus And Host: Utilizing Bioinformatics To Elucidate The Host's Genetic Mechanisms That Influence Jc Polyomavirus Infection, Michael P. Wilczek

Electronic Theses and Dissertations

JC polyomavirus (JCPyV) is a human-specific pathogen that infects 50-80% of the population, and can cause a deadly, demyelinating disease, known as progressive multifocal leukoencephalopathy (PML). In most of the population, JCPyV persistently infects the kidneys but during immunosuppression, it can reactivate and spread to the central nervous system (CNS), causing PML. In the CNS, JCPyV targets two cell types, astrocytes, and oligodendrocytes. Due to the hallmark pathology of oligodendrocyte lysis observed in disease, oligodendrocytes were thought to be the main cell type involved during JCPyV infection. However, recent evidence suggests that astrocytes are targeted by the virus and act …

Sodium Pyruvate Ameliorates Influenza A Virus Infection In Vitro And In Vivo, Jessica M. Reel

MSU Graduate Theses

Pyruvate is produced in duplicate at the end of glycolysis in addition to ATP and NADH. Pyruvate is the metabolite of choice in most cells, whether obtained exogenously or endogenously. Recently we found that the addition of pyruvate’s conjugate base, sodium pyruvate, to cell culture media dampened the immune response to influenza A virus (IAV) infection in cultured innate immune cells. Thus, I decided to investigate the mechanism and potential for treatment of IAV. In vitro using bone marrow derived macrophages that were infected with IAV we found that adding sodium pyruvate to the media decreased immune signaling pathways through …

B25: Generation And Characterization Of Sars-Cov-2 Spike Protein-Pseudotyped Lentivirus Particles For Use In Neutralizing Antibody Titer Testing Of Human Serum, Luis Sanchez

Annual Research Symposium

No abstract provided.

B16: Chikungunya Virus Time Course Infection Of Human Macrophages, Madison Gray, Israel Guerrero-Arguero, Antonio Solis Leal, Richard Robison, Brad Burges, Brett Pickett

Annual Research Symposium

Chikungunya virus (CHIKV) is an Alphavirus spread by Aedes spp. mosquitoes and is responsible for infecting 1.1 million people per year worldwide, including a large epidemic in the western hemisphere in 2014-2015. During the body’s immune response to CHIKV, human macrophages become infected after phagocytosis of CHIKV and undergo induced apoptosis, catalyzing the virus spread in the body. It is presently unclear what macrophage genes, functions, and intracellular signaling pathways are impacted during the early, intermediate, and late stages of CHIKV infection. Therefore we quantified the transcriptional response of human macrophage cells infected with CHIKV at two different timepoints.

Effectiveness Of Pathogen-Specific Passive Antibodies To Mitigate Infectious Diseases In Apis Mellifera, Tanner Nordseth

Honors Thesis

Honeybees (Apis mellifera) are widely recognized as a vital part of the global ecosystem and the world's food supply due to their pivotal role in the pollination of both natural and agricultural flora. Colony Collapse Disorder (CCD) is an emerging phenomenon characterized by a colony's worker bees deserting the hive and leaving the queen behind. This usually results in colony failure. CCD is a multifactorial issue, with many environmental stressors and pathogens playing a role. Deformed Wing Virus (DWV) has been identified as a leading cause in this phenomenon. Paenibacillus larvae (P. larvae) is another lethal pathogen that is …

A Workflow To Analyze Ethcd Mass Spectrometry Data For Studying Hiv Gp120 Glycosylation, Yingxue Sun

Electronic Thesis and Dissertation Repository

The great heterogeneity of HIV populations and richness of surface glycan clouds makes it difficult to locate a conserved and exposed protein epitope as an effective vaccine target. However, more than 80% new infections result from single transmitted founder (T/F) viruses. We set out to design a workflow to study the traits of T/Fs that allow for their superior infectivity, specifically, the glycosylation patterns of gp120, a subunit of HIV envelope protein responsible for binding to host cell receptors. Our main research methods include Western blot and mass spectrometry. Our current understanding of the mass spectrometry data indicates that our …

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 / …

Designing A Novel Hiv-1 Candidate Vaccine, Rahul Pawa

Electronic Thesis and Dissertation Repository

Currently no vaccine has been developed that can prevent the spread of HIV-1. During sexual transmission, a single viral variant called the Transmitted/Founder (T/F) purportedly with unique physical properties, establishes infection in 70-80% of individuals. Unlike previous studies that have tried to identify T/F viruses based on their structure glycan composition and amino acid sequence, we have analyzed the RNA sequences of HIV-1 to help identify T/F variants. Using a combination of both in silico data analysis and in vitro assays, we have identified that T/F viruses have higher numbers of immunostimulatory motifs than HIV virions that fail to infect. …

A Role Of Ubiquitin Regulatory X-Domain Containing Proteins (Ubxn6) In Antiviral Immunity, Harshada Ketkar, Harshada Ketkar

NYMC Student Theses and Dissertations

The roles of UBXNs in the regulation of antiviral immune responses have not been much explored. Previous work in our lab identified UBXN1 as a negative regulator of the retinoic acid-inducible gene-I (RIG-I) like receptors (RLR) pathway and UBXN3B as a positive regulator of stimulator-of-interferon Genes (STING) -mediated immune responses. In this study, I aimed to determine the member of UBXNs as a positive regulator of ribonucleic acid (RNA) virus infection-induced innate immune responses. By using an interferon stimulated response element (ISRE)-driven luciferase reporter assay that monitors the activity of type I/III interferon (IFN)-induced janus kinase (JAK) - signal transducer …

Endogenous, Controlled Expression Of Anti-Hiv-1 Broadly Neutralizing Antibody, Darshit Patel

Electronic Thesis and Dissertation Repository

Recently, researchers have identified a number of anti-HIV broadly neutralizing antibodies (bNAbs), such as VRC01 and N6, capable of targeting a broad range of HIV-1 strains. Passive immunization using these patient-derived bNAbs could provide temporary protection but are limited by the short antibody half-life. While current gene transfer technology allows sustained bNAb expression, it lacks the ability to control bNAb production in vivo resulting in possible autoimmunity. To address this issue of achieving controlled bNAb expression in vivo, we hypothesize that bNAb expression from transduced Flu-specific B cells can be activated and modulated by subsequent Flu immunizations in the …

Elucidating Immune Signaling Of Influenza A Virus And Aspergillus Fumigatus Co-Infections Through Pioneered Model Development, Meagan Danyelle Rippee-Brooks

MSU Graduate Theses

Bacterial co-infections with influenza A virus (IAV) are extremely serious and life-threatening. However, there exists limited understanding about the importance of fungal infections with IAV. Clinical case reports indicate that fungal co-infections do occur and suggest the IAV pandemic of 2009 had a propensity to predispose patients to secondary fungal infections more than previous IAV strains. IAV-fungal co-infections are marked by high mortality rates of 47 to 61% in previously healthy individuals between the ages of 20 and 60. Yet, the variables involved in this co-infection remain undetermined. I achieved effective recapitulation of this co-infection using a C57Bl/6 murine (mouse) …

Iiv-6 Inhibits Nf-Kappab Responses In Drosophila, Cara C. West, Florentina Rus, Ying Chen, Anni Kleino, Monique Gangloff, Don B. Gammon, Neal S. Silverman

Neal Silverman

The host immune response and virus-encoded immune evasion proteins pose constant, mutual selective pressure on each other. Virally encoded immune evasion proteins also indicate which host pathways must be inhibited to allow for viral replication. Here, we show that IIV-6 is capable of inhibiting the two Drosophila NF-kappaB signaling pathways, Imd and Toll. Antimicrobial peptide (AMP) gene induction downstream of either pathway is suppressed when cells infected with IIV-6 are also stimulated with Toll or Imd ligands. We find that cleavage of both Imd and Relish, as well as Relish nuclear translocation, three key points in Imd signal transduction, occur …

Stalking Flu: Development And Characterization Of A Broadly Neutralizing Monoclonal Antibody Targeting The Influenza Hemagglutinin Stem, Elizabeth Newman

NYMC Student Theses and Dissertations

Seasonal epidemics caused by influenza A viruses (IAV) result in an estimated 290,000- 650,000 deaths worldwide each year (17). While antivirals targeted to influenza exist, resistance to these drugs is increasing and regular vaccination remains the most effective way to prevent infection (26, 73, 99). However due to the persistence of antigenic drift and shift, influenza vaccines must be updated each season and antigenic mismatches can reduce efficacy (24, 118). Immunity to influenza either from vaccination or infection is principally mediated by antibodies generated to one of its major surface proteins, Hemagglutinin (HA). HA is a homotrimer, each monomer HA0 …

A Case-Study Approach To Investigate Transmission, Co-Infection, And Clinical Sequelae During Epidemics Of Dengue And Ebola Virus Disease, Jennifer Elizabeth Giovanni

LSU Doctoral Dissertations

From within their ecologic niches, zoonotic viruses emerge from animal reservoirs into the edges and centers of human habitation to exploit opportunities for unabated transmission within immunologically–naïve populations. Our understanding of where, in whom, and how these viruses emerge is under direct challenge, driving the evolution of modern infectious disease epidemiology within a rapidly-connected global community. The studies presented herein are based on analyses of both aggregate and case-level data, which, we argue, provide unique insight into the complexities of transmission, co-infection, and clinical sequelae occurring within, and arising from, epidemics of emerging zoonotic viruses. In Chapter II, we investigate …

Hiv-1 Group M Subtype Fitness, Disease Progression, And Entry Efficiency, Colin M. Venner

Electronic Thesis and Dissertation Repository

Human immunodeficiency virus type 1 (HIV-1) emerged in the human population shortly after the turn of the 19th century. Distribution of HIV-1 across the globe over the past 30–35 years can be traced to founder events with primordial HIV strains from sub-Saharan Africa. Even considering the burden of HIV in Africa, our knowledge of HIV-1 disease is still largely limited to subtype B HIV-1, a strain responsible for 3 million infections in North America and Europe as compared to the 33 million that are infected with HIV-1 subtypes A, C, D, and circulating and unique recombinant forms.

This dissertation analyzes …

Distribution Of Dengue And Zika Virus Igg Immunoglobulin, Madison Smith, Awadalkareem Adam, Anuja Mathew

Senior Honors Projects

Introduction. Dengue Virus (DENV) and Zika Virus (ZIKV) are viruses that belong to the Flavivirus family. They are transmitted by the Aedes aegypti species of mosquitoes. Infection with DENV can result in no symptoms, mild symptoms which include fever, rash, and headache (dengue fever) or more severe symptoms which include hemorrhage, dengue hemorrhagic fever (DHF) and shock, dengue shock syndrome (DSS). ZIKV, until recently caused mild disease but an outbreak in Brazil was associated with fetal complications such as microcephaly or Guillain-Barré syndrome in adults. Due to the similarity between ZIKV and DENV, antibodies (Abs) generated in humans to these …

Congenital Zika Virus Infection In Immunocompetent Mice Causes Postnatal Growth Impediment And Neurobehavioral Deficits, Amber M. Paul, Dhiraj Acharya, Biswas Neupane, E. Ashley Thompson, Gabriel Gonzalez-Fernandez, Katherine M. Copeland

Publications

A small percentage of babies born to Zika virus (ZIKV)-infected mothers' manifest severe defects at birth, including microcephaly. Among those who appeared healthy at birth, there are increasing reports of postnatal growth or developmental defects. However, the impact of congenital ZIKV infection in postnatal development is poorly understood. Here, we report that a mild congenital ZIKV-infection in pups born to immunocompetent pregnant mice did not display apparent defects at birth, but manifested postnatal growth impediments and neurobehavioral deficits, which include reduced locomotor and cognitive deficits that persisted into adulthood. We found that the brains of these pups were smaller, had …