Virology Commons^™

Type 2 Bovine Viral Diarrhea Virus NPro Suppresses Type I Interferon Pathway Signaling In Bovine Cells And Augments Bovine Respiratory Syncytial Virus Replication, Abdulrahman Abdulaziz A. Alkheraif

School of Veterinary and Biomedical Sciences: Dissertations, Theses, and Student Research

Bovine viral diarrhea virus (BVDV) and bovine respiratory syncytial virus (BRSV) infections contribute to the bovine respiratory disease complex (BRDC), which is a multi-factorial disorder involving co-infections of viruses and bacteria including mycoplasma. BRDC causes great economic losses to the United States feedlot industry. BVDV infection induces immunosuppression in infected animals. BVDV N^pro binds and degrades the transcription factor interferon regulatory factor-3 (IRF-3) and effectively blocks type I interferon (type I IFN) expression in host cells. BRSV nonstructural proteins, NS1 and NS2, block activation of IRF-3. In calves, concurrent infection with BVDV and BRSV resulted in more severe clinical …

Investigation Into The Causes And Severity Of The 1918 Influenza Pandemic, Alex T. Freedenberg

The Review: A Journal of Undergraduate Student Research

The 1918 Influenza outbreak is regarded as one of the worst pandemics in human history due to its widespread effects across the globe and its high death rate. This death rate was unusual among influenza infections as most strains do not cause the amount of death that is seen in this outbreak, with 20 million dead as a conservative estimate and 100 million by other estimations. This pandemic was not very well contained for a plethora of reasons. Two main reasons are that it came at a time when understanding viral mechanics still escaped medical professionals, and due to the …

Role Of Mucin 19 In The Respiratory Tract, Kaitlin Mcbride

LSU Master's Theses

Human metapneumovirus (HMPV) is a negative sense, single stranded RNA virus belonging to the Pneumoviridae family, and represents an important pathogen that causes severe respiratory disease worldwide. There is currently no vaccine against HMPV, so it is important to study the aspects of the immune response induced by HMPV. Because infiltration of mucus is a hallmark of HMPV infection, it is warranted to study the role of mucus in the disease process. Mucin proteins make up the major component of mucus and can be found within the airway and lungs. Previous work from our laboratory demonstrated a high upregulation of …

Surveillance Of South Dakota Mosquito Abundance, Infection Rate, And Insecticide Susceptibility, Geoffrey P. Vincent

Electronic Theses and Dissertations

The aim of this dissertation was to survey and evaluate the abundance, infection rate, and insecticide susceptibility of mosquito fauna present in South Dakota. Mosquito surveillance has been conducted across South Dakota to record and track potential West Nile virus (WNV) vectors from 2004 to 2017. The nuisance mosquito Aedes vexans was found to be the most abundant species overall in the state and most abundant in many of the regions. The WNV vector, Culex tarsalis, was found to be the second most abundant mosquito and the most abundant vector mosquito across the state. However, geospatial variation did exist between …

Serological Evidence For The Co-Circulation Of Two Lineages Of Influenza D Virus In Equine Populations Of The Midwest United States, Hunter Theodore Nedland

Electronic Theses and Dissertations

Influenza D virus (IDV) is a newly described lineage of the Orthomyxoviridae virus family that was first isolated from diseased swine in 2011 and has subsequently been detected in cattle around the world in 2014. In addition, serological evidence for IDV infection in humans has been recently established. Despite all the progress, the full range of susceptible hosts for this novel virus has yet to be determined, but includes swine, bovine, small ruminants and human. This study was designed to determine if equine is a possible host to this newly emerging influenza virus. 364 equine serum samples were collected in …

The Role Of Neurokinin Receptors And Satellite Glial Cells In Herpes Simplex Virus 1 Latency, Andrew Jerome

Wayne State University Dissertations

The ability of herpes simplex virus 1 (HSV-1) to establish a lifelong infection in neurons of the trigeminal ganglion (TG) make it a constant public health threat. Viral reactivation from its latent state is currently the leading cause of viral induced blindness in the United State, as well as the leading cause of herpes simplex encephalitis. Unfortunately, how the virus is able to both establish and maintain its latent state in the TG is not well understood. The purpose of this work was to better understand how neuropeptide signaling through neurokinin receptors, as well as how satellite glial cells (SGCs) …

Evaluation Of A Microsphere-Based Immunoassay (Mia) In Measuring Diagnostic And Prognostic Markers Of Dengue Virus Infection, Jason H. Ambrose

USF Tampa Graduate Theses and Dissertations

Infections with dengue viruses (DENV) constitute both a global problem as well as locally in Florida. DENV comprise four distinct serotypes of single-stranded RNA viruses and belong to the family Flaviviridae. DENV are among the most medically important arboviruses in the world and cases may currently exceed 400 million per annum. Additionally, dengue established its first recorded endemic transmission cycle in the state of Florida in over a half century, first within the Florida Keys during 2009-10 followed by an unrelated outbreak in Martin County in 2013. The clinical profile of DENV infections ranges from a mild febrile illness …

Evasion Of Host Innate Immunity By Emerging Viruses: Antagonizing Host Rig-I Pathways, Maureen Ferran, Gary Skuse

Articles

Viruses confront a seemingly dichotomous relationship with their host cells. They must overcome host defenses in order to complete their infectious cycles and generate new viruses yet the host must remain healthy and hospitable for that to take place. Shortly after infection, the RIGI-like receptors (RLRs) within the cytoplasm of the infected cell recognize foreign motifs present in the pathogen. The host responds by activating a signaling pathway that leads to activation of cellular transcription factors, including the NF-κB and interferon regulatory factor 3 (IRF3), that are necessary for induction of the type 1 interferon genes. Many viruses subdue components …

Secreted Ns1 Aids In Dengue Virus Entry By Binding Heparan Sulfate, Morgan E. Schafer, Michael Dibiasio-White, Richard J. Kuhn

The Summer Undergraduate Research Fellowship (SURF) Symposium

A large portion of the world’s population lives in an area where they are at risk of contracting Dengue Virus (DENV). While infection with DENV can result in a wide range of clinical manifestations, from flu-like symptoms to hemorrhagic shock, vascular leakage, and even death, no treatments currently exist. Previous studies have shown that higher levels of viral non-structural protein 1 (NS1) in the blood of infected patients correlate with more severe disease. NS1 has been shown to play many roles in the viral lifecycle, but the mechanisms by which NS1 executes these functions are unknown. Preliminary data from our …

Osteopontin Facilitates West Nile Virus Neuroinvasion Via Neutrophil “Trojan Horse” Transport, Amber M. Paul, Dhiraj Acharya, Laurel Duty, E. Ashley Thompson, Linda Le, Dobrivoje S. Stokic, A. Arturo Leis, Fengwei Bai

Publications

West Nile virus (WNV) can cause severe human neurological diseases including encephalitis and meningitis. The mechanisms by which WNV enters the central nervous system (CNS) and host factors that are involved in WNV neuroinvasion are not completely understood. The proinflammatory chemokine osteopontin (OPN) is induced in multiple neuroinflammatory diseases and is responsible for leukocyte recruitment to sites of its expression. In this study, we found that WNV infection induced OPN expression in both human and mouse cells. Interestingly, WNV-infected OPN deficient (Opn−/−) mice exhibited a higher survival rate (70%) than wild type (WT) control mice (30%), suggesting OPN plays a …

Mutations In The Transmembrane Domain And Cytoplasmic Tail Of Hendra Virus Fusion Protein Disrupt Virus-Like-Particle Assembly, Nicolás P. Cifuentes-Muñoz, Weina Sun, Greeshma Ray, Phuong Tieu Schmitt, Stacy Webb, Kathleen Gibson, Rebecca Ellis Dutch, Anthony P. Schmitt

Molecular and Cellular Biochemistry Faculty Publications

Hendra virus (HeV) is a zoonotic paramyxovirus that causes deadly illness in horses and humans. An intriguing feature of HeV is the utilization of endosomal protease for activation of the viral fusion protein (F). Here we investigated how endosomal F trafficking affects HeV assembly. We found that the HeV matrix (M) and F proteins each induced particle release when they were expressed alone but that their coexpression led to coordinated assembly of virus-like particles (VLPs) that were morphologically and physically distinct from M-only or F-only VLPs. Mutations to the F protein transmembrane domain or cytoplasmic tail that disrupted endocytic trafficking …

Elucidating The Role Of Interleukin-17a In West Nile Virus Infection, Dhiraj Acharya

Dissertations

West Nile virus (WNV) is a neurotropic flavivirus of significant public health importance for which no therapeutics and vaccine are currently available. Interleukin-17A (IL-17A) is an inflammatory cytokine that regulates diverse immune functions, while its role is unclear in host’s immune response to WNV. Furthermore, CD8⁺ T cells are crucial components of immunity and play a vital role in recovery from WNV infection. Here, we report a previously unrecognized function of IL-17A in regulating CD8⁺ T cell cytotoxicity. We show that WNV induces the expression of IL-17A in both mouse splenocytes and human peripheral blood mononuclear cells cultured …

Tumor Necrosis Factor Alpha-Induced Recruitment Of Inflammatory Mononuclear Cells Leads To Inflammation And Altered Brain Development In Murine Cytomegalovirus-Infected Newborn Mice, Maria C. Seleme, Kate Kosmac, Stipan Jonjic, William J. Britt

Physical Therapy Faculty Publications

Congenital human cytomegalovirus (HCMV) infection is a significant cause of abnormal neurodevelopment and long-term neurological sequelae in infants and children. Resident cell populations of the developing brain have been suggested to be more susceptible to virus-induced cytopathology, a pathway thought to contribute to the clinical outcomes following intrauterine HCMV infection. However, recent findings in a newborn mouse model of the infection in the developing brain have indicated that elevated levels of proinflammatory mediators leading to mononuclear cell activation and recruitment could underlie the abnormal neurodevelopment. In this study, we demonstrate that treatment with tumor necrosis factor alpha (TNF-α)-neutralizing …

Genetic Interference And Receptor Biology Of Neglected Influenza Viruses, Runxia Liu

Electronic Theses and Dissertations

Influenza B virus (IBV) is an important pathogen that infects humans and causes seasonal influenza epidemics. By using next-generation sequencing (NGS) approach, we analyzed total mRNAs extracted from A549 cells infected with B/Brisbane/60/2008, and identified four defective genomes in IBV with two from the polymerase basic subunit 1 (PB1) segment and the other two from the matrix (M) segment. Each of them can potently inhibit the replication of IBV. One derived from PB1 segment was able to interfere modestly with influenza A virus (IAV) replication. The productions of the four defective RNAs are not dependent on the cell types. The …

Development And Characterization Of Histidine-Tagged Hpv16 L2 And Ms2-Arginine-Tagged Recombinant Proteins For Downstream Processes, Tahiyat Alothaim

Dissertations, Master's Theses and Master's Reports

Human papillomaviruses (HPVs) are the most common sexually transmitted infections. Persistent infection with HPV can lead to anogenital cancers including head and neck cancers. Three prophylactic vaccines have been approved to prevent against some types of HPV infection. However, the vaccines are HPV-type specific and protect mostly against the HPV types included in the vaccines. To offer broader protection against more HPV types, studies in the field are developing candidate vaccines targeting a conserved minor capsid protein, L2. Nevertheless, reagents for developing and assessing L2 vaccines are limited. For example, antibodies to assess the antigenicity of some L2 epitopes are …

The Neonatal Anti-Viral Response Fails To Control Measles Virus Spread In Neurons Despite Interferon-Gamma Expression And A Th1-Like Cytokine Profile, Priya Ganesan

Electronic Theses and Dissertations

Neonates are highly susceptible to infections in the central nervous system (CNS) and have a greater risk of viral infections and encephalopathies. Neurotropic viral infections can lead to blindness, hearing loss and neurological deficiencies such as cognitive impairment, epilepsy, and even death in the neonatal and pediatric populations. Viral infections also are hypothesized to indirectly contribute to neurodegenerative and neuropsychiatric diseases such as Schizophrenia and Parkinson’s disease later in life due to early neuronal damage or stress. Many diverse viruses are capable of invading the neonatal CNS including Borna Disease Virus, Coxsackievirus (CV), Herpes simplex viruses (HSV), and measles virus. …

Using Rainbow Trout Cell Lines As A Model For Understanding The Innate Anti-Fv3 Immune Response, Graeme Robert Jones Lisser

Theses and Dissertations (Comprehensive)

Ranavirus infections are on the rise and have been implicated in numerous species die-offs across the globe. Frog virus 3 (FV3) is the type-species of the genus, yet the immune mechanisms governing susceptibility remain poorly understood. Arguably the most important immune response to infection is the type I interferon (IFN) response. Type I IFNs trigger an “antiviral state” in host cells via the production of numerous interferon-stimulated genes (ISGs) that act to inhibit virus replication in various way, including the induction of apoptosis. Apoptosis is an important antiviral defense mechanism to limit virus replication within infected cells. This study employed …

Regulation Of Alpha-Herpesvirus Reactivation From Latency By Stress, Insun Kook

School of Veterinary and Biomedical Sciences: Dissertations, Theses, and Student Research

Bovine herpes virus 1 (BHV-1) and Herpes simplex virus 1 (HSV-1) are crucial etiological viral agent of clinical diseases. HSV-1 and BHV-1 establish latent infection in sensory neurons. Periodically, reactivation from latency occurs resulting in virus excretion and transmission. Stress increases corticosteroid levels and the incidence of HSV-1 and BHV-1 reactivation from latency. The synthetic corticosteroid, dexamethasone (DEX) mimics stress and induces BHV-1 and HSV-1 reactivation. However, molecular mechanisms by which corticosteroid mediates viral reactivation are not well understood. My dissertation has focused on elucidating events that induce BHV- 1 or HSV-1 reactivation during the early stages of stress-induced escape …

Interleukin-17a Promotes Cd8 T Cell Cytotoxicity To Facilitate West Nile Virus Clearance, Amber M. Paul, Dhiraj Acharya, Penghua Wang, Jianfeng Dai, David Gate

Publications

CD8 T cells are crucial components of immunity and play a vital role in recovery from West Nile virus (WNV) infection. Here, we identify a previously unrecognized function of interleukin-17A (IL-17A) in inducing cytotoxic-mediator gene expression and promoting CD8 T cell cytotoxicity against WNV infection in mice. We find that IL-17A-deficient (Il17a/) mice are more susceptible to WNV infection and develop a higher viral burden than wild-type (WT) mice. Interestingly, the CD8 T cells isolated from Il17a/ mice are less cytotoxic and express lower levels of cytotoxic-mediator genes, which can be restored by supplying recombinant IL-17A in vitro and in …

An Ultrasensitive Electrogenerated Chemiluminescence-Based Immunoassay For Specific Detection Of Zika Virus, Amber M. Paul, Dhiraj Acharya, Pradip Bastola, Linda Le, Estenfani Fernandez, Michael S. Diamond, Wujian Miao, Fengwei Bai

Publications

Zika virus (ZIKV) is a globally emerging mosquito-transmitted flavivirus that can cause severe fetal abnormalities, including microcephaly. As such, highly sensitive, specific, and cost-effective diagnostic methods are urgently needed. Here, we report a novel electrogenerated chemiluminescence (ECL)-based immunoassay for ultrasensitive and specific detection of ZIKV in human biological fluids. We loaded polystyrene beads (PSB) with a large number of ECL labels and conjugated them with anti-ZIKV monoclonal antibodies to generate anti-ZIKV-PSBs. These anti-ZIKV-PSBs efficiently captured ZIKV in solution forming ZIKV-anti-ZIKV-PSB complexes, which were subjected to measurement of ECL intensity after further magnetic beads separation. Our results show that the anti-ZIKV-PSBs …

Respiratory Syncytial Virus-Infected Mesenchymal Stem Cells Regulate Immunity Via Interferon-Beta And Indoleamine-2,3-Dioxygenase, Michael B. Cheung

USF Tampa Graduate Theses and Dissertations

Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory tract infection in young children worldwide, accounting for an estimated 33.8 million cases of respiratory disease, over 3 million of which require hospitalization, and between 66,000 and 199,000 deaths in this susceptible population. Additionally, severe RSV infection early in life is associated with an increased risk of wheeze and other airway disorders later in life. Despite this, there is currently no vaccine or economically reasonable prophylactic regimen to prevent infection. While disease is typically more severe in infancy RSV can infect throughout the lifespan repeatedly as the …

A Single Exercise Bout Enhances The Manufacture Of Viral-Specific T-Cells From Healthy Donors: Implications For Allogeneic Adoptive Transfer Immunotherapy, Guillaume Spielmann, Catherine Bollard, Hawley Kunz, Patrick J. Hanley, Richard J. Simpson

Pediatrics Faculty Publications

Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections remain a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). The adoptive transfer of donor-derived viral-specific cytotoxic T-cells (VSTs) is an effective treatment for controlling CMV and EBV infections after HSCT; however, new practical methods are required to augment the ex vivo manufacture of multi-VSTs from healthy donors. This study investigated the effects of a single exercise bout on the ex vivo manufacture of multi-VSTs. PBMCs isolated from healthy CMV/EBV seropositive participants before (PRE) and immediately after (POST) 30-minutes of cycling exercise were stimulated with CMV (pp65 and …

Characterization Of Induced Rnai Silencing Of Vaccinia Virus Essential Genes, Kewa Jiang

University Scholar Projects

Vaccinia virus (VACV) is a large double-stranded DNA virus and the prototypical member of the family Poxviridae and is most notable for its use as the vaccine that eradicated smallpox (variola virus). More recently, VACV has been used to develop recombinant vaccines and immunotherapies. However, many of these processes require VACV replication to be tightly controlled. RNA interference (RNAi) is a powerful tool for in vitro silencing of mRNAs that are complimentary to 19-21 base pairs (bp) of double-stranded RNA (dsRNA). This project outlines the design and preliminary analysis of two inducible RNAi silencing constructs targeting multiple VACV essential genes …

Stabilization Of Gp120 Outer Domain For Hiv-1-1 Vaccine Immunogen Design, Duoyi Hu

School of Veterinary and Biomedical Sciences: Dissertations, Theses, and Student Research

The sole envelope glycoprotein spike on the surface of Human Immunodeficiency Virus (HIV-1) is composed of two subunits: gp120 and gp41. The gp120 consists of three domains: the inner domain, outer domain and bridging sheet, to which the viral primary receptor CD4 binds and induces a conformational change in gp120 to expose the co-receptor binding site. Previous studies have found that the outer domain of gp120 is relatively more stable than the inner domain and bridging sheet. When superimposed, the co-crystal structures of CD4-gp120 complex and VRC01-gp120 complex revealed that the CD4-binding site (CD4-BS) antibody VRC01 actually mainly bound to …

Characterization Of Induced Rnai Silencing Of Vaccinia Virus Essential Genes, Kewa Jiang

Honors Scholar Theses

Vaccinia virus (VACV) is a large double-stranded DNA virus and the prototypical member of the family Poxviridae and is most notable for its use as the vaccine that eradicated smallpox (variola virus). More recently, VACV has been used to develop recombinant vaccines and immunotherapies. However, many of these processes require VACV replication to be tightly controlled. RNA interference (RNAi) is a powerful tool for in vitro silencing of mRNAs that are complementary to 19-21 base pairs (bp) of double-stranded RNA (dsRNA). This project outlines the design and preliminary analysis of two inducible RNAi silencing constructs targeting multiple VACV essential genes …

Identification And Characterization Of Ion Channel Activity Of The M2 Protein From Influenza Virus D (Dm2), Jianing Liu

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

Viral ion channels are membrane proteins of influenza viruses that play essential roles in the replication cycle, which enables them to be targeted by antiviral drugs. M2 of influenza type A virus, BM2 of influenza type B virus, and CM2 from influenza type C virus have been characterized as ion channel proteins and antiviral drug amantadine was developed to control influenza type A virus. However, few studies have been conducted to clarify the properties of the M2 protein (DM2) of influenza type D virus, a novel influenza virus genus identified in 2014. To identify the ion channel activity of DM2, …

Determining The Role Of Poly [Adp-Ribose] Polymerase 1 (Parp-1) In Retroviral Infection, Luis Valdes Rodriguez

Open Access Theses & Dissertations

Possible links between PARP-1 and HIV-1 have been previously reported but the role of this protein during viral infection has remained elusive. Based on the high evolutionary conservation of PARP-1, from Drosophila to humans, we have been able to counteract the difficulties related with the functional redundancy manifested in the PARP family by studying the influence of PARP-1 on the expression of an endogenous retrovirus using the chicken B lymphoblastoid cell line DT40, this cell line exhibits low PARP-1 functional redundancy and is viable after PARP-1 knockout. We have determined that the transcription level of the endogenous retrovirus RAV-1 is …

Phylogenetic Investigation Of Enteric Bovine Coronavirus In Ireland Reveals Partitioning Between European And Global Strains, Lynda Gunn, P. J. Collins, M. J. O'Connell, Helen O'Shea

Department of Biological Sciences Publications

Background

Bovine coronavirus is a primary cause of neonatal calf diarrhea worldwide, and is also associated with acute diarrhea in adult cattle during the winter season. There are no reports on molecular characterization of bovine coronavirus in Ireland, and little data exists apart from serological studies.

Findings

In this study, 11 neonatal (mean age 9 days) calf BCoV strains from the south of Ireland were collected over a one year period and characterized using molecular methods. The spike gene which encodes a protein involved in viral entry, infectivity and immune response shows the most variability amongst the isolates and was …

Loss Of Glycosaminoglycan Receptor Binding After Mosquito Cell Passage Reduces Chikungunya Virus Infectivity, Amber M. Paul, Dhiraj Acharya, John F. Anderson, Faqing Huang, Fengwei Bai

Publications

Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that can cause fever and chronic arthritis in humans. CHIKV that is generated in mosquito or mammalian cells differs in glycosylation patterns of viral proteins, which may affect its replication and virulence. Herein, we compare replication, pathogenicity, and receptor binding of CHIKV generated in Vero cells (mammal) or C6/36 cells (mosquito) through a single passage. We demonstrate that mosquito cell derived CHIKV (CHIKVmos) has slower replication than mammalian cell derived CHIKV (CHIKVvero), when tested in both human and murine cell lines. Consistent with this, CHIKVmos infection in both cell lines produce less cytopathic …

A Tail Of Two Phages: Genomic And Functional Analysis Of Listeria Monocytogenes Phages Vb_Lmos_188 And Vb_Lmos_293 Reveal The Receptor-Binding Proteins Involved In Host Specificity, Aidan Casey, Kieran Jordan, Horst Neve, Aidan Coffey, Olivia Mcauliffe

Department of Biological Sciences Publications

The physical characteristics of bacteriophages establish them as viable candidates for downstream development of pathogen detection assays and biocontrol measures. To utilize phages for such purposes, a detailed knowledge of their host interaction mechanisms is a prerequisite. There is currently a wealth of knowledge available concerning Gram-negative phage-host interaction, but little by comparison for Gram-positive phages and Listeria phages in particular. In this research, the lytic spectrum of two recently isolated Listeria monocytogenes phages (vB_LmoS_188 and vB_LmoS_293) was determined, and the genomic basis for their observed serotype 4b/4e host-specificity was investigated using comparative genomics. The late tail genes of these …