Immunology of Infectious Disease Commons^™

Development Of Novel Zika And Anthrax Viral Nanoparticle Vaccines, Elizabeth Henderson

KGI Theses and Dissertations

Vaccines protect against numerous infectious diseases and prevent millions of deaths annually, but there are still many infectious diseases for which no licensed vaccine exists. Developing a new vaccine requires balancing safety and efficacy, and viral nanoparticle (VNP) vaccines possess both of these characteristics. The work herein demonstrates how tobacco mosaic virus (TMV) nanoparticles can serve as a platform to create candidate vaccines for Zika virus (ZIKV) and anthrax. In the first study, a ZIKV-specific epitope was genetically fused to TMV to create a safe and inexpensive vaccine that proved highly immunogenic in mice and led to the discovery of …

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 …

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 …

Enhanced Production Of Pro-Il-1Βeta Contributes To Immunopathology During The Coinfection Of Influenza A Virus And Streptococcus Pneumoniae, Angeline E. Rodriguez

Graduate Theses/Dissertations

Viral bacterial coinfections are known to cause severe pneumonia, especially in the elderly and in pediatric patients. Antibiotics like β-Lactams kill the bacteria but fail to improve symptoms suggesting a faulty immune system may play an important role in the disease. Interleukin-1β (IL-1β) is an important immune signaling cytokine responsible for inflammation. It exists as an inactive precursor that can be activated by caspase-1 containing inflammasomes (multi-protein complex). Influenza A virus (IAV) and Streptococcus pneumoniae (S. pneumoniae) activate the inflammasome through the NOD-like receptor protein NLRP3 and/or AIM2. Previous reports in mice indicate that IL-1β levels are dramatically …

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 …

The Kinetics Of Type I Interferons During Influenza A Virus Infection, Margaret A. Myers

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Gender Differences In Virologic Response After Antiretroviral Therapy In Treatment-Naïve Hiv-Infected Individuals: Results From The 550 Clinic Hiv Cohort Study., Andrea Reyes-Vega, Alejandra Loban, Kavitha Srinivasan, Stephen P. Furmanek, Conner English, Mary Bishop, Cathy Spencer, Daniel Truelove, Julio A. Ramirez, Anupama Raghuram, Paula Peyrani

Faculty and Staff Scholarship

Background

Controversy still exists regarding gender differences in virologic response between treatment-na•ve HIV-infected individuals. The objective of this study was to evaluate gender difference in virologic and immunologic response to antiretroviral therapy in treatment-na•ve HIV-infected individuals. Methods

This was a retrospective, observational study of treatment-na•ve HIV-infected individuals managed at the 550 clinic who started antiretroviral therapy (ART) between January 1st, 2010 and December 31, 2015. Patients with available viral load and CD4 counts before and one year after initiating ART were included in this study. Virologic suppression was defined as < 48 HIV-1 RNA copies/mL, and mmunologic recovery was defined as a CD4 count increase of at least 150 cells/mm3. Dichotomous variables were reported in number and percentages and analyzed using Chi-squared tests and Fisher’s exact (whichever was appropriate). Continuous variables were reported as median and interquartile range (IQR) and analyzed using Wilcox rank-sum tests. Multivariate analyses performed were logistic regressions with adjustment for other covariates. P value <0.05 was considered statistically significant. R version 3.3.2 was used for the statistical analysis. Results

A total of 70 women and 90 men were included …

Modeling Hiv Dynamics Following 3bnc117 Antibody Infusion, Samantha Erwin

Biology and Medicine Through Mathematics Conference

No abstract provided.

A Novel Role For Osteopontin In Facilitating West Nile Virus Neuroinvasion, Amber M. Paul

Dissertations

West Nile virus (WNV) is a positive-sensed, single-stranded RNA flavivirus that can cause human neuroinvasive diseases, including encephalitis, meningitis, and flaccid paralysis. The mechanisms by which WNV enters the central nervous system and the host-factors that are involved in WNV-neuroinvasiveness are not completely understood. Osteopontin (OPN), a multifunctional glycoprotein, has been implicated as a bio-marker for a number of neuroinflammatory diseases. In particular, secreted (s)OPN has been implicated to participate in recruitment of polymorphonuclear neutrophils (PMN) to sites of its expression, while PMNs have been suggested to act as WNV reservoirs. Therefore, sOPN recruitment of PMNs may contribute to neuroinvasive …

A Comparative Analysis Of The West African Hemorrhagic Fevers Caused By The Lassa And Ebola Viruses, Emiene E. Amali-Adekwu

Selected Honors Theses

Lassa fever (LF) and Ebola Hemorrhagic Fever (EHF) are viral diseases endemic to West Africa.The etiological agent of Lassa fever is an enveloped virus from the Arenaviridae family and was first discovered in 1969 when two missionary nurses died of a mysterious illness in the town of Lassa in Borno state, Nigeria.1 This virus is animal-borne (zoonotic) and is carried by the animal vector Mastomys natalensis (multimammate rat). The Ebola virus is also zoonotic originating from fruit bats belonging to the Pteropodidae family.2 The first reported case of Ebola Virus Disease (EVD) was a principal who was believed to have …

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 …

Mathematical Models Of Hiv And Hpv Coinfection, Samantha Erwin, Meghna Verma, Vida Abedi, Raquel Hontecillas-Magarzo, Stefan Hoops, Josep Bassaganya-Riera, Stanca M. Ciupe

Biology and Medicine Through Mathematics Conference

No abstract provided.

Norovirus Infection And Acquired Immunity In 8 Countries: Results From The Mal-Ed Study, Furqan Kabir, Adil Kalam, Pascal Bessong Pascal Bessong, Zulfiqar Ahmed Bhutta, Anita K. M. Zaidi, (Mal-Ed) Network Investigators, Imran Ahmed, Didar Alam, Syed Asad Ali, Shahida Qureshi, Muneera Rasheed, Sajid Bashir Soofi, Ali Turab, Aisha Khizar Yousafzai

Department of Paediatrics and Child Health

Background: Norovirus is an important cause of childhood diarrhea. We present data from a longitudinal, multicountry study describing norovirus epidemiology during the first 2 years of life.
Methods: A birth cohort of 1457 children across 8 countries contributed 7077 diarrheal stools for norovirus testing. A subset of 199 children contributed additional asymptomatic samples (2307) and diarrheal stools (770), which were used to derive incidence rates and evaluate evidence for acquired immunity.
Results: Across sites, 89% of children experienced at least 1 norovirus infection before 24 months, and 22.7% of all diarrheal stools were norovirus positive. Severity of norovirus-positive diarrhea was …

The Impact Of Polio Eradication On Routine Immunization And Primary Health Care: A Mixed-Methods Study, Svea Closser, Kelly Cox, Thomas M. Parris, R Matthew Landis, Judith Justice, Ranjani Gopinath, Kenneth Maes, Hailom Banteyerga Amaha, Ismaila Zango Mohammed, Rashid Jooma

Section of Neurosurgery

Background: After 2 decades of focused efforts to eradicate polio, the impact of eradication activities on health systems continues to be controversial. This study evaluated the impact of polio eradication activities on routine immunization (RI) and primary healthcare (PHC).
Methods: Quantitative analysis assessed the effects of polio eradication campaigns on RI and maternal healthcare coverage. A systematic qualitative analysis in 7 countries in South Asia and sub-Saharan Africa assessed impacts of polio eradication activities on key health system functions, using data from interviews, participant observation, and document review.
Results: Our quantitative analysis did not find compelling evidence of widespread and …

Phages Of Non-Diary Lactococci: Isolation And Characterization Of Phi L47, A Phage Infecting The Grass Isolate Lactococcus Lactis Ssp Cremoris Dpc6860, Daniel Cavanagh, Caitríona M. Guinane, Horst Neve, Aidan Coffey, R. Paul Ross, Gerald F. Fitzgerald, Olivia Mcauliffe

Department of Biological Sciences Publications

Lactococci isolated from non-dairy sources have been found to possess enhanced metabolic activity when compared to dairy strains. These capabilities may be harnessed through the use of these strains as starter or adjunct cultures to produce more diverse flavor profiles in cheese and other dairy products. To understand the interactions between these organisms and the phages that infect them, a number of phages were isolated against lactococcal strains of non-dairy origin. One such phage, ΦL47, was isolated from a sewage sample using the grass isolate L. lactis ssp. cremoris DPC6860 as a host. Visualization of phage virions by transmission electron …

Bovine Herpesvirus 1 Productive Infection Stimulates Inflammosome Formation And Caspase 1 Activity, Jianlin Wang, Jeffrey Alexander, Matthew S. Wiebe, Clinton J. Jones

Nebraska Center for Virology: Faculty Publications

Bovine herpesvirus 1 (BoHV-1), a significant viral pathogen of cattle, causes inflammation in affected tissue during acute infection. Consequently, we tested whether productively infected bovine cells stimulate inflammasome formation. Expression of two components required for inflammasome formation, the DNA sensor IFI16 (gamma-interferon-inducible protein 16) and NLRP3 (NOD-like receptor family, pyrin domain containing 3), were induced in bovine kidney cells by eight hours after infection. IFI16 was detected in punctate granules localized to the cytoplasm and nucleus. During productive infection, more than ten times more cells were caspase 1 positive, which is activated following inflammasome formation. Two caspase 1 inhibitors had …

A Supramolecular Strategy To Assemble Multifunctional Viral Nanoparticles, Limin Chen, Xia Zhao, Yuan Lin, Yubin Huang, Qian Wang

Faculty Publications

Using a one-pot approach driven by the supramolecular interaction between β-cyclodextrin and adamantyl moieties, multifunctional viral nanoparticles can be facilely formulated for biomedical applications.

Neurosteroid-Mediated Regulation Of Brain Innate Immunity In Hiv/Aids: Dhea-S Suppresses Neurovirulence, Amber Paul, Ferdinand G. Maingat, Maria J. Polyak, Pornpun Vivithanaporn, Farshid Noorbakhsh, Samir Ahboucha, Glen B. Baker, Keir Pearson, Christopher Power

Publications

Neurosteroids are cholesterol-derived molecules synthesized within the brain, which exert trophic and protective actions. Infection by human and feline immunodeficiency viruses (HIV and FIV, respectively) causes neuroinflammation and neurodegeneration, leading to neurological deficits. Secretion of neuroinflammatory host and viral factors by glia and infiltrating leukocytes mediates the principal neuropathogenic mechanisms during, although the effect of neurosteroids on these processes is unknown. We investigated the interactions between neurosteroid mediated effects and lentivirus infection outcomes. Analyses of HIV-infected uninfected human brains disclosed a reduction in neurosteroid synthesis enzyme expression. Human neurons exposed to supernatants from HIV macrophages exhibited suppressed enzyme expression without …

Role Of Poly [Adp-Ribose] Polymerase 1 In Retroviral Infection, Vanessa E. Rodriguez ^, Manuel Llano *

COURI Symposium Abstracts, Spring 2012

No abstract provided.

Study Guide For United In Anger: A History Of Act Up, Matt Brim

Open Educational Resources

The United in Anger Study Guide facilitates classroom and activist engagement with Jim Hubbard’s 2012 documentary, United in Anger: A History of ACT UP. The Study Guide contains discussion sections, projects and exercises, and resources for further research about the activism of the New York chapter of ACT UP (AIDS Coalition to Unleash Power). The Study Guide is a free, interactive, multimedia resource for understanding the legacy of ACT UP, the film’s role in preserving that legacy, and its meaning for viewers' lives.

Premature Induction Of An Immunosuppressive Regulatory T Cell Response During Acute Simian Immunodeficiency Virus Infection, Jacob D. Estes, Qingsheng Li, Matthew R. Reynolds, Stephen W. Wietgrefe, Lijie Duan, Timothy Schacker, Louis J. Picker, David I. Watkins, Jeffrey D. Lifson, Cavan Reilly, John V. Carlis, Ashley T. Haase

Qingsheng Li Publications

Here we report the results of an investigation into the possibility that one mechanism responsible for the establishment of persistent human immunodeficiency virus infection is an early regulatory T (T_reg) cell response that blunts virus- specific responses. Using the simian immunodeficiency virus (SIV)–infected rhesus macaque model, we show that, indeed, viral replication and immune activation in lymphatic tissue drive a premature immunosuppressive response, with dramatic increases in the frequencies of CD4⁺CD25⁺FOXP3⁺ Treg cells, transforming growth factor–β1⁺ cells, interleukin–10+ cells, and indoleamine 2,3-dioxygenase+CD3⁺ cells.When we compared SIV infection with rhesus cytomegalovirus (RhCMV) …

Quantitative Image Analysis Of Simian Immunodeficiency Virus Replication In Macrophages Coinfected With Mycobacterium Avium Complex, Qingsheng Li, Keith G. Mansfield, Andrew Lackner, Ashley T. Haase

Qingsheng Li Publications

Mycobacterium avium is the most frequent cause of disseminated bacterial infection in patients with human immunodeficiency virus type 1 infection and in rhesus macaques with simian immunodeficiency virus (SIV) infection. This animal model of AIDS was used to test the hypothesis that this frequent association is the result of reciprocal enhancement of replication of both microorganisms. The replication of M. avium and SIV was analyzed in lymphatic tissues obtained from rhesus macaques experimentally inoculated with SIVmac who developed or remained free of overt M. avium infection. In situ hybridization, quantitative image analysis, and staining of M. avium and of macrophages …

Characterization Of An Antiviral Agent Based On Nonionic Surfactants And It's Effects On Human Dermal Fibroblasts, Ji Young Li

Biological Sciences Theses & Dissertations

The AIDS ·pandemic has directed various research endeavors towards finding an appropriate method for eliminating all potentially infectious material within bone allografts before implantation into a recipient. To that effect, Panavirocide was conceived by Medicine and Applied Science·s, Inc. This compound, in which three nonionic surfactants serve as the active agents, has been shown to inactivate HIV-1 particles within blood and blood products. Because Panavirocide has never been used with allografts, the purpose of the present research was to characterize the nonionic surfactants for the putative alteration of the formulation by determining the critical micelle concentration values and to determine …