Medical Pathology Commons^™

Characterization Of A Species E Adenovirus Vector As A Zika Virus Vaccine, Brianna L. Bullard, Brigette N. Corder, David N. Gordon, Theodore C. Pierson, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

The development of a safe and efficacious Zika virus (ZIKV) vaccine remains a global health priority. In our previous work, we developed an Adenovirus vectored ZIKV vaccine using a low-seroprevalent human Adenovirus type 4 (Ad4-prM-E) and compared it to an Ad5 vector (Ad5-prM-E). We found that vaccination with Ad4-prM-E leads to the development of a strong anti-ZIKV T-cell response without eliciting significant anti-ZIKV antibodies, while vaccination with Ad5-prM-E leads to the development of both anti-ZIKV antibody and T-cell responses in C57BL/6 mice. However, both vectors conferred protection against ZIKV infection in a lethal challenge model. Here we continued to characterize …

Oral Contraceptives As Possible Acl Injury Prevention Method, Haley Schweizer

Capstone Showcase

ABSTRACT

Introduction: Anterior Cruciate Ligament (ACL) injuries are an upsetting setback for many athletes that require a long and costly recovery process. The injury rates are four times greater in women than men. Preventative measures that help to prevent ACL injuries are limited to stretching and strengthening. Therefore, this review aims to investigate if oral contraceptive [I] usage provides a possible new avenue for prevention of ACL injury [O] in young female athletes (ages 18-30) [P] compared to those that do not take oral contraceptives [C].

Methods: A literature review was performed though PubMed, Google Scholar, SCOPUS Database, and ClinicalKey …

Analysis Of Student Perceptions Of Just-In-Time Teaching Pedagogy In Pharmd Microbiology And Immunology Courses, Charitha Madiraju, Eglis Tellez-Corrales, Henry Hua, Jozef Stec, Andromeda M. Nauli, Deborah M. Brown

Nebraska Center for Virology: Faculty Publications

Just-In-Time Teaching (JiTT) active learning pedagogy is utilized by various disciplines, but its value in a professional pharmacy curriculum has not yet been demonstrated. The purpose of our research study is to implement and evaluate JiTT in a Doctor of Pharmacy (PharmD) program. The impetus in implementing JiTT into a PharmD curriculum was to provide students with an out-of-classroom learning opportunity to enhance knowledge-based skills. The current study summarizes the implementation of JiTT in four distinct instances: two iterations of the required courses “Integrated Microbiology and Virology” (Fall 2016 and Fall 2017) and “Integrated Immunology” (Winter 2016–2017 and Winter 2017–2018). …

Cervico-Vaginal Inflammatory Cytokine And Chemokine Responses To Two Different Siv Immunogens, Nikki P.L. Toledo, Hongzhao Li, Robert W. Omange, Tamara G. Dacoba, Jose Crecente-Campo, Dane Schalk, Mohammad A. Kashem, Eva Rakasz, Nancy Schultz-Darken, Qingsheng Li, James B. Whitney, Maria J. Alonso, Francis A. Plummer, Ma Luo

Nebraska Center for Virology: Faculty Publications

Studies have shown that vaccine vectors and route of immunization can differentially activate different arms of the immune system. However, the effects of different HIV vaccine immunogens on mucosal inflammation have not yet been studied. Because mucosal sites are the primary route of HIV infection, we evaluated the cervico-vaginal inflammatory cytokine and chemokine levels of Mauritian cynomolgus macaques following immunization and boost using two different SIV vaccine immunogens. The PCS vaccine delivers 12 20-amino acid peptides overlapping the 12 protease cleavage sites, and the Gag/Env vaccine delivers the full Gag and full Env proteins of simian immunodeficiency virus. We showed …

Host Transcriptional Response To Persistent Infection With A Live-Attenuated Porcine Reproductive And Respiratory Syndrome Virus Strain, Jayeshbhai Chaudhari, Chia-Sin Liew, Aspen M. Workman, Jean-Jack Riethoven, David J. Steffen, Sarah Vitosh-Sillman, Hiep Vu

Nebraska Center for Virology: Faculty Publications

Both virulent and live-attenuated porcine reproductive and respiratory syndrome virus (PRRSV) strains can establish persistent infection in lymphoid tissues of pigs. To investigate the mechanisms of PRRSV persistence, we performed a transcriptional analysis of inguinal lymphoid tissue collected from pigs experimentally infected with an attenuated PRRSV strain at 46 days post infection. A total of 6404 differentially expressed genes (DEGs) were detected of which 3960 DEGs were upregulated and 2444 DEGs were downregulated. Specifically, genes involved in innate immune responses and chemokines and receptors associated with T-cell homing to lymphoid tissues were down regulated. As a result, homing of virus-specific …

Recommendations For Measuring Hiv Reservoir Size In Cure- Directed Clinical Trials., Luis J. Montaner, Qingsheng Li

Nebraska Center for Virology: Faculty Publications

Therapeutic strategies are being clinically tested either to eradicate the latent HIV reservoir or to achieve virologic control in the absence of antiretroviral therapy (ART). Attaining this goal will require a consensus on how best to measure the levels of persistently-infected cells with the potential to cause viral rebound upon ART cessation to assess the results of cure-directed strategies in vivo. Current measurements assess different aspects of the HIV provirus and its functionality, and produce divergent results. Here, we provide the collective insight and position from the BEAT-HIV Martin Delaney Collaboratory on which viral measurements to prioritize in HIV cure-directed …

Characterization Of A Speciese Adenovirus Vector As A Zika Virus Vaccine, Brianna L. Bullard, Brigette N. Corder, David N. Gordon, Theodore C. Pierson, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

The development of a safe and efficacious Zika virus (ZIKV) vaccine remains a global health priority. In our previous work, we developed an Adenovirus vectored ZIKV vaccine using a low-seroprevalent human Adenovirus type 4 (Ad4-prM-E) and compared it to an Ad5 vector (Ad5-prM-E). We found that vaccination with Ad4-prM-E leads to the development of a strong anti-ZIKV T-cell response without eliciting significant anti-ZIKV antibodies, while vaccination with Ad5-prM-E leads to the development of both anti-ZIKV antibody and T-cell responses in C57BL/6 mice. However, both vectors conferred protection against ZIKV infection in a lethal challenge model. Here we continued to characterize …

Non-Naturally Occurring Porcine Reproduction And Respiratory Syndrome Virus (Prrsv) And Methods Of Using, Hiep Lai Xuan Vu, Fernando Osorio, William W. Laegreid, Asit K. Pattnaik, Fangrui Ma

Nebraska Center for Virology: Faculty Publications

A non-naturally occuring porcine reproductive and respiratory syndrome virus (PRRSV) is provided herein, and methods of making and using the non-naturally occurring PRRSV also are provided.

Diversity Of Trna Clusters In The Chloroviruses, Garry A. Duncan, David D. Dunigan Ph. D., James L. Van Etten

Nebraska Center for Virology: Faculty Publications

Viruses rely on their host’s translation machinery for the synthesis of their own proteins. Problems belie viral translation when the host has a codon usage bias (CUB) that is different from an infecting virus due to differences in the GC content between the host and virus genomes. Here, we examine the hypothesis that chloroviruses adapted to host CUB by acquisition and selection of tRNAs that at least partially favor their own CUB. The genomes of 41 chloroviruses comprising three clades, each infecting a different algal host, have been sequenced, assembled and annotated. All 41 viruses not only encode tRNAs, but …

A Decade In Review: A Systematic Review Of Universal Influenza Vaccines In Clinical Trials During The 2010 Decade, Brigette N. Corder, Brianna L. Bullard, Gregory Poland, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

On average, there are 3–5 million severe cases of influenza virus infections globally each year. Seasonal influenza vaccines provide limited protection against divergent influenza strains. Therefore, the development of a universal influenza vaccine is a top priority for the NIH. Here, we report a comprehensive summary of all universal influenza vaccines that were tested in clinical trials during the 2010–2019 decade. Of the 1597 studies found, 69 eligible clinical trials, which investigated 27 vaccines, were included in this review. Information from each trial was compiled for vaccine target, vaccine platform, adjuvant inclusion, clinical trial phase, and results. As we look …

Evaluation Of Antibody Response Directed Against Porcine Reproductive And Respiratory Syndrome Virus Structural Proteins, Hung Q. Luong, Huong T.L. Lai, Hiep L.X. Vu

Nebraska Center for Virology: Faculty Publications

Luciferase-immunoprecipitation system (LIPS), a liquid phase immunoassay, was used to evaluate antibody responses directed against the structural proteins of PRRSV in pigs that were experimentally infected with virulent PRRSV strains. First, the viral N protein was used as a model antigen to validate the assay. The LIPS results were highly comparable to that of the commercial IDEXX PRRS X3 ELISA. Subsequently, the assay was applied to simultaneously measure antibody reactivity against all eight structural proteins of PRRSV. The highest immunoreactivities were detected against GP3, M, and N proteins while the lowest reactivity was detected against ORF5a protein. Comparative analysis of …

Species D Adenoviruses As Oncolytic Viral Vectors, Brianna L. Bullard, Brigette N. Corder, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

Oncolytic adenoviruses (Ad) have shown promising results in the therapeutic treatment of cancer. Ad type 5 (Ad5) is the most extensively utilized Ad type. However, several limitations exist to using Ad5 as an oncolytic virus, including high levels of anti-Ad5 neutralizing antibodies in the population, binding of the Ad5 hexon to blood coagulation factor X leading to liver sequestration and toxicity, and reduced expression of the primary receptor CAR on many tumors. Here, we use in vitro methods to explore the oncolytic potential of four alternative Ad types (Ad26, 28, 45, and 48) belonging to the species D Ad subgroup …

Hiv-1 Subtypes And Drug Resistance Mutations Among Female Sex Workers Varied In Different Cities And Regions Of The Democratic Republic Of Congo, Eun Hee Kwon, Godefroid M. A. Musema, Jessica Boelter, Sydney Townsend, Desire Tshala-Katumbay, Patrick K. Kayembe, John T. West, Charles Wood

Nebraska Center for Virology: Faculty Publications

Background Complex mosaic structures of HIV-1 were found in the Democratic Republic of Congo (DRC). Currently, there is limited information on the circulating HIV-1 strains, the distribution of these strains and antiretroviral (ART) resistant viruses in different regions of the country, and the HIV-1 strains harbored by the high-risk groups like female sex workers (FSW) reported to be the source of recombinant and ART resistant viruses.

Methods Dried Blood Spots (DBS), collected from 325 infected FSWs in ten cities from 2012 DRC HIV/STI Integrated Biological and Behavioral Surveillance Survey, were tested for HIV-1 genotypes and antiretroviral resistance mutations. Regional segregation …

How The Cervical Microbiota Contributes To Cervical Cancer Risk In Sub-Saharan Africa, Cameron Klein, Crispin Kahesa, Julius Mwalselage, John T. West, Charles Wood, Peter C. Angeletti

Nebraska Center for Virology: Faculty Publications

Despite ongoing efforts, sub-Saharan Africa faces a higher cervical cancer burden than anywhere else in the world. Besides HPV infection, definitive factors of cervical cancer are still unclear. Particular states of the cervicovaginal microbiota and viral infections are associated with increased cervical cancer risk. Notably, HIV infection, which is prevalent in sub-Saharan Africa, greatly increases risk of cervicovaginal dysbiosis and cervical cancer. To better understand and address cervical cancer in sub-Saharan Africa, a better knowledge of the regional cervicovaginal microbiome is required This review establishes current knowledge of HPV, HIV, cervicovaginal infections, and the cervicovaginal microbiota in sub-Saharan Africa. Because …

The Kaposi’S Sarcoma-Associated Herpesvirus (Kshv) Gh/Gl Complex Is The Predominant Neutralizing Antigenic Determinant In Kshv-Infected Individuals, Yasaman Mortazavi, Salum J. Lidenge, Tara Tran, John T. West, Charles Wood, For Yue Tso

Nebraska Center for Virology: Faculty Publications

Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiological agent of Kaposi’s sarcoma (KS), one of the most prevalent cancers of people living with HIV/AIDS in sub-Saharan Africa. The seroprevalence for KSHV is high in the region, and no prophylactic vaccine against the virus is available. In this study, we characterized the antigenic targets of KSHV-specific neutralizing antibodies (nAbs) in asymptomatic KSHV-infected individuals and KS patients with high nAbs titers. We quantified the extent to which various KSHV envelope glycoproteins (gB, ORF28, ORF68, gH, gL, gM, gN and gpK8.1) adsorbed/removed KSHV-specific nAbs from the plasma of infected individuals. Our study revealed that …

Mycoplasma Co-Infection Is Associated With Cervical Cancer Risk, Cameron Klein, Kandali Samwel, Crispin Kahesa, Julius Mwaiselage, John T. West, Charles Wood, Peter C. Angeletti

Nebraska Center for Virology: Faculty Publications

Tanzania faces one of the highest cervical cancer burdens in the world. Recent work has suggested that the bacterial family Mycoplasmataceae is associated with higher levels of human papillomavirus (HPV), human immunodeficiency virus (HIV), and pre-cancerous cervical lesions. Mycoplasmataceae infection in Tanzania is not well understood, especially when considering the differences between sexually transmitted species of Mycoplasmataceae. To establish the prevalence of common Mycoplasmataceae cervical infections and evaluate their relationship with risk factors for cervical cancer, 1160 Tanzanian women responded to an epidemiological questionnaire and were tested for HIV, HPV, cervical lesions, Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma spp., and Lactobacillus …

Incidence Of The Covid-19 In Iraq – Implications For Travellers, Maysaa Kadhim Al-Malkey, Maitham Ahmed Al-Sammak

Nebraska Center for Virology: Faculty Publications

The first emerged Coronavirus Disease 2019 (COVID-19) was in Wuhan, Hubei Province, China at the end of 2019, then spread to the rest of China [1], followed by the spread of the COVID-19 epidemics into the world caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) [2]. Many epidemiological assessments in different countries from Asia, Europe, and North America have been published [3]. Nevertheless, there are countries in the Middle East like Iraq, with a rapid increase in cases and a high number of deaths, with a lack of studies. It is worth noting that the Iraqi Foreign Ministry was …

Prevalence Of Kaposi's Sarcoma-Associated Herpesvirus And Transfusion-Transmissible Infections In Tanzanian Blood Donors, Salum J. Lidenge, Tara Tran, For Yue Tso, John R. Ngowi, Danielle M. Shea, Julius Mwaiselage, Charles Wood, John T. West

Nebraska Center for Virology: Faculty Publications

Objective: Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent for Kaposi's sarcoma (KS), one of the most common cancers in Tanzania. We have investigated KSHV prevalence and factors associated with KSHV infection in Tanzania.

Methods: This is a cross-sectional study of voluntary blood-donors from Dar es Salaam, Tanzania. Plasma was screened for KSHV, HIV-1, HBV, HCV and Treponema pallidum (syphilis). Associations between KSHV sero-status and risk factors were analyzed. Odds ratios (OR) and 95% confidence intervals (CI) are reported to evaluate risk factors of KSHV infection. All tests were 2-tailed, and P-values <0.05 were considered statistically significant.

Results: The overall KSHV seroprevalence was 56.9%. Significantly …

Perivascular Macrophages In The Neonatal Macaque Brain Undergo Massive Necroptosis After Simian Immunodeficiency Virus Infection, Diana G. Bohannon, Yueying Wang, Colin H. Reinhart, Julian B. Hattler, Jiangtao Luo, Hamid R. Okhravi, Jianshui Zhang, Qingsheng Li, Marcelo J. Kuroda, Woong-Ki Kim

Nebraska Center for Virology: Faculty Publications

We previously showed that rhesus macaques neonatally infected with simian immunodeficiency virus (SIV) do not develop SIV encephalitis (SIVE) and maintain low brain viral loads despite having similar plasma viral loads compared to SIV-infected adults. We hypothesize that differences in myeloid cell populations that are the known target of SIV and HIV in the brain contribute to the lack of neonatal susceptibility to lentivirus-induced encephalitis. Using immunohistochemistry and immunofluorescence microscopy, we examined the frontal cortices from uninfected and SIV-infected infant and adult macaques (n = 8/ea) as well as adults with SIVE (n = 4) to determine differences in myeloid …

Lack Of Cd8+ T-Cell Co-Localization With Kaposi’S Sarcoma- Associated Herpesvirus Infected Cells In Kaposi’S Sarcoma Tumors, Salum J. Lidenge, For Yue Tso, Owen Ngalamika, Jaydeep Kolape, John R. Ngowi, Julius Mwaiselage, Charles Wood, John T. West

Nebraska Center for Virology: Faculty Publications

Despite the close association between Kaposi’s sarcoma (KS) and immune dysfunction, it remains unclear whether tumor infiltrating immune cells (TIIC), by their absence, presence, or dysfunction, are mechanistically correlated with KS pathogenesis. Therefore, their potential capacity to serve as prognostic biomarkers of KS disease progression or control is unclear. Because epidemic-KS (EpKS) occurs with HIV-1 co-infection, it is particularly important to compare TIIC between EpKS and HIV-negative African endemic-KS (EnKS) to dissect the roles of HIV-1 and Kaposi Sarcoma-associated herpesvirus (KSHV) in KS pathogenesis. This cross-sectional study of 13 advanced KS (4 EnKS, 9 EpKS) patients and 3 healthy controls …

Epstein Barr Virus-Immortalizedｂlymphocytes Exacerbate Experimental Autoimmune Encephalomyelitis In Xenograft Mice, Pascal Polepole, Alison Bartenslager, Yutong Liu, Thomas M. Petro, Samodha C. Fernando, Luwen Zhang

Nebraska Center for Virology: Faculty Publications

Multiple sclerosis (MS) is the most common autoimmune disorder affecting the central nervous system. Epstein-Barr virus (EBV) is a causative agent for infectious mononucleosis (IM) that is associated with MS pathogenesis. However, the exact mechanism by which EBV, specifically in IM, increases the risk for MS remains unknown. EBV immortalizes primary B lymphocytes in vitro and causes excessive B lymphocyte proliferation in IM in vivo. In asymptomatic carriers, EBV-infected B lymphocytes still proliferate to certain degrees, the process of which is tightly controlled by the host immune systems. Experimental autoimmune encephalomyelitis (EAE) mimics key features of MS in humans and …

Genetic Diversity Of Potassium Ion Channel Proteins Encoded By Chloroviruses That Infect Chlorella Heliozoae, Carter Murry, Irina V. Agarkova, Jayadri S. Ghosh, Fiona C. Fitzgerald, Roger M. Carlson, Brigitte Hertel, Kerri Kukovetz, Oliver Rauh, Gerhard Thiel, James L. Van Etten

Nebraska Center for Virology: Faculty Publications

Chloroviruses are large, plaque-forming, dsDNA viruses that infect chlorella-like green algae that live in a symbiotic relationship with protists. Chloroviruses have genomes from 290 to 370 kb, and they encode as many as 400 proteins. One interesting feature of chloroviruses is that they encode a potassium ion (K+) channel protein named Kcv. The Kcv protein encoded by SAG chlorovirus ATCV-1 is one of the smallest known functional K+ channel proteins consisting of 82 amino acids. The KcvATCV-1 protein has similarities to the family of two transmembrane domain K+ channel proteins; it consists of two transmembrane -helixes with a pore region …

Viral And Immunological Analytes Are Poor Predictors Of The Clinical Treatment Response In Kaposi’S Sarcoma Patients, Salum J. Lidenge, For Yue Tso, Yasaman Mortazavi, John R. Ngowi, Danielle M. Shea, Julius Mwaiselage, Charles Wood, John T. West

Nebraska Center for Virology: Faculty Publications

Kaposi’s sarcoma-associated herpes virus (KSHV) is the etiologic agent for Kaposi’s sarcoma (KS). The prognostic utility of KSHV and HIV-1 (human immunodeficiency virus) viremia as well as immunological parameters in clinical management of participants with KS is unclear. The objective of this study was to investigate viral and immunological parameters as predictors of KS treatment responses in participants with KS from sub-Saharan Africa (SSA). Plasma KSHV-DNA, HIV-1 viral load, total anti-KSHV antibody, KSHV-neutralizing antibody (nAb), cytokine/chemokine levels, and T-cell differentiation subsets were quantified before and after KS treatment in 13 participants with KS and in 13 KSHV-infected asymptomatic control individuals. …

Manipulation Of Ar-V7 In Castrate Resistant Prostate Cancer, Sean Simpson

Capstone Showcase

Abstract

Introduction: Prostate cancer is the leading cancer affecting men of all races in the United States, and the second leading cause of cancer death in men. If caught early, many have had success in combating the disease, but if the cancer metastasizes, the 5-year survival rate drops to only 30%. Current treatment options heavily involve hormone therapy, radiation therapy, chemotherapy, and surgery. While these treatments can be effective for early stage prostate cancer, they can fall short in preventing the spread of the cancer to other parts of the body. This review analyzes a new potential way of preventing …

Analyzing The Effects Of Opioids On Cortical Pore Networks In Rabbit Tibiae And Femora, Kassidy Wilson

Williams Honors College, Honors Research Projects

The following project was approved by the Institutional Animal Care and Use Committee (IACUC) (Protocol number #18-11-12 ARC). This study was completed as a subset of Dr. Andronowski's overarching lab project. Femora and tibiae were procured from New Zealand White rabbits to study the prolonged effects of opioid use in bone remodeling. This specific project analyzed the effects of opioids on the pore networks and the pore orientation.

Law, Structural Racism, And The Covid-19 Pandemic, Ruqaiijah Yearby, Seema Mohapatra

All Faculty Scholarship

Racial and ethnic minorities have always been the most impacted by pandemics because of: disparities in exposure to the virus; disparities in susceptibility to contracting the virus; and disparities in treatment. This article explains how structural racism, the ways in which laws are used to advantage the majority and disadvantage racial and ethnic minorities, has caused these disparities. Specifically, this article focuses on how employment, housing, health care, and COVID-19 relief laws have been manipulated to disadvantage racial and ethnic minorities, making minorities more susceptible to COVID-19 infection and death. This article uses Blumenshine’s 2008 framework to outline how structural …

Functional Impact Of Angiotensinogen Specific Domains On Angiotensin Ii-Mediated Functions, Chia-Hua Wu

Theses and Dissertations--Pharmacology and Nutritional Sciences

Angiotensinogen (AGT) is the only substrate for all angiotensin peptides in the renin angiotensin system (RAS). Cleavage of AGT by renin is a rate-limiting step of angiotensin peptides productions in the RAS and regulates angiotensin peptides-associated pathophysiological functions. Only ten N-terminal residues are cleaved by renin and the functions of remaining part of AGT protein, which is called des(angiotensin I)AGT, remain unclear. Despite of pivotal roles of AGT in the RAS, studies related to how AGT is metabolized and how des(angiotensin I)AGT regulates AGT functions or AngII-mediated functions are limited.

Renin cleavage of AGT shows species specificity. It has been …

Tick-Borne Infections In New Hampshire: An Evaluation Of The Diagnostic Process In A Local Patient Population, Katherine Anderson

Honors Theses and Capstones

Overall, approximately 95 percent of reported cases of vector-borne disease were associated with ticks, making these the most medically important group of arthropods in the United States.¹ Despite the prevalence of tick-borne infections, the process for the diagnosis of this condition is not well studied. This study aims to analyze data from a pool of 100 patients who underwent testing for tick-borne disease in the same institution in Dover, New Hampshire during the most recent peak tick season of 2019. Information utilized in this study included: patient age, sex, location of testing (inpatient versus outpatient), diagnostic testing methods used …