Genetics and Genomics Commons^™

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 …

Aav-Crispr Gene Editing Is Negated By Pre-Existing Immunity To Cas9, Ang Li, Mark R Tanner, Ciaran M Lee, Ayrea E Hurley, Marco De Giorgi, Kelsey E Jarrett, Timothy H Davis, Alexandria M Doerfler, Gang Bao, Christine Beeton, William R Lagor

Faculty, Staff and Students Publications

Adeno-associated viral (AAV) vectors are a leading candidate for the delivery of CRISPR-Cas9 for therapeutic genome editing in vivo. However, AAV-based delivery involves persistent expression of the Cas9 nuclease, a bacterial protein. Recent studies indicate a high prevalence of neutralizing antibodies and T cells specific to the commonly used Cas9 orthologs from Streptococcus pyogenes (SpCas9) and Staphylococcus aureus (SaCas9) in humans. We tested in a mouse model whether pre-existing immunity to SaCas9 would pose a barrier to liver genome editing with AAV packaging CRISPR-Cas9. Although efficient genome editing occurred in mouse liver with pre-existing SaCas9 immunity, this was accompanied by …

Determining The Genetic Control Of Neural Tube Malformation Through Genetic Interactions With Idgf3, Elli N. Fox

Honors Projects

Genetic mutations disrupting human neural tube formation can lead to birth defects such as spina bifida and anencephaly. Defects can result in lack of neural tube closure in either the caudal (spina bifida) or cranial (anencephaly) regions. Little is known about the genes that cause these malformations. Researchers have been using the model organism Drosophila melanogaster in an attempt to determine genes responsible for neural tube malformations. Recently, an ortholog of human chitin-like protein, imaginal disc growth factor 3 (Idgf3), has been identified as important in the proper formation of Drosophila egg dorsal appendages. However, the molecular mechanism responsible for …

A Goldenbraid Cloning System For Synthetic Biology In Social Amoebae, Peter Kundert, Alejandro Sarrion-Perdigones, Yezabel Gonzalez, Mariko Katoh-Kurasawa, Shigenori Hirose, Peter Lehmann, Koen J T Venken, Gad Shaulsky

Faculty, Staff and Students Publications

GoldenBraid is a rapid, modular, and robust cloning system used to assemble and combine genetic elements. Dictyostelium amoebae represent an intriguing synthetic biological chassis with tractable applications in development, chemotaxis, bacteria-host interactions, and allorecognition. We present GoldenBraid as a synthetic biological framework for Dictyostelium, including a library of 250 DNA parts and assemblies and a proof-of-concept strain that illustrates cAMP-chemotaxis with four fluorescent reporters coded by one plasmid.

Integrating Mouse And Human Genetic Data To Move Beyond Gwas And Identify Causal Genes In Cholesterol Metabolism, Zhonggang Li, James A Votava, Gregory J M Zajac, Jenny N Nguyen, Fernanda B Leyva Jaimes, Sophia M Ly, Jacqueline A Brinkman, Marco De Giorgi, Sushma Kaul, Cara L Green, Samantha L St Clair, Sabrina L Belisle, Julia M Rios, David W Nelson, Mary G Sorci-Thomas, William R Lagor, Dudley W Lamming, Chi-Liang Eric Yen, Brian W Parks

Faculty, Staff and Students Publications

Identifying the causal gene(s) that connects genetic variation to a phenotype is a challenging problem in genome-wide association studies (GWASs). Here, we develop a systematic approach that integrates mouse liver co-expression networks with human lipid GWAS data to identify regulators of cholesterol and lipid metabolism. Through our approach, we identified 48 genes showing replication in mice and associated with plasma lipid traits in humans and six genes on the X chromosome. Among these 54 genes, 25 have no previously identified role in lipid metabolism. Based on functional studies and integration with additional human lipid GWAS datasets, we pinpoint Sestrin1 as …

Principles Of Rna Processing From Analysis Of Enhanced Clip Maps For 150 Rna Binding Proteins, Eric L Van Nostrand, Gabriel A Pratt, Brian A Yee, Emily C Wheeler, Steven M Blue, Jasmine Mueller, Samuel S Park, Keri E Garcia, Chelsea Gelboin-Burkhart, Thai B Nguyen, Ines Rabano, Rebecca Stanton, Balaji Sundararaman, Ruth Wang, Xiang-Dong Fu, Brenton R Graveley, Gene W Yeo

Faculty, Staff and Students Publications

BACKGROUND: A critical step in uncovering rules of RNA processing is to study the in vivo regulatory networks of RNA binding proteins (RBPs). Crosslinking and immunoprecipitation (CLIP) methods enable mapping RBP targets transcriptome-wide, but methodological differences present challenges to large-scale analysis across datasets. The development of enhanced CLIP (eCLIP) enabled the mapping of targets for 150 RBPs in K562 and HepG2, creating a unique resource of RBP interactomes profiled with a standardized methodology in the same cell types.

RESULTS: Our analysis of 223 eCLIP datasets reveals a range of binding modalities, including highly resolved positioning around splicing signals and mRNA …

De Novo Frameshift Variants In The Neuronal Splicing Factor Nova2 Result In A Common C-Terminal Extension And Cause A Severe Form Of Neurodevelopmental Disorder, Francesca Mattioli, Gaelle Hayot, Nathalie Drouot, Bertrand Isidor, Jérémie Courraud, Maria-Victoria Hinckelmann, Frederic Tran Mau-Them, Chantal Sellier, Alica Goldman, Aida Telegrafi, Alicia Boughton, Candace Gamble, Sebastien Moutton, Angélique Quartier, Nolwenn Jean, Paul Van Ness, Sarah Grotto, Sophie Nambot, Ganka Douglas, Yue Cindy Si, Jamel Chelly, Zohra Shad, Elisabeth Kaplan, Richard Dineen, Christelle Golzio, Nicolas Charlet-Berguerand, Jean-Louis Mandel, Amélie Piton

Faculty, Staff and Students Publications

The neuro-oncological ventral antigen 2 (NOVA2) protein is a major factor regulating neuron-specific alternative splicing (AS), previously associated with an acquired neurologic condition, the paraneoplastic opsoclonus-myoclonus ataxia (POMA). We report here six individuals with de novo frameshift variants in NOVA2 affected with a severe neurodevelopmental disorder characterized by intellectual disability (ID), motor and speech delay, autistic features, hypotonia, feeding difficulties, spasticity or ataxic gait, and abnormal brain MRI. The six variants lead to the same reading frame, adding a common proline rich C-terminal part instead of the last KH RNA binding domain. We detected 41 genes differentially spliced after NOVA2 …

Assay Development For Isolation And Characterization Of Anticancer Properties Of Marine Fungi, Kyra Ricci

Honors Theses

Metabolites from fungi have potential use in the drug discovery process and have been used in the past to develop therapeutic agents for human use. Initial characterization of potential therapeutic properties of fungi is thus an important first step in identifying novel therapeutic compounds. In the present study, marine fungi were isolated from Myrtle Beach and assayed for anticancer properties using the soft agar colony formation assay in a 3D in vitro cellular environment. Many species were isolated from environmental samples, displaying unique morphologies and growth patterns. To optimize the soft agar assay in a six-well cell culture plate for …

Elucidating The Regulon Of A Fur-Like Protein In Mycobacterium Avium Subsp. Paratuberculosis (Map), Fernanda Miyagaki Shoyama, Taveesak Janetanakit, John P. Bannantine, Raul G. Barletta, Srinand Sreevatsan

Nebraska Center for Virology: Faculty Publications

Intracellular iron concentration is tightly regulated to maintain cell viability. Iron plays important roles in electron transport, nucleic acid synthesis, and oxidative stress. A Mycobacterium avium subsp. paratuberculosis (MAP)-specific genomic island carries a putative metal transport operon that includes MAP3773c, which encodes a Fur-like protein. Although well characterized as a global regulator of iron homeostasis in multiple bacteria, the function of Fur (ferric uptake regulator) in MAP is unknown as this organism also carries IdeR (iron dependent regulator), a native iron regulatory protein specific to mycobacteria. Computational analysis using PRODORIC identified 23 different pathways involved in respiration, metabolism, and virulence …

The Sineb1 Element In The Long Non-Coding Rna Malat1 Is Necessary For Tdp-43 Proteostasis, Tuan M Nguyen, Elena B Kabotyanski, Lucas C Reineke, Jiaofang Shao, Feng Xiong, Joo-Hyung Lee, Julien Dubrulle, Hannah Johnson, Fabio Stossi, Phoebe S Tsoi, Kyoung-Jae Choi, Alexander G Ellis, Na Zhao, Jin Cao, Oluwatoyosi Adewunmi, Josephine C Ferreon, Allan Chris M Ferreon, Joel R Neilson, Michael A Mancini, Xi Chen, Jongchan Kim, Li Ma, Wenbo Li, Jeffrey M Rosen

Faculty, Staff and Students Publications

Transposable elements (TEs) comprise a large proportion of long non-coding RNAs (lncRNAs). Here, we employed CRISPR to delete a short interspersed nuclear element (SINE) in Malat1, a cancer-associated lncRNA, to investigate its significance in cellular physiology. We show that Malat1 with a SINE deletion forms diffuse nuclear speckles and is frequently translocated to the cytoplasm. SINE-deleted cells exhibit an activated unfolded protein response and PKR and markedly increased DNA damage and apoptosis caused by dysregulation of TDP-43 localization and formation of cytotoxic inclusions. TDP-43 binds stronger to Malat1 without the SINE and is likely 'hijacked' by cytoplasmic Malat1 to the …

Using Active Learning To Build A Foundation For Bioinformatics Training., Stacey E. Wahl Ph.D., Amy L. Olex Ms

Transforming Libraries for Graduate Students

As Health Sciences Libraries evolve, the support they offer graduate students has evolved to incorporate many aspects of the research life cycle. At Tompkins-McCaw Library for the Health Sciences, we have partnered with the Wright Center for Clinical and Translational Research to offer training workshops for graduate students who are interested in using bioinformatics to plan, analyze, or execute scientific experiments. We offer two series: 1) an 8-week, 1-hour per week seminar series providing a general overview of available techniques and 2) a week-long intensive, two hours per session, series on utilizing free databases from the National Center for Biotechnology …

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 …

Potential Use Of Biotherapeutic Bacteria To Target Colorectal Cancer-Associated Taxa, Gareth Lawrence, Maire Begley, Paul D. Cotter, Caitríona M. Guinane

Department of Biological Sciences Publications

The role of the gut microbiome in human health and disease is the focus of much attention. It has been widely agreed upon that our gut bacteria play a role in host immunity, nutrient absorption, digestion, metabolism, and other key drivers of health. Furthermore, certain microbial signatures and specific taxa have also been associated with the development of diseases, such as obesity; inflammatory bowel disease; and, indeed, colorectal cancer (CRC), which is the focus of this review. By extension, such taxa represent potential therapeutic targets. In particular, the emerging human pathogen Fusobacterium nucleatum represents an important agent in CRC development …

Frontotemporal Dementia Nonsense Mutation Of Progranulin Rescued By Aminoglycosides, Lisha Kuang, Kei Hashimoto, Eric J. Huang, Matthew S. Gentry, Haining Zhu

Molecular and Cellular Biochemistry Faculty Publications

Frontotemporal dementia (FTD) is an early onset dementia and is characterized by progressive atrophy of the frontal and/or temporal lobes. FTD is highly heritable with mutations in progranulin accounting for 5-26% of cases in different populations. Progranulin is involved in endocytosis, secretion and lysosomal processes, but its function under physiological and pathological conditions remains to be defined. Many FTD-causing nonsense progranulin mutations contain a premature termination codon (PTC), thus progranulin haploinsufficiency has been proposed as a major disease mechanism. Currently, there is no effective FTD treatment or therapy.

Aminoglycosides are a class of antibiotics that possess a less known function …

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 …

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 …

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 …

Machine Learning Prediction Of Glioblastoma Patient One-Year Survival, Andrew Du '20, Warren Mcgee, Jane Y. Wu

Student Publications & Research

Glioblastoma (GBM) is a grade IV astrocytoma formed primarily from cancerous astrocytes and sustained by intense angiogenesis. GBM often causes non-specific symptoms, creating difficulty for diagnosis. This study aimed to utilize machine learning techniques to provide an accurate one-year survival prognosis for GBM patients using clinical and genomic data from the Chinese Glioma Genome Atlas. Logistic regression (LR), support vector machines (SVM), random forest (RF), and ensemble models were used to identify and select predictors for GBM survival and to classify patients into those with an overall survival (OS) of less than one year and one year or greater. With …

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). …

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 …

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 …

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 …

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 …

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. …

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 …

Aging Induces B Cell Defects And Decreased Antibody Responses To Influenza Infection And Vaccination, Daniela Frasca, Bonnie B. Blomberg

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Background: Aging is characterized by a progressive decline in the capacity of the immune system to fight influenza virus infection and to respond to vaccination. Among the several factors involved, in addition to increased frailty and high-risk conditions, the age-associated decrease in cellular and humoral immune responses plays a relevant role. This is in large part due to inflammaging, the chronic low-grade inflammatory status of the elderly, associated with intrinsic inflammation of the immune cells and decreased immune function.

Results: Aging is usually associated with reduced influenza virus-specific and influenza vaccine-specific antibody responses but some elderly individuals with higher pre-exposure …

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 …

Combination Of Investigational Cell-Based Therapy And Deep Brain Stimulation To Alter The Progression Of Parkinson’S Disease, Nader El Seblani

Theses and Dissertations--Pharmacy

Parkinson’s disease (PD) is the second most common neurodegenerative disorder and the motor symptoms are caused by progressive loss of midbrain dopamine neurons. There is no current treatment that can slow or reverse PD. Our current “DBS-Plus” clinical trial (NCT02369003) features the implantation in vivo of autologous Schwann cells (SCs) derived from a patient’s sural nerve into the substantia nigra pars compacta (SNpc) in combination with Deep Brain Stimulation (DBS) therapy for treating patients with advanced PD.

The central hypothesis of our research is that transdifferentiated SCs within conditioned nerve tissue will deliver pro-regenerative factors to enhance the survival of …