Biological Phenomena, Cell Phenomena, and Immunity Commons^™

Retinal Ganglion Cell Neuroprotection Induced By Neuropharmacological Agents In An In-Vivo Model Of Glaucoma, Quinn Ameel

Honors Theses

Recent discoveries from this lab have demonstrated that activation of alpha7 nicotinic acetylcholine receptors (α7 nAChRs) on retinal ganglion cells (RGCs) in the retina is linked to neuroprotection of RGCs that are typically lost in glaucoma-like conditions. Various chemical agents have been produced to increase overall neurotransmission of ACh from cholinergic neurons. DMP-543 is an agent that increases calcium release from cholinergic synaptic terminals. Donepezil is an acetylcholinesterase inhibitor that inhibits the breakdown of ACh in the synaptic cleft, prolonging ACh’s effect. In this study, the neuroprotective activity of these two agents was analyzed at the synapse between starburst amacrine …

The Role Of Nicotine, A7 Nicotinic Acetylcholine Receptors And Extracellular Matrix Remodeling In Pulmonary Fibrosis., Glenn Ward Vicary

Electronic Theses and Dissertations

The median survival for idiopathic pulmonary fibrosis (IPF) patients from diagnosis is a dismal 3 years. This condition is characterized by pulmonary fibroproliferation and excess production and disordered deposition of extracellular matrix (ECM) proteins resulting in obliteration of the original tissue architecture, loss of lung function and eventual death due to respiratory failure. The main hindrance to the development of effective treatments against pulmonary fibrosis is the late detection of its progression and is often of unknown cause. Tobacco smoke represents the most important environmental factor linked to the development of pulmonary fibrosis, with over 60% of IPF patients current …

A Novel Codon-Optimized Siv Gag-Pol Immunogen For Gene-Based Vaccination, Catherine M. Crosby, Eric A. Weaver, Reeti Khare, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

Simian immunodeficiency virus (SIV) is a robust pathogen used in non-human primates to model HIV vaccines. SIV encodes a number of potential vaccine targets. By far the largest and most conserved protein target in SIV is its gag-pol protein that bears many epitopes to drive multivalent immune T cell responses. While gag-pol is an attractive antigen, it is only translated after a frame shift between gag and pol with the effect that gag and pol are expressed at an approximate 10/1 ratio. The codon bias of native lentiviral genes are also mismatched with the abundance of tRNAs in mammalian cells …

Immune Monitoring In Recipients Of Combined Living Donor Kidney And Hematopoietic Stem/Facilitating Cell Transplants., Mark Dewayne Badder

Electronic Theses and Dissertations

Solid organ transplantation coupled with a hematopoietic stem cell transplant from the organ donor allows for the recipient to cease immunosuppressive therapy after transplant via a chimeric immune system. This beneficial effect of stem cell transplants is negatively affected by graft versus host disease (GVHD). Better understanding of the donor and recipient’s immune system is vital to mitigating graft versus host disease and induction of donor chimerism without GVHD. In this study, flow cytometry was used to characterize immune cells of the recipients’ before and up to eighteen months post transplantation. The recipients were categorized into their respective chimeric groups. …

Endosomal Trafficking As A Determinant Of Antifungal Tolerance In The Pathogenic Fungus Candida Albicans, Arturo Luis Luna

Theses and Dissertations (ETD)

Several important antifungal drugs inhibit the synthesis of ergosterol, a lipid that modulates the thickness, fluidity and permeability of fungal cell membranes. These include the azole antifungals, which block ergosterol biosynthesis by inhibiting lanosterol demethylase (Erg11p). The resulting depletion of cellular ergosterol and the accumulation of ‘toxic’ sterol intermediates are both thought to cause plasma membrane dysfunction and ultimately growth arrest. However, the effects of ergosterol depletion upon the function of intracellular membranes and organelles are not well described. The purpose of this study was to characterize the effects of azole treatment upon the integrity of the Candida albicans vacuole, …

The Nucleolar Protein Nucleophosmin Undergoes Liquid-Liquid Phase Separation With Arginine-Rich Nucleolar Proteins Through Weak, Multivalent Electrostatic Interactions, Jaclyn Alicia Cika

Theses and Dissertations (ETD)

Nucleoli are nuclear membrane-less organelles that are the sites for ribosome biogenesis and serve as sensors of cellular stress. Weak, multivalent protein-protein interactions and interactions between disordered, low complexity domains (LCDs) and rRNA have been shown to promote liquid-liquid phase separation (LLPS) in vitro, suggesting a basis for the liquid-like behavior of nucleoli. Nucleophosmin (NPM1), a multifunctional and highly abundant nucleolar protein, exhibits structural features associated with LLPS suggesting a role in nucleolar organization. Specifically, NPM1 forms a pentamer through its N-terminal oligomerization domain and can bind to rRNA through its C-terminal nucleic acid binding domain. Multiple acidic tracts throughout …

Seniors Welcome! Avoiding The Trap Of Age Limits In Health Research, Arshad Jahangir

Journal of Patient-Centered Research and Reviews

The guest editor introduces this specialty issue of the Journal of Patient-Centered Research and Reviews, which focuses on cardiovascular diseases in the elderly. The reality of an aging population has increased the need for better evidence-based medicine in older patients. However, randomized controlled trials frequently exclude such patients, especially those with comorbidities, from study. This practice ignores the fact that physiologic changes to the cardiovascular system caused by the aging process and aging-associated diseases create clinical dilemmas distinct from those in younger patients. Considering the rising costs of health care and growing incidence of cardiovascular disease, research efforts and …

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 …

Identification Of Early Gene Expression Changes In Primary Cultured Neurons Treated With Topoisomerase I Poisons., Sharyn L. Rossi, Casey J. Lumpkin, Ashlee W. Harris, Jennifer Holbrook, Cinsley Gentillon, Suzanne M. Mccahan, Wenlan Wang, Matthew E.R. Butchbach

Department of Pediatrics Faculty Papers

Topoisomerase 1 (TOP1) poisons like camptothecin (CPT) are currently used in cancer chemotherapy but these compounds can have damaging, off-target effects on neurons leading to cognitive, sensory and motor deficits. To understand the molecular basis for the enhanced sensitivity of neurons to CPT, we examined the effects of compounds that inhibit TOP1-CPT, actinomycin D (ActD) and β-lapachone (β-Lap)-on primary cultured rat motor (MN) and cortical (CN) neurons as well as fibroblasts. Neuronal cells expressed higher levels of Top1 mRNA than fibroblasts but transcript levels are reduced in all cell types after treatment with CPT. Microarray analysis was performed to identify …

Peroxiredoxin Catalysis At Atomic Resolution, Arden Perkins, Derek Parsonage, Kimberly J. Nelson, O. Maduka Ogba, Paul Ha-Yeon Cheong, Leslie B. Poole, P. Andrew Karplus

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Peroxiredoxins (Prxs) are ubiquitous cysteine-based peroxidases that guard cells against oxidative damage, are virulence factors for pathogens, and are involved in eukaryotic redox regulatory pathways. We have analyzed catalytically active crystals to capture atomic resolution snapshots of a PrxQ-subfamily enzyme (from Xanthomonas campestris) proceeding through thiolate, sulfenate, and sulfinate species. These analyses provide structures of unprecedented accuracy for seeding theoretical studies, and show novel conformational intermediates giving insight into the reaction pathway. Based on a highly non-standard geometry seen for the sulfenate intermediate, we infer that the sulfenate formation itself can strongly promote local unfolding of the active site to …

Mitochondrial Akt Regulation Of Hypoxic Tumor Reprogramming., Young Chan Chae, Valentina Vaira, M. Cecilia Caino, Hsin-Yao Tang, Jae Ho Seo, Andrew V. Kossenkov, Luisa Ottobrini, Cristina Martelli, Giovanni Lucignani, Irene Bertolini, Marco Locatelli, Kelly G. Bryant, Jagadish C. Ghosh, Sofia Lisanti, Bonsu Ku, Silvano Bosari, Lucia R. Languino, David W. Speicher, Dario C. Altieri

Department of Cancer Biology Faculty Papers

Hypoxia is a universal driver of aggressive tumor behavior, but the underlying mechanisms are not completely understood. Using a phosphoproteomics screen, we now show that active Akt accumulates in the mitochondria during hypoxia and phosphorylates pyruvate dehydrogenase kinase 1 (PDK1) on Thr346 to inactivate the pyruvate dehydrogenase complex. In turn, this pathway switches tumor metabolism toward glycolysis, antagonizes apoptosis and autophagy, dampens oxidative stress, and maintains tumor cell proliferation in the face of severe hypoxia. Mitochondrial Akt-PDK1 signaling correlates with unfavorable prognostic markers and shorter survival in glioma patients and may provide an "actionable" therapeutic target in cancer.

Mucosal Vaccination By Adenoviruses Displaying Reovirus Sigma 1, Eric A. Weaver, Zenaido T. Camacho, Matthew L. Hillestad, Catherine M. Crosby, Mallory A. Turner, Adam J. Guenzel, Hind J. Fadel, George T. Mercier, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

We previously developed adenovirus serotype 5 (Ad5) vectors displaying the sigma 1 protein from reovirus as mucosal vaccines. Ad5-sigma retargets to JAM-1 and sialic acid, but had 40-fold reduced gene delivery when compared to Ad5. While weaker at transduction, Ad5-sigma generated stronger T cell responses than Ad5 when used for mucosal immunization. New Ad5-fiber-sigma vectors were generated here by varying the number of fiber β-spiral shaft repeats (R) fused between fiber tail and the sigma. Ad5 virions encoding R3, R14, and R20 chimeras were rescued. Increasing chimera length led to their decreasing encapsidation of these proteins in the virions. Ad5-R3 …

Loss Of Exogenous Androgen Dependence By Prostate Tumor Cells Is Associated With Elevated Glucuronidation Potential, Brenna M. Zimmer, Michelle E. Howell, Qin Wei, Linlin Ma, Trevor Romsdahl, Eileen G. Loughman, Jennifer E. Markham, Javier Seravalli, Joseph J. Barycki, Melanie A. Simpson

Department of Biochemistry: Faculty Publications

Prostate epithelial cells control the potency and availability of androgen hormones in part by inactivation and elimination. UDP-glucose dehydrogenase (UGDH) catalyzes the NAD⁺-dependent oxidation of UDP-glucose to UDP-glucuronate, an essential precursor for androgen inactivation by the prostate glucuronidation enzymes UGT2B15 and UGT2B17. UGDH expression is androgen stimulated, which increases the production of UDP-glucuronate, and fuels UGT-catalyzed glucuronidation. In this study, we compared the glucuronidation potential and its impact on androgen-mediated gene expression in an isogenic LNCaP model for androgen dependent versus castration resistant prostate cancer. Despite significantly lower androgen-glucuronide output, LNCaP 81 castration resistant tumor cells expressed higher …

Theaflavin-3, 3'-Digallate Induces Apoptosis And G2 Cell Cycle Arrest Through The Akt/Mdm2/P53 Pathway In Cisplatin-Resistant Ovarian Cancer A2780/Cp70 Cells, Youying Tu, Eunhye Kim, Ying Gao, Gary O. Rankin, Bo Li, Yi Charlie Chen

Pharmacology, Physiology and Toxicology

Ovarian cancer is the most lethal gynecological cancer among women worldwide. Adverse side effects and acquired resistance to conventional platinum based chemotherapy are major impediments in ovarian cancer treatment, and drive the development of more selective anticancer drugs that target cancer-specific defects. In this study, theaflavin-3, 3'-digallate (TF3), the major theaflavin monomer in black tea, exhibited a potent growth inhibitory effect on the cisplatinresistant ovarian cancer A2780/CP70 cells (IC50, 23.81 μM), and was less cytotoxic to a normal ovarian IOSE‑364 cells (IC50, 59.58 μM) than to the cancer cells. Flow cytometry analysis indicated that TF3 induced preferential apoptosis and G2 …

Modulation Of Nitric Oxide Synthase I Transcription By Tau And Alpha-Synuclein And Its Relevance To Alzheimer's And Parkinson's Diseases, Taelor A. Weaver, Alexandra L. Deal

Senior Honors Projects, 2010-2019

Alzheimer's Disease (AD) and Parkinson's Disease (PD) are both progressive neurodegenerative disorders that affect millions of Americans and for which there are no cures. AD can significantly impair the ability to think, remember, communicate, and carry out daily activities, while PD can affect motor functions such as balance, coordination, and the ability to speak. Intracellular protein aggregation is a hallmark of both diseases, with AD being characterized by the build up of neurofibrillary tangles composed of misfolded tau protein and PD being characterized by Lewy bodies composed of alpha-synuclein. Both normal tau and alpha-synuclein can localize to the nucleus; however, …

Porphyromonas Gingivalis Gingipains Induce A Pro-Inflammatory Extracellular Microenvironment : The Role Of Par-2 And Fibronectin., Jeffrey S. Marschall

Electronic Theses and Dissertations

Periodontitis is a chronic inflammatory disease that is characterized by severe tissue destruction of the gingiva and other tooth supporting structures; if left untreated, tooth loss and disintegration of the alveolar bone occurs. This chronic inflammatory state has been linked to other systemic diseases such as cardiovascular disease, diabetes, rheumatoid arthritis, and Alzheimer’s disease. Porphyromonas gingivalis is the major pathogenic microbe in periodontitis. The main virulence factors of P. gingivalis are the Arg-aa and Lys-aa gingipains, which are proteolytic enzymes implicated in a plethora of activities that allow P. gingivalis to subvert the human immune system in the oral cavity …

Abin1 In The Pathogenesis Of Glomerulonephritis And The Novel Polocyte-Neutrophil Proinflammatory Axis., Erik Anderson Korte

Electronic Theses and Dissertations

Glomerulonephritis (GN) is the most common cause of end-stage renal disease worldwide and is characterized by deposition of immune complex, inflammation, proteinuria and podocyte damage. Immunosuppressive therapy is effective in less than 50% of patients, indicating that immunological activity is not the only relevant cause of kidney injury. While methods have been described for neutrophil-mediated immune activation, specific glomerular mechanisms for recruitment of neutrophils and development of GN have not been determined. Here I present a pathogenic mechanism for the development of GN involving a novel podocyte-neutrophil axis and reveal the importance of glomerular NF-κB inhibition by the ubiquitin binding …

Redesigning Gfp Reporter System For Utilization In Clostridium Difficile, Laura E. Fitzgerald

Biological Sciences Undergraduate Honors Theses

Clostridium difficile (C. difficile) is a gram-positive bacterium that comprises part of the healthy human gut microbiome. When it gains sufficient access to peptides, C. difficile flourishes and releases tissue-damaging toxins, which cause inflammation of the colon that can develop into a Clostridium difficile Infection (CDI).¹⁰ The Ivey Laboratory believes that the best tactic in preventing CDIs is stopping peptide ingestion, which theoretically could be accomplished by manipulating the oligopeptide permease (App) system.⁷ In order to verify that altering the App system would successfully impede peptide uptake, first the expression of the app Promoter Region ( …

Pten Signaling In Regulatory T Cells And Inflammatory Disease, Sharad Krishna Shrestha

Theses and Dissertations (ETD)

Regulatory T (Treg) cells suppress CD4+ T cell responses during homeostasis and inflammation to prevent autoimmunity and other immune disorders. Although the transcriptional and epigenetic programs impacting Treg cell function have been extensively studied, the signaling and metabolic pathways underlying Treg stability and function are not fully understood. In this study, we determined the role of the phosphatase PTEN in Treg cells. We found that specific depletion of PTEN in Treg cells results in excessive TH1 and T follicular helper cells (TFH) responses, associated with elevated germinal center (GC) B cells and spontaneous development of autoimmune and lymphoproliferative disease in …

Identification Of Potential Drug Targets In Cancer Signaling Pathways Using Stochastic Logical Models, Peican Zhu, Hamidreza Montazeri Aliabadi, Hasan Uludag, Jie Han

Pharmacy Faculty Articles and Research

The investigation of vulnerable components in a signaling pathway can contribute to development of drug therapy addressing aberrations in that pathway. Here, an original signaling pathway is derived from the published literature on breast cancer models. New stochastic logical models are then developed to analyze the vulnerability of the components in multiple signalling sub-pathways involved in this signaling cascade. The computational results are consistent with the experimental results, where the selected proteins were silenced using specific siRNAs and the viability of the cells were analyzed 72 hours after silencing. The genes elF4E and NFkB are found to have nearly no …

Design, Synthesis, And Evaluation Of Chitosan Conjugated Ggrgdsk Peptides As A Cancer Cell-Targeting Molecular Transporter, Naglaa Salem El-Sayed, Amir Nasrolahi Shirazi, Magda Goda El-Meligy, Ahmed Kamel El-Ziaty, Zenat A. Nagieb, Keykavous Parang, Rakesh Tiwari

Pharmacy Faculty Articles and Research

Targeting cancer cells using integrin receptor is one of the promising targeting strategies in drug delivery. In this study, we conjugated an integrin-binding ligand (GGRGDSK) peptide to chitosan oligosaccharide (COS) using (sulfo-SMCC) bifunctional linker affording COS-SMCC-GGRGDSK. The conjugated polymer was characterized by FT-IR, ¹H NMR, ¹³C NMR, and SEM. COS-SMCC-GGRGDSK did not show cytotoxicity up to a concentration of 1 mg/mL in the human leukemia cell line (CCRF-CEM). The conjugate was evaluated for its ability to enhance the cellular uptake of cell-impermeable cargoes (e.g., FAM and F′-G(pY)EEI phosphopeptide) in CCRF-CEM, and human ovarian carcinoma (SK-OV-3) cancer …

The Effects Of Allergies And Anaphylaxis On The Body And Mind: A Survey Of Opinions And Knowledge On These Disorders, Kathryn E. O'Brien

Honors Program: Student Scholarship & Creative Works

Despite common knowledge, allergies and anaphylaxis are considered disabilities. As such, these disorders affect the daily lives of those who have them, including one's mental health. In this paper, all the nuances of allergies and anaphylaxis will be discussed as the etiology and scientific aspects of allergies, anaphylaxis, and hypersensitivity are distinguished from one another. Furthermore, the findings are reported from two surveys; an assessment of how well educated and prepared teachers are for students with allergies and whether other students with food allergies have had similar experiences to the author's and those described in research by other studies concerning …

Utility And Origin Of Blood-Based Autoantibodies For Early Detection And Diagnosis Of Neurodegenerative Diseases, Cassandra Demarshall

Graduate School of Biomedical Sciences Theses and Dissertations

Autoantibodies are self-reactive antibodies that have been widely implicated as causal agents of autoimmune diseases. They are found in the blood of all human sera, regardless of age, gender, or the presence or absence of disease. While the underlying reason for their ubiquity remains unknown, it has been hypothesized that they participate in the clearance of blood-borne cell and tissue debris generated in both healthy and diseased individuals on a daily basis. Although much evidence supports this debris clearance role, recent studies also suggest a causal role for autoantibodies in disease. My thesis work has focused on this "cause and/or …

Lineage-Specific Differences In The Gp120 Inner Domain Layer 3 Of Human And Simian Immunodeficiency Viruses, Shilei Ding, Halima Medjahed, Jérémie Prévost, Mathieu Coutu, Shi-Hua Xiang, Andrés Finzi

Nebraska Center for Virology: Faculty Publications

Binding of HIV-1 and SIV gp120 exterior envelope glycoprotein to CD4 triggers conformational changes in gp120 that promote its interaction with one of the chemokine receptors, usually CCR5, ultimately leading to gp41-mediated virus-cell membrane fusion and entry. We previously described that topological Layers (Layer 1, Layer 2 and Layer 3) in the gp120 inner domain contribute to gp120-trimer association in the unliganded state but also help secure CD4 binding. Relative to Layer 1 of HIV-1 gp120, the SIVmac239 gp120 Layer 1 plays a more prominent role in maintaining gp120-trimer association but is minimally involved in promoting CD4 binding, which could …

Active Stiffening Of F-Actin Network Dominated By Structural Transition Of Actin Filaments Into Bundles, Shengmao Lin, Xinwei Han, Gary C.P. Tsui, David Hui, Linxia Gu

Department of Mechanical and Materials Engineering: Faculty Publications

Molecular motor regulated active contractile force is key for cells sensing and responding to their mechanical environment, which leads to characteristic structures and functions of cells. The F-actin network demonstrates a two-order of magnitude increase in its modulus due to contractility; however, the mechanism for this active stiffening remains unclear. Two widely acknowledged hypotheses are that active stiffening of F-actin network is caused by (1) the nonlinear force-extension behavior of cross-linkers, and (2) the loading mode being switched from bending to stretching dominated regime. Direct evidence supporting either theory is lacking. Here we examined these hypotheses and showed that a …

Expression Levels Of Virulence Genes In Group A Streptococci: A Response To Aerosolized Propylene Glycol, Michael S. Costello

Honors Undergraduate Theses

Electronic cigarette usage is becoming increasingly prevalent among school age children and young adults. A known bactericidal agent, propylene glycol, is often used as a carrier for nicotine, flavoring, and additional constituents of electronic cigarette juice. This study examined the relationship between propylene glycol and virulence gene expression in Streptococcus pyogenes, a respiratory tract pathogen commonly found in school-age individuals. A variety of virulence genes controlled by the three stand alone regulators mga, RofA, and Rgg/RopB were sampled in an effort to understand the pathway by which virulence is affected. The genes chosen encode C5a peptidase, fibronectin binding protein, hyaluronate …

Giant Chloroviruses: Five Easy Questions, James L. Van Etten, David Dunigan

Nebraska Center for Virology: Faculty Publications

Chloroviruses are large, icosahedral, dsDNA-containing viruses that replicate in certain unicellular, chlorella-like green algae [1,2]. They exist in freshwater throughout the world with titers as high as thousands of plaque-forming units (PFU) per ml of indigenous water although titers are typically 1–100 PFU/ml. Titers fluctuate during the year with the highest titers typically occurring in the spring and late fall. Known chlorovirus hosts, which are normally symbionts and are often referred to as zoochlorellae, are associated with either the protozoan Paramecium bursaria (Fig 1A), the coelenterate Hydra viridis, or the heliozoan Acanthocystis turfacea. Zoochlorellae are resistant to viruses …

Genetic Barrier To Direct Acting Antivirals In Hcv Sequences Deposited In The European Databank, Dimas Alexandre Kliemann, Cristiane Valle Tovo, Ana Beatriz Gorini Da Veiga, André Luiz Machado, John T. West

Nebraska Center for Virology: Faculty Publications

Background & Aims: Development of resistance results from mutations in the viral genome, and the presence of selective drug pressure leads to the emergence of a resistant virus population. The aim of this study was to analyze the impact of genetic variability on the genetic barrier to drug resistance to DAAs.

Methods: The genetic barrier was quantified based on the number and type of nucleotide mutations required to impart resistance, considering full-length HCV NS3, NS5A and NS5B regions segregated by genotype into subtypes 1a, 1b, 2a, 2b and 3a. This study analyzed 789 NS3 sequences, 708 sequences and 536 NS5B …

Kaposi’S Sarcoma-Associated Herpesvirus Reduces Cellular Myeloid Differentiation Primary-Response Gene 88 (Myd88) Expression Via Modulation Of Its Rna, Amy Lingel, Erica Ehlers, Qianli Wang, Mingxia Cao, Charles Wood, Rongtuan Lin, Luwen Zhang

Nebraska Center for Virology: Faculty Publications

Kaposi’s sarcoma (KS)-associated herpesvirus (KSHV) is a human gammaherpesvirus associated with several human malignancies. The replication and transcription activator (RTA) is necessary and sufficient for the switch from KSHV latency to lytic replication. Interleukin 1 (IL-1) is a major mediator for inflammation and plays an important role in both innate and adaptive immunity. Myeloid differentiation primary response gene 88 (MyD88) is an essential adaptor molecule for IL-1 as well as most Toll-like receptor signaling. In this study, we identified a novel mechanism by which KSHV interferes with host inflammation and immunity. KSHV RTA specifically reduces the steady-state protein levels of …

Nf45 And Nf90 Bind Hiv-1 Rna And Modulate Hiv Gene Expression, Yan Li, Michael Belshan

Nebraska Center for Virology: Faculty Publications

A previous proteomic screen in our laboratory identified nuclear factor 45 (NF45) and nuclear factor 90 (NF90) as potential cellular factors involved in human immunodeficiency virus type 1 (HIV-1) replication. Both are RNA binding proteins that regulate gene expression; and NF90 has been shown to regulate the expression of cyclin T1 which is required for Tat-dependent trans-activation of viral gene expression. In this study the roles of NF45 and NF90 in HIV replication were investigated through overexpression studies. Ectopic expression of either factor potentiated HIV infection, gene expression, and virus production. Deletion of the RNA binding domains of NF45 …