Life Sciences Commons^™

Structural Characterization Of A Conserved, Calcium-Dependent Periplasmic Protease From Legionella Pneumophila, Debashree Chatterjee, Chelsea D. Boyd, George A. O'Toole, Holger Sondermann

Dartmouth Scholarship

The bacterial dinucleotide second messenger c-di-GMP has emerged as a central molecule in regulating bacterial behavior, including motility and biofilm formation. Proteins for the synthesis and degradation of c-di-GMP and effectors for its signal transmission are widely used in the bacterial domain. Previous work established the GGDEF-EAL domain-containing receptor LapD as a central switch in Pseudomonas fluorescens cell adhesion. LapD senses c-di-GMP inside the cytosol and relays this signal to the outside by the differential recruitment of the periplasmic protease LapG. Here we identify the core components of an orthologous system in Legionella pneumophila. Despite only moderate sequence conservation at …

Lineage-Specific Differences Between Human And Simian Immunodeficiency Virus Regulation Of Gp120 Trimer Association And Cd4 Binding, Andrés Finzi, Beatriz Pacheco, Shi-Hua Xiang, Marie Pancera, Alon Herschhorn, Liping Wang, Xing Zeng, Anik Desormeaux, Peter D. Kwong, Joseph Sodroski

Nebraska Center for Virology: Faculty Publications

Metastable conformations of the gp120 and gp41 envelope glycoproteins of human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) must be maintained in the unliganded state of the envelope glycoprotein trimer. Binding of gp120 to the primary receptor, CD4, triggers the transition to an open conformation of the trimer, promoting interaction with the CCR5 chemokine receptor and ultimately leading to gp41-mediated virus-cell membrane fusion and entry. Topological layers in the gp120 inner domain contribute to gp120-trimer association in the unliganded state and to CD4 binding. Here we describe similarities and differences between HIV-1 and SIVmac gp120. In both …

Subunit Organization Of The Membrane-Bound Hiv-1 Envelope Glycoprotein Trimer, Youdong Mao, Liping Wang, Christopher Gu, Alon Herschhorn, Shi-Hua Xiang, Hillel Haim, Xinzhen Yang, Joseph Sodroski

Nebraska Center for Virology: Faculty Publications

The trimeric human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) spike is a molecular machine that mediates virus entry into host cells and is the sole target for virus-neutralizing antibodies. The mature Env spike results from cleavage of a trimeric gp160 precursor into three gp120 and three gp41 subunits. Here we describe an ~11-Å cryo-EM structure of the trimeric HIV-1 Env precursor in its unliganded state. The three gp120 and three gp41 subunits form a cage-like structure with an interior void surrounding the trimer axis. Interprotomer contacts are limited to the gp41 transmembrane region, the torus-like gp41 ectodomain, and …

Comparative Analysis Of The Fusion Efficiency Elicited By The Envelope Glycoprotein V1–V5 Regions Derived From Human Immunodeficiency Virus Type 1 Transmitted Perinatally, Hongyan Guo, Levon Abrahamyan, Chang Liu, Mackenzie Waltke, Yunqi Geng, Qimin Chen, Charles Wood, Xiaohong Kong

Nebraska Center for Virology: Faculty Publications

Understanding the properties of viruses preferentially establishing infection during perinatal transmission of human immunodeficiency virus type 1 (HIV-1) is critical for the development of effective measures to prevent transmission. A previous study demonstrated that the newly transmitted viruses (in infants) of chronically infected mother–infant pairs (MIPs) were fitter in terms of growth, which was imparted by their envelope (Env) glycoprotein V1–V5 regions, than those in the corresponding chronically infected mothers. In order to investigate whether the higher fitness of transmitted viruses was conferred by their higher entry efficiency directed by the V1–V5 regions during perinatal transmission, the fusogenicity of Env …

Coxsackievirus B3 Infection Leads To The Generation Of Cardiac Myosin Heavy Chain-Α-Reactive Cd4 T Cells In A/J Mice, Arunakumar Gangaplara, Chandirasegaran Massilamany, Deborah M. Brown, Gustavo A. Delhon, Asit K. Pattnaik, Nora Chapman, Noel Rose, David J. Steffen, Jay Reddy

Jay Reddy Publications

Enteroviruses like coxsackievirus B3 (CVB3) are common suspects in myocarditis/dilated cardiomyopathy patients. Autoimmunity has been proposed as an underlying mechanism, but direct evidence of its role is lacking. To delineate autoimmune response in CVB3 myocarditis, we used IA^k dextramers for cardiac myosin heavy chain (Myhc)-α 334–352. We have demonstrated that myocarditis-susceptible A/J mice infected with CVB3 generate Myhc-α-reactive CD4 T cells and such a repertoire was absent in naïve mice as measured by proliferative response to Myhc-α 334–352 and IA^k dextramer staining. We also detected Myhc-α 334–352 dextramer⁺ cells in the hearts of CVB3-infected mice. The autoreactive …

Glycosyl-Phosphatidylinositol (Gpi)-Anchored Membrane Association Of The Porcine Reproductive And Respiratory Syndrome Virus Gp4 Glycoprotein And Its Co-Localization With Cd163 In Lipid Rafts, Yijun Du, Asit K. Pattnaik, Cheng Song, Dongwan Yoo, Gang Li

School of Veterinary and Biomedical Sciences: Faculty Publications

The porcine reproductive and respiratory syndrome virus (PRRSV) glycoprotein 4 (GP4) resembles a typical type I membrane protein in its structure but lacks a hydrophilic tail at the C-terminus, suggesting that GP4 may be a lipid-anchored membrane protein. Using the human decay-accelerating factor (DAF; CD55), a known glycosyl-phosphatidylinositol (GPI) lipid-anchored protein, chimeric constructs were made to substitute the GPI-anchor domain of DAF with the putative lipid-anchor domain of GP4, and their membrane association and lipase cleavage were determined in cells. The DAF-GP4 fusion protein was transported to the plasma membrane and was cleaved by phosphatidylinositol-specific phospholipase C (PI-PLC), indicating that …

Fusion Of A Fluorescent Protein To The Pul25 Minor Capsid Protein Of Pseudorabies Virus Allows Live-Cell Capsid Imaging With Negligible Impact On Infection, Kevin P. Bohannon, Patricia J. Sollars, Gary E. Pickard, Gregory A. Smith

School of Veterinary and Biomedical Sciences: Faculty Publications

In order to resolve the location and activity of submicroscopic viruses in living cells, viral proteins are often fused to fluorescent proteins (FPs) and visualized by microscopy. In this study, we describe the fusion of FPs to three proteins of pseudorabies virus (PRV) that allowed imaging of capsids in living cells. Included in this study are the first recombinant PRV strains expressing FP–pUL25 fusions based on a design applied to herpes simplex virus type 1 by Homa and colleagues. The properties of each reporter virus were compared in both in vitro and in vivo infection models. PRV strains expressing FP–pUL25 …

Antibody Responses To Lytic And Latent Human Herpesvirus 8 Antigens Among Hiv-Infected Patients In Central China, Tiejun Zhang, Na He, Yingying Ding, Qingwu Jiang, Charles Wood

Nebraska Center for Virology: Faculty Publications

Human herpesvirus 8 (HHV8) is an important opportunistic infection of HIV/AIDS. However, very little is known about antibody seropositivities to HHV8 lytic and latent antigens among HIVinfected patients in China. Therefore, a cross-sectional study was conducted to explore HHV8 serostatus among 316 HIV-infected patients in a rural area of central China. The antibody seropositivity to HHV8 ORF65 (lytic) and LANA (latent) antigens was 12.7% and 10.4%, respectively. Patients who were naïve to antiretroviral therapy (ART) were more likely to be seropositive for antibodies to ORF65 (OR: 3.79; 95% CI: 1.71–8.42) and LANA (OR: 3.77; 95% CI: 1.55–9.14) than patients receiving …

Heme Oxygenase-1 Regulates The Immune Response To Influenza Virus Infection And Vaccination In Aged Mice, Nathan W. Cummins, Eric A. Weaver, Shannon M. May, Anthony J. Croatt, Oded Foreman, Richard B. Kennedy, Gregory A. Polan, Michael A. Barry, Karl A. Nath, Andrew D. Badley

Nebraska Center for Virology: Faculty Publications

Underlying mechanisms of individual variation in severity of influenza infection and response to vaccination are poorly understood. We investigated the effect of reduced heme oxygenase-1 (HO-1) expression on vaccine response and outcome of influenza infection. HO-1-deficient and wild-type (WT) mice (kingdom, Animalia; phylum, Chordata; genus/species, Mus musculus) were infected with influenza virus A/PR/8/34 with or without prior vaccination with an adenoviral-based influenza vaccine. A genome-wide association study evaluated the expression of single-nucleotide polymorphisms (SNPs) in the HO-1 gene and the response to influenza vaccination in healthy humans. HO-1-deficient mice had decreased survival after influenza infection compared to WT mice (median …

Chloroviruses: Not Your Everyday Plant Virus, James L. Van Etten, David D. Dunigan

Nebraska Center for Virology: Faculty Publications

Viruses infecting higher plants are among the smallest viruses known and typically have four to ten protein-encoding genes. By contrast, many viruses that infect algae (classified in the virus family Phycodnaviridae) are among the largest viruses found to date and have up to 600 protein- encoding genes. This brief review focuses on one group of plaque-forming phycodnaviruses that infect unicellular chlorella-like green algae. The prototype chlorovirus PBCV-1 has more than 400 protein-encoding genes and 11 tRNA genes. About 40% of the PBCV-1 encoded proteins resemble proteins of known function including many that are completely unexpected for a virus. In many …

Molecular Genetic And Biochemical Characterization Of The Vaccinia Virus I3 Protein, The Replicative Single-Stranded Dna Binding Protein, Matthew D. Greseth, Kathleen A. Boyle, Matthew S. Bluma, Bethany Unger, Matthew S. Wiebe, Jamaria A. Soares-Martins, Nadi T. Wickramasekera, James Wahlberg, Paula Traktman

Nebraska Center for Virology: Faculty Publications

Vaccinia virus, the prototypic poxvirus, efficiently and faithfully replicates its approximately 200-kb DNA genome within the cytoplasm of infected cells. This intracellular localization dictates that vaccinia virus encodes most, if not all, of its own DNA replication machinery. Included in the repertoire of viral replication proteins is the I3 protein, which binds to single-stranded DNA (ssDNA) with great specificity and stability and has been presumed to be the replicative ssDNA binding protein (SSB). We substantiate here that I3 colocalizes with bromodeoxyuridine (BrdU)-labeled nascent viral genomes and that these genomes accumulate in cytoplasmic factories that are delimited by membranes derived from …

Copper–Zinc Superoxide Dismutase-Deficient Mice Show Increased Susceptibility To Experimental Autoimmune Encephalomyelitis Induced With Myelin Oligodendrocyte Glycoprotein 35–55, Chandirasegara Massilamany, Arunakumar Gangaplara, Heejeong Kim, Charlotte Standord, Govardhan Rathnaiah, David Steffen, Jaekwon Lee, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

In this report, we have addressed the role of copper–zinc superoxide dismutase (SOD1) deficiency in the mediation of central nervous system autoimmunity. We demonstrate that SOD1-deficient C57Bl/6 mice develop more severe autoimmune encephalomyelitis induced with myelin oligodendrocyte glycoprotein (MOG) 35–55, compared with wild type mice. This alteration in the disease phenotype was not due to aberrant expansion of MOG-specific T cells nor their ability to produce inflammatory cytokines; rather lymphocytes generated in SOD1-deficient mice were more prone to spontaneous cell death when compared with their wild type littermate controls. The data point to a role for SOD1 in the maintenance …

An Epidemiological Model Of Rift Valley Fever With Spatial Dynamics, Tianchan Niu, Holly D. Gaff, Yiannis E. Papelis, David M. Hartley

Biological Sciences Faculty Publications

As a category A agent in the Center for Disease Control bioterrorism list, Rift Valley fever (RVF) is considered a major threat to the United States (USA). Should the pathogen be intentionally or unintentionally introduced to the continental USA, there is tremendous potential for economic damages due to loss of livestock, trade restrictions, and subsequent food supply chain disruptions. We have incorporated the effects of space into a mathematical model of RVF in order to study the dynamics of the pathogen spread as affected by the movement of humans, livestock, and mosquitoes. The model accounts for the horizontal transmission of …

Attenuation Of Corneal Myofibroblast Development Through Nanoparticle-Mediated Soluble Transforming Growth Factor-Β Type Ii Receptor (Stgfβrii) Gene Transfer, Ajay Sharma, Jason T. Rodier, Ashish Tandon, Alexander M. Klibanov, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Purpose: To explore (i) the potential of polyethylenimine (PEI)-DNA nanoparticles as a vector for delivering genes into human corneal fibroblasts, and (ii) whether the nanoparticle-mediated soluble extracellular domain of the transforming growth factor–β type II receptor (sTGFβRII) gene therapy could be used to reduce myofibroblasts and fibrosis in the cornea using an in vitro model.

Methods: PEI-DNA nanoparticles were prepared at a nitrogen-to-phosphate ratio of 30 by mixing linear PEI and a plasmid encoding sTGFβRII conjugated to the fragment crystallizable (Fc) portion of human immunoglobulin. The PEI-DNA polyplex formation was confirmed through gel retardation assay. Human corneal fibroblasts (HCFs) were …

Vorinostat: A Potent Agent To Prevent And Treat Laser-Induced Corneal Haze, Ashish Tandon, Jonathan C. K. Tovey, Michael R. Waggoner, Ajay Sharma, John W. Cowden, Daniel J. Gibson, Yuanjing Liu, Gregory S. Schultz, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

PURPOSE—This study investigated the efficacy and safety of vorinostat, a deacetylase (HDAC) inhibitor, in the treatment of laser-induced corneal haze following photorefractive keratectomy (PRK) in rabbits in vivo and transforming growth factor beta 1 (TGFβ1) -induced corneal fibrosis in vitro.

METHODS—Corneal haze in rabbits was produced with −9.00 diopters (D) PRK. Fibrosis in cultured human and rabbit corneal fibroblasts was activated with TGFβ1. Vorinostat (25 μm) was topically applied once for 5 minutes on rabbit cornea immediately after PRK for in vivo studies. Vorinostat (0 to 25 μm) was given to human/rabbit corneal fibroblasts for 5 minutes or 48 …

Mobilizing Subdominant Hiv-Specific Ctls As A Novel Vaccine Strategy, Margaret Christina Costanzo

Open Access Theses & Dissertations

To overcome the extreme antigenic diversity of HIV, there is increasing interest in developing vaccines that target CD8 T cell responses to conserved regions of the viral proteome. Understanding the immunogenic potential of these domains is therefore critical for the success of this vaccine strategy. CD8 T cell responses to conserved domains restricted by the "neutral" and highly prevalent HLA-A2 allele have not been extensively characterized. Here we describe a novel essentially invariant 10-mer epitope in HIV Gag (p2414-23, RTLNAWVKVV (RV10)) in that it is expressed by the majority HIV isolates from all clades. Here we examined the character of …

Evaluation Of Protection Induced By Dna Vaccine Candidate Against Leishmania Mexicana In Balb/C Mice Model, Rosina Rodarte

Open Access Theses & Dissertations

Background and Significance. The leishmaniases are a diverse group of diseases with four major clinical manifestations: cutaneous, mucocutaneous, visceral, and diffuse. Approximately 21 Leishmania species and 30 sandfly vectors have been implicated in human leishmaniasis. Leishmaniasis is endemic in 88 countries, 72 are developing countries. Currently, 350 million people live in leishmaniasis-endemic areas around the world. The true incidence of the disease is not known. However, the estimated incidence for visceral leishmaniasis is 500,000 cases per year, and for cutaneous and mucocutaneous leishmaniasis 1.5-2 million cases per year. Visceral leishmaniasis causes 70,000 deaths each year. In the Americas region, …

Signals From Intraventricular Depth Electrodes Can Control A Brain-Computer Interface, Jerry J. Shih, Dean J. Krusienski

Electrical & Computer Engineering Faculty Publications

A Brain-Computer Interface (BCI) is a device that enables severely disabled people to communicate and interact with their environments using their brain waves. Most research investigating BCI in humans have used scalp-recorded electroencephalography (EEG). We have recently demonstrated that signals from intracranial electrocorticography (ECoG) and stereotactic depth electrodes (SDE) in the hippocampus can be used to control a BCI P300 Speller paradigm. We report a case in which stereotactic depth electrodes positioned in the ventricle were able to obtain viable signals for a BCI. Our results demonstrate that event-related potentials from intraventricular electrodes can be used to reliably control the …

Effective Non-Viral Delivery Of Sirna To Acute Myeloid Leukemia Cells With Lipid-Substituted Polyethylenimines, Breanne Landry

Pharmacy Faculty Articles and Research

Use of small interfering RNA (siRNA) is a promising approach for AML treatment as the siRNA molecule can be designed to specifically target proteins that contribute to aberrant cell proliferation in this disease. However, a clinical-relevant means of delivering siRNA molecules must be developed, as the cellular delivery of siRNA is problematic. Here, we report amphiphilic carriers combining a cationic polymer (2 kDa polyethyleneimine, PEI2) with lipophilic moieties to facilitate intracellular delivery of siRNA to AML cell lines. Complete binding of siRNA by the designed carriers was achieved at a polymer:siRNA ratio of ~0.5 and led to siRNA/polymer complexes of …

A Shared Gene Expression Signature In Mouse Models Of Ebv-Associated And Non-Ebv-Associated Burkitt Lymphoma, Kathryn T. Bieging, Kamonwan Fish, Subbarao Bondada, Richard Longnecker

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The link between EBV infection and Burkitt lymphoma (BL) is strong, but the mechanism underlying that link has been elusive. We have developed a mouse model for EBV-associated BL in which LMP2A, an EBV latency protein, and MYC are expressed in B cells. Our model has demonstrated the ability of LMP2A to accelerate tumor onset, increase spleen size, and bypass p53 inactivation. Here we describe the results of total gene expression analysis of tumor and pretumor B cells from our transgenic mouse model. Although we see many phenotypic differences and changes in gene expression in pretumor B cells, the transcriptional …

Map Kinases Couple Hindbrain-Derived Catecholamine Signals To Hypothalamic Adrenocortical Control Mechanisms During Glycemia-Related Challenges, Arshad Khan, Kimberly Kaminski, Graciela Sanchez-Watts, Todd Ponzio, J. Kuzmiski, Jaideep Bains, Alan Watts

Selected Works Temporary Series

No abstract provided.

Map Kinases Couple Hindbrain-Derived Catecholamine Signals To Hypothalamic Adrenocortical Control Mechanisms During Glycemia-Related Challenges, Khan, Kimberly Kaminski, Graciela Sanchez-Watts, Todd Ponzio, J. Kuzmiski, Jaideep Bains, Alan Watts

Departmental Papers (Biology)

No abstract provided.

Lessons From Chimpanzee-Based Research On Human Disease: The Implications Of Genetic Differences, Jarrod Bailey

Laboratory Experiments Collection

Assertions that the use of chimpanzees to investigate human diseases is valid scientifically are frequently based on a reported 98–99% genetic similarity between the species. Critical analyses of the relevance of chimpanzee studies to human biology, however, indicate that this genetic similarity does not result in sufficient physiological similarity for the chimpanzee to constitute a good model for research, and furthermore, that chimpanzee data do not translate well to progress in clinical practice for humans. Leading examples include the minimal citations of chimpanzee research that is relevant to human medicine, the highly different pathology of HIV/AIDS and hepatitis C virus …

Functional Genomics Reveals An Essential And Specific Role For Stat1 In Protection Of The Central Nervous System Following Herpes Simplex Virus Corneal Infection, Tracy J. Pasieka, Cristian Cilloniz, Victoria S. Carter, Pamela Rosato, Michael G. Katze, David A. Leib

Dartmouth Scholarship

Innate immune deficiencies result in a spectrum of severe clinical outcomes following infection. In particular, there is a strong association between loss of the signal transducer and activator of transcription (Stat) pathway, breach of the blood-brain barrier (BBB), and virus-induced neuropathology. The gene signatures that characterize resistance, disease, and mortality in the virus-infected nervous system have not been defined. Herpes simplex virus type 1 (HSV-1) is commonly associated with encephalitis in humans, and humans and mice lacking Stat1 display increased susceptibility to HSV central nervous system (CNS) infections. In this study, two HSV-1 strains were used, KOS (wild type [WT]), …

Cellular Poly(C) Binding Proteins 1 And 2 Interact With Porcine Reproductive And Respiratory Syndrome Virus Nonstructural Protein 1Β And Support Viral Replication, Lalit Beura, Phat X. Dinh, Fernando A. Osorio, Asit K. Pattnaik

School of Veterinary and Biomedical Sciences: Faculty Publications

Porcine reproductive and respiratory syndrome virus (PRRSV) infection of swine results in substantial economic losses to the swine industry worldwide. Identification of cellular factors involved in PRRSV life cycle not only will enable a better understanding of virus biology but also has the potential for the development of antiviral therapeutics. The PRRSV nonstructural protein 1 (nsp1) has been shown to be involved in at least two important functions in the infected hosts: (i) mediation of viral subgenomic (sg) mRNA transcription and (ii) suppression of the host’s innate immune response mechanisms. To further our understanding of the role of the viral …

Empathy-Based Conservation: An Interdisciplinary Approach To Conservation Policy And Decision-Making, Kaitlyn Delashmutt

Department of Environmental Studies: Undergraduate Student Theses

In the late 20^th century, neuroscientists in Italy discovered a neuron in the brain capable of mentally mimicking the emotions derived from the actions of others (Rizzolatti and Craighero, 2004). It is the process that makes your elbow ache when someone else knocks their elbow on the counter or the uncontrollable smile that creeps up when someone smiles at you. No questions asked, people intuitively sense what others are feeling. The old school of thought was that humans deduced through logic and reason the actions of others and interpreted the emotions through a rational process (Carew et al, 2008). …

The Role Of Receptor Tyrosine Kinase Axl In Pancreatic Ductal Adenocarcinoma And Its Regulation By Hematopoietic Progenitor Kinase 1, Xianzhou Song

Dissertations and Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDA) is one of the most aggressive malignancies with less than 5% of five year survival rate. New molecular markers and new therapeutic targets are urgently needed for patients with PDA. Oncogenic receptor tyrosine kinase Axl has been reported to be overexpressed in many types of human malignancies, including diffuse glioma, melanoma, osteosarcoma, and carcinomas of lung, colon, prostate, breast, ovary, esophagus, stomach, and kidney. However, the expression and functions of Axl in PDA are unclear. We hypothesized that Axl contributes to the development and progression of PDA. We examined Axl expression in 54 human PDA samples …

Contribution Of Ectodomain Mutations In Epidermal Growth Factor Receptor To Signaling In Glioblastoma Multiforme, Marta L. Rojas

Dissertations and Theses (Open Access)

CONTRIBUTION OF ECTODOMAIN MUTATIONS IN EPIDERMAL GROWTH FACTOR RECEPTOR TO SIGNALING IN GLIOBLASTOMA MULTIFORME

Publication No._________

Marta Rojas, M.S.

Supervisory Professor: Oliver Bögler, Ph.D.

The Cancer Genome Atlas (TCGA) has conducted a comprehensive analysis of a large tumor cohort and has cataloged genetic alterations involving primary sequence variations and copy number aberrations of genes involved in key signaling pathways in glioblastoma (GBM). This dataset revealed missense ectodomain point mutations in epidermal growth factor receptor (EGFR), but the biological and clinical significance of these mutations is not well defined in the context of gliomas.

In our study, we focused on understanding …

Modelling Β2ar Regulation, Sharat J. Vayttaden

Dissertations and Theses (Open Access)

The β2 adrenergic receptor (β2AR) regulates smooth muscle relaxation in the vasculature and airways. Long- and Short-acting β-agonists (LABAs/SABAs) are widely used in treatment of chronic obstructive pulmonary disorder (COPD) and asthma. Despite their widespread clinical use we do not understand well the dominant β2AR regulatory pathways that are stimulated during therapy and bring about tachyphylaxis, which is the loss of drug effects. Thus, an understanding of how the β2AR responds to various β-agonists is crucial to their rational use. Towards that end we have developed deterministic models that explore the mechanism of drug- induced β2AR regulation. These mathematical models …

Hiv-1 Tat Protein Promotes Neuronal Dysfunction Through Disruption Of Micrornas, J Robert Chang, Ruma Mukerjee, Asen Bagashev, Luis Del Valle, Tinatin Chabrashvili, Brian J. Hawkins, Johnny J. He, Bassel E. Sawaya

School of Medicine Faculty Publications

Over the last decade, small noncoding RNA molecules such as microRNAs (miRNAs) have emerged as critical regulators in the expression and function of eukaryotic genomes. It has been suggested that viral infections and neurological disease outcome may also be shaped by the influence of small RNAs. This has prompted us to suggest that HIV infection alters the endogenous miRNA expression patterns, thereby contributing to neuronal deregulation and AIDS dementia. Therefore, using primary cultures and neuronal cell lines, we examined the impact of a viral protein (HIV-1 Tat) on the expression of miRNAs due to its characteristic features such as release …