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Mitochondrial Mislocalization Underlies Abeta42-Induced Neuronal Dysfunction In A Drosophila Model Of Alzheimer's Disease., Kanae Iijima-Ando, Stephen A Hearn, Christopher Shenton, Anthony Gatt, Lijuan Zhao, Koichi Iijima

Department of Biochemistry and Molecular Biology Faculty Papers

The amyloid-beta 42 (Abeta42) is thought to play a central role in the pathogenesis of Alzheimer's disease (AD). However, the molecular mechanisms by which Abeta42 induces neuronal dysfunction and degeneration remain elusive. Mitochondrial dysfunctions are implicated in AD brains. Whether mitochondrial dysfunctions are merely a consequence of AD pathology, or are early seminal events in AD pathogenesis remains to be determined. Here, we show that Abeta42 induces mitochondrial mislocalization, which contributes to Abeta42-induced neuronal dysfunction in a transgenic Drosophila model. In the Abeta42 fly brain, mitochondria were reduced in axons and dendrites, and accumulated in the somata without severe mitochondrial …

Regulation Of Energy Stores And Feeding By Neuronal And Peripheral Creb Activity In Drosophila., Koichi Iijima, Lijuan Zhao, Christopher Shenton, Kanae Iijima-Ando

Department of Biochemistry and Molecular Biology Faculty Papers

The cAMP-responsive transcription factor CREB functions in adipose tissue and liver to regulate glycogen and lipid metabolism in mammals. While Drosophila has a homolog of mammalian CREB, dCREB2, its role in energy metabolism is not fully understood. Using tissue-specific expression of a dominant-negative form of CREB (DN-CREB), we have examined the effect of blocking CREB activity in neurons and in the fat body, the primary energy storage depot with functions of adipose tissue and the liver in flies, on energy balance, stress resistance and feeding behavior. We found that disruption of CREB function in neurons reduced glycogen and lipid stores …

Association Tests Of The Opioid Receptor System And Alcohol-Related Traits, Ryan Bennett

Theses and Dissertations

The opioid receptors and their endogenous ligands have long been implicated in a variety of traits including addiction, impulsive behaviors and substance dependence. Using phenotypic measurements collected from the IASPSAD, data from a latent class analysis and data from a SNP array and additional genotyping assays, association and regression tests were performed to determine the effects of common SNPs encoded in the genes of the opioid receptors and ligands on various traits relating to alcohol dependence. Although only one SNP can be reported as significant for substance dependence within alcoholics, there were a few results approaching significance that may offer …

Biological Diversity Of Prokaryotic Type Iv Secretion Systems, Cristina E Alvarez-Martinez, Peter J Christie

Faculty, Staff and Student Publications

Type IV secretion systems (T4SS) translocate DNA and protein substrates across prokaryotic cell envelopes generally by a mechanism requiring direct contact with a target cell. Three types of T4SS have been described: (i) conjugation systems, operationally defined as machines that translocate DNA substrates intercellularly by a contact-dependent process; (ii) effector translocator systems, functioning to deliver proteins or other macromolecules to eukaryotic target cells; and (iii) DNA release/uptake systems, which translocate DNA to or from the extracellular milieu. Studies of a few paradigmatic systems, notably the conjugation systems of plasmids F, R388, RP4, and pKM101 and the Agrobacterium tumefaciens VirB/VirD4 system, …

Dopamine-Stimulated Dephosphorylation Of Connexin 36 Mediates Aii Amacrine Cell Uncoupling, W Wade Kothmann, Stephen C Massey, John O'Brien

Faculty, Staff and Student Publications

Gap junction proteins form the substrate for electrical coupling between neurons. These electrical synapses are widespread in the CNS and serve a variety of important functions. In the retina, connexin 36 (Cx36) gap junctions couple AII amacrine cells and are a requisite component of the high-sensitivity rod photoreceptor pathway. AII amacrine cell coupling strength is dynamically regulated by background light intensity, and uncoupling is thought to be mediated by dopamine signaling via D(1)-like receptors. One proposed mechanism for this uncoupling involves dopamine-stimulated phosphorylation of Cx36 at regulatory sites, mediated by protein kinase A. Here we provide evidence against this hypothesis …

Effects Of Cannabinoid Receptor Interacting Protein (Crip1a) On Cannabinoid Receptor (Cb1) Function, Tricia Smith

Theses and Dissertations

EFFECTS OF CANNABINOID RECEPTOR INTERACTING PROTEIN (CRIP1a) ON CANNABINOID (CB1) RECEPTOR FUNCTION. By Tricia Hardt Smith, B.S., M.S. A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University Virginia Commonwealth University, 2009. Major Director: Dana E. Selley, Ph.D., Department of Pharmacology and Toxicology This dissertation examines modulation of cannabinoid CB1 receptor function by Cannabinoid Receptor Interacting Protein (CRIP1a), a novel protein that binds the C-terminus of CB1 receptors. In Human embryonic kidney cells expressing human CB1 receptors (hCB1-HEK) and hCB1-HEK cells stably co-expressing CRIP1a (hCB1-HEK-CRIP1a), quantitative immunoblotting revealed a CRIP1a/CB1 …

Detection Of Sub-Clinical Cwd Infection In Conventional Test-Negative Deer Long After Oral Exposure To Urine And Feces From Cwd+ Deer, Nicholas J. Haley, Candace K. Mathiason, Mark D. Zabel, Glenn C. Telling, Edward A Hoover

Microbiology, Immunology, and Molecular Genetics Faculty Publications

BACKGROUND: Chronic wasting disease (CWD) of cervids is a prion disease distinguished by high levels of transmissibility, wherein bodily fluids and excretions are thought to play an important role. Using cervid bioassay and established CWD detection methods, we have previously identified infectious prions in saliva and blood but not urine or feces of CWD+ donors. More recently, we identified very low concentrations of CWD prions in urine of deer by cervid PrP transgenic (Tg[CerPrP]) mouse bioassay and serial protein misfolding cyclic amplification (sPMCA). This finding led us to examine further our initial cervid bioassay experiments using sPMCA.

OBJECTIVES: We sought …

Evaluating Forensic Dna Evidence, Dan E. Krane

Biological Sciences Faculty Publications

No abstract provided.

Suppression Of Erbb-2 In Androgen-Independent Human Prostate Cancer Cells Enhances Cytotoxic Effect By Gemcitabine In An Androgen-Reduced Environment., Li Zhang, Jeffrey S. Davis, Stanislav Zelivianski, Fen-Fen Lin, Rachel Schutte, Thomas L. Davis, Ralph Hauke, Surinder K. Batra, Ming-Fong Lin

Journal Articles: Biochemistry & Molecular Biology

We examined the efficacy of combination treatments utilizing cytotoxic drugs plus inhibitors to members of the ErbB-ERK signal pathway in human prostate cancer (PCa) LNCaP C-81 cells. Under an androgen-reduced condition, 50nM gemcitabine caused about 40% growth suppression on C-81 cells. Simultaneous treatment of gemcitabine plus 10microM AG825 produced 60% suppression (p

Expression And Function Of Hypoxia Inducible Factor-1 Alpha In Human Melanoma Under Non-Hypoxic Conditions, Caroline N. Mills, Sandeep S. Joshi, Richard M. Niles

Biochemistry and Microbiology

Background

Hypoxia inducible factor-1 alpha (HIF-1α) protein is rapidly degraded under normoxic conditions. When oxygen tensions fall HIF-1α protein stabilizes and transactivates genes involved in adaptation to hypoxic conditions. We have examined the normoxic expression of HIF-1α RNA and protein in normal human melanocytes and a series of human melanoma cell lines isolated from radial growth phase (RGP), vertical growth phase (VGP) and metastatic (MET) melanomas.

Results

HIF-1α mRNA and protein was increased in RGP vs melanocytes, VGP vs RGP and MET vs VGP melanoma cell lines. We also detected expression of a HIF-1α mRNA splice variant that lacks part …

Nonhomologous End-Joining: Tdp1-Mediated Processing, Atm-Mediated Signaling, Amy Hawkins

Theses and Dissertations

This thesis investigates two separate features of nonhomologous end-joining (NHEJ) DNA repair: end processing, and DNA repair kinase signaling. DNA end processing was investigated in a mouse model of hereditary spinocerebellar ataxia with axonal neuropathy (SCAN1), a congenital neurodegenerative disease. SCAN1 is caused by a homozygous H493R mutation in the active site of tyrosyl-DNA phosphodiesterase (TDP1). To address how the H493R mutation elicits the specific pathologies of SCAN1 and to further elucidate the role of TDP1 in processing DNA end modifications, we generated a Tdp1 knockout mouse and characterized their behavior and specific repair deficiencies in extracts of embryonic fibroblasts …

Reactive Oxygen And Nitrogen Species Induce Protein And Dna Modifications Driving Arthrofibrosis Following Total Knee Arthroplasty., Theresa A Freeman, Javad Parvizi, Craig J Della Valle, Marla J Steinbeck

Department of Orthopaedic Surgery Faculty Papers

BACKGROUND: Arthrofibrosis, occurring in 3%-4% of patients following total knee arthroplasty (TKA), is a challenging condition for which there is no defined cause. The hypothesis for this study was that disregulated production of reactive oxygen species (ROS) and nitrogen species (RNS) mediates matrix protein and DNA modifications, which result in excessive fibroblastic proliferation.

RESULTS: We found increased numbers of macrophages and lymphocytes, along with elevated amounts of myeloperoxidase (MPO) in arthrofibrotic tissues when compared to control tissues. MPO expression, an enzyme that generates ROS/RNS, is usually limited to neutrophils and some macrophages, but was found by immunohistochemistry to be expressed …

Small-Molecule Screening Using A Human Primary Cell Model Of Hiv Latency Identifies Compounds That Reverse Latency Without Cellular Activation, Hung Chih Yang, Sifei Xing, Liang Shan, Karen O'Connell

University Faculty Publications and Creative Works

The development of highly active antiretroviral therapy (HAART) to treat individuals infected with HIV-1 has dramatically improved patient outcomes, but HAART still fails to cure the infection. The latent viral reservoir in resting CD4+ T cells is a major barrier to virus eradication. Elimination of this reservoir requires reactivation of the latent virus. However, strategies for reactivating HIV-1 through nonspecific T cell activation have clinically unacceptable toxicities. We describe here the development of what we believe to be a novel in vitro model of HIV-1 latency that we used to search for compounds that can reverse latency. Human primary CD4+ …

Timing Of Moderate Level Prenatal Alcohol Exposure Influences Gene Expression Of Sensory Processing Behavior In Rhesus Monkeys, Mary L. Schneider, Colleen F. Moore, Julie A. Larson, Christina S. Barr, Onofre T. Dejesus, Andrew D. Roberts

Physics and Astronomy Department Publications

Sensory processing disorder, characterized by over- or under-responsivity to non-noxious environmental stimuli, is a common but poorly understood disorder. We examined the role of prenatal alcohol exposure, serotonin transporter gene polymorphic region variation (rh5-HTTLPR), and striatal dopamine (DA) function on behavioral measures of sensory responsivity to repeated non-noxious sensory stimuli in macaque monkeys. Results indicated that early gestation alcohol exposure induced behavioral under-responsivity to environmental stimuli in monkeys carrying the short (s) rh5-HTTLPR allele compared to both early-exposed monkeys homozygous for the long (l) allele and monkeys from middle-to-late exposed pregnancies and controls, regardless of genotype. …

Human Uterine Natural Killer Cells But Not Blood Natural Killer Cells Inhibit Human Immunodeficiency Virus Type 1 Infection By Secretion Of Cxcl12, Teddy F. Mselle, Aexandra L. Howell, Mimi Ghosh, Charles R. Wira, Charles L. Sentman

Dartmouth Scholarship

Natural killer (NK) cells derived from the human female reproductive tract (FRT) are phenotypically and functionally distinct from those obtained from peripheral blood. Because the FRT is a primary site of human immunodeficiency virus type 1 (HIV-1) infection in women, we determined whether soluble factors secreted by uterine-derived NK (uNK) cells inhibit HIV-1 infection. Clonal populations of uNK cells were activated with interleukin-12 (IL-12) and IL-15, and conditioned media (CM) from these cultures evaluated for their ability to inhibit infection of cells by HIV-1_IIIB, HIV-1_NL4.3, and HIV-1_HC4 (X4-tropic) or HIV-1_BaL (R5-tropic) viruses. We found …

Levels Of The Secreted Vibrio Cholerae Attachment Factor Gbpa Are Modulated By Quorum-Sensing-Induced Proteolysis, Brooke A. Jude, Raquel M. Martinez, Karen Skorupski, Ronald K. Taylor

Dartmouth Scholarship

Vibrio cholerae is the etiologic agent of cholera in humans. Intestinal colonization occurs in a stepwise fashion, initiating with attachment to the small intestinal epithelium. This attachment is followed by expression of the toxin-coregulated pilus, microcolony formation, and cholera toxin (CT) production. We have recently characterized a secreted attachment factor, GlcNAc binding protein A (GbpA), which functions in attachment to environmental chitin sources as well as to intestinal substrates. Studies have been initiated to define the regulatory network involved in GbpA induction. At low cell density, GbpA was detected in the culture supernatant of all wild-type (WT) strains examined. In …

Development Of A Mouse Monoclonal Antibody Cocktail For Post-Exposure Rabies Prophylaxis In Humans., Thomas Müller, Bernhard Dietzschold, Hildegund Ertl, Anthony R Fooks, Conrad Freuling, Christine Fehlner-Gardiner, Jeannette Kliemt, Francois X Meslin, Charles E Rupprecht, Noël Tordo, Alexander I Wanderler, Marie Paule Kieny

Department of Microbiology and Immunology Faculty Papers

As the demand for rabies post-exposure prophylaxis (PEP) treatments has increased exponentially in recent years, the limited supply of human and equine rabies immunoglobulin (HRIG and ERIG) has failed to provide the required passive immune component in PEP in countries where canine rabies is endemic. Replacement of HRIG and ERIG with a potentially cheaper and efficacious alternative biological for treatment of rabies in humans, therefore, remains a high priority. In this study, we set out to assess a mouse monoclonal antibody (MoMAb) cocktail with the ultimate goal to develop a product at the lowest possible cost that can be used …

Killing Of Treponema Denticola By Mouse Peritoneal Macrophages, P. Gaibani, C. Vocale, S. Ambretti, F. Cavrini, Jacques Izard, L. Miragliotta, M. T. Pellegrino, V. Sambri

Department of Food Science and Technology: Faculty Publications

Treponema denticola has been identified as an important cause of periodontal disease and hypothesized to be involved in extra-oral infections. The objective of this study was to investigate the role of T. denticola cell length and motility during mouse peritoneal macrophages in vitro uptake. Macrophages, incubated under aerobic and anaerobic conditions, produced a similar amount of TNF-α when stimulated with Escherichia coli LPS. The uptake of FlgE- and CfpA-deficient mutants of T. denticola was significantly increased compared with the wild-type strain, due to cell size or lack of motility. Opsonization with specific antibodies considerably improved the treponemes’ uptake. …

Subconjunctivally Implantable Hydrogels With Degradable And Thermoresponsive Properties For Sustained Release Of Insulin To The Retina., Gauri P. Misra, Ravi S.J. Singh, Tomas S. Aleman, Samuel G. Jacobson, Thomas W. Gardner, Tao L. Lowe

College of Pharmacy Faculty Papers

The objective of this work is to develop subconjunctivally implantable, biodegradable hydrogels for sustained release of intact insulin to the retina to prevent and treat retinal neurovascular degeneration such as diabetic retinopathy. The hydrogels are synthesized by UV photopolymerization of N-isopropylacrylamide (NIPAAm) monomer and a dextran macromer containing multiple hydrolytically degradable oligolactate-(2-hydroxyetheyl methacrylate) units (Dex-lactateHEMA) in 25:75 (v:v) ethanol:water mixture solvent. Insulin is loaded into the hydrogels during the synthesis process with loading efficiency up to 98%. The hydrogels can release biologically active insulin in vitro for at least one week and the release kinetics can be modulated by varying …

Asymmetric Deactivation Of Hiv-1 Gp41 Following Fusion Inhibitor Binding., Kristen M Kahle, H Kirby Steger, Michael J Root

Department of Biochemistry and Molecular Biology Faculty Papers

Both equilibrium and nonequilibrium factors influence the efficacy of pharmaceutical agents that target intermediate states of biochemical reactions. We explored the intermediate state inhibition of gp41, part of the HIV-1 envelope glycoprotein complex (Env) that promotes viral entry through membrane fusion. This process involves a series of gp41 conformational changes coordinated by Env interactions with cellular CD4 and a chemokine receptor. In a kinetic window between CD4 binding and membrane fusion, the N- and C-terminal regions of the gp41 ectodomain become transiently susceptible to inhibitors that disrupt Env structural transitions. In this study, we sought to identify kinetic parameters that …

Accurate Molecular Classification Of Cancer Using Simple Rules., Xiaosheng Wang, Osamu Gotoh

Journal Articles: Genetics, Cell Biology & Anatomy

BACKGROUND: One intractable problem with using microarray data analysis for cancer classification is how to reduce the extremely high-dimensionality gene feature data to remove the effects of noise. Feature selection is often used to address this problem by selecting informative genes from among thousands or tens of thousands of genes. However, most of the existing methods of microarray-based cancer classification utilize too many genes to achieve accurate classification, which often hampers the interpretability of the models. For a better understanding of the classification results, it is desirable to develop simpler rule-based models with as few marker genes as possible.

METHODS: …

Mcl-1 Degradation During Hepatocyte Lipoapoptosis., Howard C. Masuoka, Justin L. Mott, Steven F. Bronk, Nathan W. Werneburg, Yuko Akazawa, Scott H. Kaufmann, Gregory J. Gores

Journal Articles: Biochemistry & Molecular Biology

The mechanisms of free fatty acid-induced lipoapoptosis are incompletely understood. Here we demonstrate that Mcl-1, an anti-apoptotic member of the Bcl-2 family, was rapidly degraded in hepatocytes in response to palmitate and stearate by a proteasome-dependent pathway. Overexpression of a ubiquitin-resistant Mcl-1 mutant in Huh-7 cells attenuated palmitate-mediated Mcl-1 loss and lipoapoptosis; conversely, short hairpin RNA-targeted knockdown of Mcl-1 sensitized these cells to lipoapoptosis. Palmitate-induced Mcl-1 degradation was attenuated by the novel protein kinase C (PKC) inhibitor rottlerin. Of the two human novel PKC isozymes, PKCdelta and PKC, only activation of PKC was observed by phospho-immunoblot analysis. As compared with …

Methods And Compositions For Vaccnation Of Animals With Prrsv Antigens With Improved Immunogenicity, Israrul H. Ansari, Fernando A. Osorio, Asit K. Pattnaik,

School of Veterinary and Biomedical Sciences: Faculty Publications

Pigs challenged with hypoglycosylated variants of Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) major surface protein GP5 exhibited increased production of PRRSV-neutralizing antibodies relative to the levels of neutralizing antibodies produced by pigs immunized with wild type (wt) or glycosylated GP5. This invention provides for methods of obtaining improved immune responses in pigs to PRRSV, compositions useful for obtaining the improved immune responses as well as isolated polynucleotides that encode hypoglycosylated variants of PRRSV major surface protein GP5.

The Effects Of Field-Of-View And Patient Size On Ct Numbers From Cone-Beam Computed Tomography., Katrina Y T Seet, Arvand Barghi, Slav Yartsev, Jacob Van Dyk

Oncology Publications

Cone-beam computed tomography (CBCT) is used for patient alignment before treatment and is ideal for use in adaptive radiotherapy to account for tumor shrinkage, organ deformation and weight loss. However, CBCT images are prone to artifacts such as streaking and cupping effects, reducing image quality and CT number accuracy. Our goal was to determine the optimum combination of cone-beam imaging options to increase the accuracy of image CT numbers. Several phantoms with and without inserts of known relative electron densities were imaged using the Varian on-board imaging system. It was found that CT numbers are most influenced by the selection …

Minimal Membrane Docking Requirements Revealed By Reconstitution Of Rab Gtpase-Dependent Membrane Fusion From Purified Components, Christopher Stroupe, Christopher M. Hickey, Joji Mima, Amy S. Burfeind, William Wickner

Dartmouth Scholarship

Rab GTPases and their effectors mediate docking, the initial contact of intracellular membranes preceding bilayer fusion. However, it has been unclear whether Rab proteins and effectors are sufficient for intermembrane interactions. We have recently reported reconstituted membrane fusion that requires yeast vacuolar SNAREs, lipids, and the homotypic fusion and vacuole protein sorting (HOPS)/class C Vps complex, an effector and guanine nucleotide exchange factor for the yeast vacuolar Rab GTPase Ypt7p. We now report reconstitution of lysis-free membrane fusion that requires purified GTP-bound Ypt7p, HOPS complex, vacuolar SNAREs, ATP hydrolysis, and the SNARE disassembly catalysts Sec17p and Sec18p. We use this …

The Brain In Its Body: Motor Control And Sensing In A Biomechanical Context, Hillel J. Chiel

Faculty Scholarship

Although it is widely recognized that adaptive behavior emerges from the ongoing interactions among the nervous system, the body, and the environment, it has only become possible in recent years to experimentally study and to simulate these interacting systems. We briefly review work on molluscan feeding, maintenance of postural control in cats and humans, simulations of locomotion in lamprey, insect, cat and salamander, and active vibrissal sensing in rats to illustrate the insights that can be derived from studies of neural control and sensing within a biomechanical context. These studies illustrate that control may be shared between the nervous system …

Protection Against Mucosal Shiv Challenge By Peptide And Helper-Dependent Adenovirus Vaccines, Eric A. Weaver, Pramod N. Nehete, Bharti P. Nehete, Stephanie J. Buchl, Donna Palmer, David C. Montefiori, Philip Ng, K. Jagannadha Sastry, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

Groups of rhesus macaques that had previously been immunized with HIV-1 envelope (env) peptides and first generation adenovirus serotype 5 (FG-Ad5) vaccines expressing the same peptides were immunized intramuscularly three times with helperdependent adenovirus (HD-Ad) vaccines expressing only the HIV-1 envelope from JRFL. No gag, pol, or other SHIV genes were used for vaccination. One group of the FG-Ad5- immune animals was immunized three times with HD-Ad5 expressing env. One group was immunized by serotype-switching with HD-Ad6, HD-Ad1, and HD-Ad2 expressing env. Previous work demonstrated that serum antibody levels against env were significantly higher in the serotype-switched group than in …

Pancreatic Cancer Cells Resistance To Gemcitabine: The Role Of Muc4 Mucin., S. Bafna, Sukhwinder Kaur, N. Momi, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND: A major obstacle to the successful management of pancreatic cancer is to acquire resistance to the existing chemotherapeutic agents. Resistance to gemcitabine, the standard first-line chemotherapeutic agent for advanced and metastatic pancreatic cancer, is mainly attributed to an altered apoptotic threshold in the pancreatic cancer. The MUC4 transmembrane glycoprotein is aberrantly overexpressed in the pancreatic cancer and recently, has been shown to increase pancreatic tumour cell growth by the inhibition of apoptosis.

METHODS: Effect of MUC4 on pancreatic cancer cells resistance to gemcitabine was studied in MUC4-expressing and MUC4-knocked down pancreatic cancer cell lines after treatment with gemcitabine by …

Mast Cell–Derived Particles Deliver Peripheral Signals To Remote Lymph Nodes, Christian A. Kunder, Ashley L. St. John, Guojie Li, Kam W. Leong, Brent Berwin, Herman F. Staats, Soman N. Abraham

Dartmouth Scholarship

During infection, signals from the periphery are known to reach draining lymph nodes (DLNs), but how these molecules, such as inflammatory cytokines, traverse the significant distances involved without dilution or degradation remains unclear. We show that peripheral mast cells, upon activation, release stable submicrometer heparin-based particles containing tumor necrosis factor and other proteins. These complexes enter lymphatic vessels and rapidly traffic to the DLNs. This physiological drug delivery system facilitates communication between peripheral sites of inflammation and remote secondary lymphoid tissues.

Assembly Of Arenavirus Envelope Glycoprotein Gpc In Detergent-Soluble Membrane Microdomains, Sudhakar S. Agnihothram, Brooke Dancho, Kenneth W. Grant, Mark L. Grimes, Douglas S. Lyles, Jack H. Nunberg

Biomedical and Pharmaceutical Sciences Faculty Publications

The family Arenaviridae includes a number of highly pathogenic viruses that are responsible for acute hemorrhagic fevers in humans. Genetic diversity among arenavirus species in their respective rodent hosts supports the continued emergence of new pathogens. In the absence of available vaccines or therapeutic agents, the hemorrhagic fever arenaviruses remain a serious public health and biodefense concern. Arenaviruses are enveloped virions that assemble and bud from the plasma membrane. In this study, we have characterized the microdomain organization of the virus envelope glycoprotein (GPC) on the cell surface by using immunogold electron microscopy. We find that Junin virus (JUNV) GPC …