Medical Immunology Commons^™

Evaluation Of Clinical Outcomes Of Prophylactic Versus Preemptive Cytomegalovirus Strategy In Liver Transplant Recipients, Ifeanyi Onor, Sarah Todd, Erika Meredith, Sebastian Perez, Aneesh Mehta, G Lyon, Stuart Knechtle, Steven Hanish

Faculty and Staff Publications

Cytomegalovirus (CMV) is a major cause of morbidity and mortality following solid organ transplantation (SOT). Two strategies, prophylactic, and preemptive have emerged for the prevention of CMV infection and disease after SOT. This retrospective chart review of two liver transplant cohorts: prophylactic and preemptive, compares the clinical impact of transitioning from prophylactic to preemptive strategy. The primary outcome is the incidence of CMV viremia at 3-and 6-months post-transplant. Secondary outcomes include: incidence of CMV tissue-invasive disease, acute cellular rejection, leukopenia and neutropenia, opportunistic infection rates, hospital readmission rates, and mortality at 3-and 6-months post-transplant. A total of 109 patients were …

Microproteinuria During Opisthorchis Viverrini Infection: A Biomarker For Advanced Renal And Hepatobiliary Pathologies From Chronic Opisthorchiasis, Prasert Saichua, Paiboon Sithithaworn, Amar R. Jariwala, David J. Diemert, Jiraporn Sithithaworn, Banchob Sripa, Thewarach Laha, Eimorn Mairiang, Chawalit Pairojkul, Maria V. Periago, Narong Khuntikeo, Jason Mulvenna, Jeffrey M. Bethony

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Approximately 680 million people are at risk of infection with Opisthorchis viverrini (OV) andClonorchis sinensis, with an estimated 10 million infected with OV in Southeast Asia alone. While opisthorchiasis is associated with hepatobiliary pathologies, such as advanced periductal fibrosis (APF) and cholangiocarcinoma (CCA), animal models of OV infection show that immune-complex glomerulonephritis is an important renal pathology that develops simultaneously with hepatobiliary pathologies. A cardinal sign of immune-complex glomerulonephritis is the urinary excretion of immunoglobulin G (IgG) (microproteinuria). In community-based studies in OV endemic areas along the Chi River in northeastern Thailand, we observed that over half of …

The Role Of Indoleamine 2,3-Dioxygenase In Lp-Bpm5 Murine Retroviral Disease Progression, Megan A. O'Connor, William R. Green

Dartmouth Scholarship

Indoleamine 2,3-dioxygenase (IDO) is an immunomodulatory intracellular enzyme involved in tryptophan degradation. IDO is induced during cancer and microbial infections by cytokines, ligation of co-stimulatory molecules and/or activation of pattern recognition receptors, ultimately leading to modulation of the immune response. LP-BM5 murine retroviral infection induces murine AIDS (MAIDS), which is characterized by profound and broad immunosuppression of T- and B-cell responses. Our lab has previously described multiple mechanisms regulating the development of immunodeficiency of LP-BM5-induced disease, including Programmed Death 1 (PD-1), IL-10, and T-regulatory (Treg) cells. Immunosuppressive roles of IDO have been demonstrated in other retroviral models, suggesting a possible …

Oral Transmission Of Listeria Monocytogenes In Mice Via Ingestion Of Contaminated Food, Elsa N. Bou Ghanem, Tanya Myers-Morales, Grant S. Jones, Sarah E. F. D'Orazio

Microbiology, Immunology, and Molecular Genetics Faculty Publications

L. monocytogenes are facultative intracellular bacterial pathogens that cause food borne infections in humans. Very little is known about the gastrointestinal phase of listeriosis due to the lack of a small animal model that closely mimics human disease. This paper describes a novel mouse model for oral transmission of L. monocytogenes. Using this model, mice fed L. monocytogenes-contaminated bread have a discrete phase of gastrointestinal infection, followed by varying degrees of systemic spread in susceptible (BALB/c/By/J) or resistant (C57BL/6) mouse strains. During the later stages of the infection, dissemination to the gall bladder and brain is observed. The …

Competition For Antigen Selects T Cell Responses That Undergo Memory Inflation And Maintains Clonal Dominance During Mcmv Infection, Holly Turula, Lila A. Farrington, Corinne Smith, Ann B. Hill, Christopher M Snyder

Department of Microbiology and Immunology Faculty Papers

Cytomegalovirus (CMV) establishes a life-long, persistent/latent infection. Continuous immune surveillance by CMV-specific CD8+ T cells results in their accumulation over time, a process called “memory inflation”. These “inflationary” T cells migrate systemically and comprise the largest T cell populations in humans, making CMV-based vaccines attractive. Why T cells specific for only some CMV-derived epitopes undergo inflation is unclear. We found previously that recombinant murine (M)CMV expressing the SIINFEKL peptide only induced inflation of SIINFEKL-specific T cells, in contrast to wild-type MCMV infection. We show here that:

• Co-infecting mice with viruses expressing and lacking SIINFEKL enabled T cells with multiple specificities …

Effect Of Coconut Oil On Ulcerative Colitis In The Mouse Model, Pranav Chandra Alok

Masters Theses & Specialist Projects

Ulcerative colitis (UC) is a chronic disease of the colon or large intestine that causes inflammation and ulceration of the inner lining of the colon and rectum. In patients with ulcerative colitis, the body’s immune system overreacts and the body mistakes food, bacteria or other internal materials in the colon for an invading substance. The immune system attacks the material, thus irritating the colon. Limited knowledge of inflammatory conditions coupled with a narrow range of therapeutic options necessitates investigating the role of natural products. This study describes the effect of natural coconut oil on chemically-induced acute and chronic disease in …

Role Of Mir-19a Released By Inflammatory Breast Cancer Cells In The Regulation Of Dendritic Cell Functions: In Vitro Model Of Crosstalk In The Tumor Microenvironment Of Inflammatory Breast Cancer, Simone Anfossi

Dissertations and Theses (Open Access)

Inflammatory breast cancer (IBC) is a rare but very aggressive form of locally advanced breast cancer (1-6% of total breast cancer patients in United States), with a 5-year overall survival rate of only 40.5%, compared with 85% of the non-IBC patients. So far, a unique molecular signature for IBC able to explain the dramatic differences in the tumor biology between IBC and non-IBC has not been identified. As immune cells in the tumor microenvironment plays an important role in regulating tumor progression, we hypothesized that tumor-associated dendritic cells (TADC) may be responsible for regulating the development of the aggressive characteristics …

Virologic Factors Contributing To The Genetic Diversification Of Influenza Viruses Circulating In North American Swine, Thomas Paul Fabrizio Ii

Theses and Dissertations (ETD)

The purpose of this study was to determine mechanisms of reassortment of swine influenza viruses and determine if certain reassortant gene combinations can drive evolution and host adaptation in the context of the triple reassortant internal gene (TRIG) cassette. The TRIG contains a unique combination of a human polymerase basic 1 (PB1) gene with avian polymerase basic 2 (PB2) and polymerase acidic (PA) genes. The remaining internal genes, nucleoprotein (NP), matrix (M), and non-structural (NS) are of swine origin. This differs considerably from classical swine lineage viruses which are drifted variants of the 1918 pandemic with all swine origin genes. …

Stimulation Through Tlr4 Increases Fviii Inhibitor Formation In A Mouse Model Of Hemophilia A, Claire K. Holley

Dissertations and Theses (Open Access)

Hemophilia A is a clotting disorder caused by functional factor VIII (FVIII) deficiency. About 25% of patients treated with therapeutic recombinant FVIII develop antibodies (inhibitors) that render subsequent FVIII treatments ineffective. The immune mechanisms of inhibitor formation are not entirely understood, but circumstantial evidence indicates a role for increased inflammatory response, possibly via stimulation of Toll-like receptors (TLRs), at the time of FVIII immunization. I hypothesized that stimulation through TLR4 in conjunction with FVIII treatments would increase the formation of FVIII inhibitors. To test this hypothesis, FVIII K.O. mice were injected with recombinant human FVIII with or without concomitant doses …

Characterization Of Differentiation And Prognostic Biomarkers On Cd8+ Tumor-Infiltrating Lymphocytes In Metastatic Melanoma, Richard C. Wu

Dissertations and Theses (Open Access)

CD8⁺ cytotoxic T lymphocytes (CTL) frequently infiltrate tumors, yet most melanoma patients fail to undergo tumor regression. We studied the differentiation of the CD8⁺ tumor-infiltrating lymphocytes (TIL) from 44 metastatic melanoma patients using known T-cell differentiation markers. We also compared CD8⁺ TIL against the T cells from matched melanoma patients’ peripheral blood. We discovered a novel subset of CD8⁺ TIL co-expressing early-differentiation markers, CD27, CD28, and a late/senescent CTL differentiation marker, CD57. This CD8⁺CD57⁺ TIL expressed a cytolytic enzyme, granzyme B (GB), yet did not express another cytolytic pore-forming molecule, perforin (Perf). In …

Proteomic Studies Of The Influenza Virus-Human Cell Interactions: The Responses Of Host Cell Protein Expression To Viral Infection And The Novel Host Proteins That Interact With Virus Protein Ns1, Yimeng Wang

Graduate Theses and Dissertations

Influenza A viruses (IAVs) continue to be a threat to human health. Despite extensive studies, the mechanisms underlying the IAVs-host interactions during IAV infection remain elusive. We employed quantitative proteomic methods to systematically explore the host cell protein expression responses to IAV infection and examine the function of a critical IAV protein called NS1 by identifying its host binding partners. Specifically, we used a 2-dimentional gel electrophoresis (2-DE) based proteomic method to screen host proteins whose expression was substantially altered by IAV. One critical protein named IκB kinase-gamma (IKKγ) was found to be significantly down-regulated during IAV infection. Functional studies …

Vaccination With Human Hookworm Vaccine "Necator Americanus Aspartic Protease-1 M74" Generates Neutralizing Antibodies And A Potent Immune Response In Balb/C Mice, Amar R. Jariwala, Xi Chen, Mark S. Pearson, Brian Keegan, Jill B. Brelsford, Jordan L. Plieskatt, Alex Loukas, Bin Zhan, Peter J. Hotez, Jeffrey M. Bethony

Microbiology, Immunology, and Tropical Medicine Posters and Presentations

Backgound: Human Hookworm Infection, a neglected tropical disease infects more than 600 million people around the world. Hookworms ingest hemoglobin containing erythrocytes and Necator americanus Aspartic Protease-1 wild type (Na-APR-1wt) a hemoglobinase cleaves hemoglobin to form Heme and Globin. Globin is further digested by other gut enzymes and the nutritional end products are absorbed by the hookworm’s gut wall. Also, Heme which is toxic to hookworm is detoxified by the Necator americanus Glutathione Transferase-1 (Na-GST-1) a detoxification enzyme secreted by the gut of the hookworm. Necator americanus Aspartic Protease-1 M74 (Na-APR-1 M74) is the …

Competition For Antigen At The Level Of The Apc Is A Major Determinant Of Immunodominance During Memory Inflation In Murine Cytomegalovirus Infection., Lila A Farrington, Tameka A Smith, Finn Grey, Ann B Hill, Christopher M. Snyder

Department of Microbiology and Immunology Faculty Papers

The unique ability of CMV to drive the expansion of virus-specific T cell populations during the course of a lifelong, persistent infection has generated interest in the virus as a potential vaccine strategy. When designing CMV-based vaccine vectors to direct immune responses against HIV or tumor Ags, it becomes important to understand how and why certain CMV-specific populations are chosen to inflate over time. To investigate this, we designed recombinant murine CMVs (MCMVs) encoding a SIINFEKL-enhanced GFP fusion protein under the control of endogenous immediate early promoters. When mice were infected with these viruses, T cells specific for the SIINFEKL …

Neuroinflammation And Psychiatric Illness, Souhel Najjar, Daniel M. Pearlman, Kenneth Alper, Amanda Najjar, Orrin Devinsky

Dartmouth Scholarship

Multiple lines of evidence support the pathogenic role of neuroinflammation in psychiatric illness. While systemic autoimmune diseases are well-documented causes of neuropsychiatric disorders, synaptic autoimmune encephalitides with psychotic symptoms often go under-recognized. Parallel to the link between psychiatric symptoms and autoimmunity in autoimmune diseases, neuroimmunological abnormalities occur in classical psychiatric disorders (for example, major depressive, bipolar, schizophrenia, and obsessive-compulsive disorders). Investigations into the pathophysiology of these conditions traditionally stressed dysregulation of the glutamatergic and monoaminergic systems, but the mechanisms causing these neurotransmitter abnormalities remained elusive. We review the link between autoimmunity and neuropsychiatric disorders, and the human and experimental evidence …

An Ethical Analysis Of Incentives As “Nudges” Toward Better Health Outcomes: A Case Study Of Seva Mandir’S Immunization Program In Rural Udaipur, Julika Kaplan

Independent Study Project (ISP) Collection

Seva Mandir, a non-governmental organization working on tribal development issues in the Udaipur District of India, offers pregnant women and mothers one kilogram of lentils for every visit they make to the organization’s monthly immunization camps. This study assesses whether it is ethical to use incentive-based systems, as opposed to empowerment through health education, to “nudge” the rural poor in Udaipur toward immunization. The information presented in this study is based on twenty-nine interviews with pregnant women and mothers of children less than two years old conducted during six field visits to Seva Mandir’s immunization camps. Through data obtained from …

Interventions To Reduce Neonatal Mortality From Neonatal Tetanus In Low And Middle Income Countries - A Systematic Review, Adeel Ahmed Khan, Aysha Zahidie, F. Rabbani

Community Health Sciences

Background

In 1988, WHO estimated around 787,000 newborns deaths due to neonatal tetanus. Despite few success stories majority of the Low and Middle Income Countries (LMICs) are still struggling to reduce neonatal mortality due to neonatal tetanus. We conducted a systematic review to understand the interventions that have had a substantial effect on reducing neonatal mortality rate due to neonatal tetanus in LMICs and come up with feasible recommendations for decreasing neonatal tetanus in the Pakistani setting.

Methods

We systemically reviewed the published literature (Pubmed and Pubget databases) to identify appropriate interventions for reducing tetanus related neonatal mortality. A total …

Improving Health Outcomes For Children (Ihoc) First Steps Phase I Initiative: Improving Immunizations For Children And Adolescents, Kimberley S. Fox Mpa, Carolyn E. Gray Mph

Population Health & Health Policy

This report, co-authored by Kimberley Fox and Carolyn Gray, provides a final evaluation of the initial phase of First STEPS (Strengthening Together Early Preventive Services), a learning collaborative led by Maine Quality Counts to support 24 pediatric and family practices in improving their childhood immunization rates. The evaluation found that all participating practices had higher immunization rates after participating in First STEPS. On average, overall child immunization rates increased by 5.1% at 12 months and 7.1% at 15 months, and average immunization rates across practices increased significantly from 74.2% to 81.3%. Practices also reported significant improvement in the use of …

Flagellar Motility Is A Key Determinant Of The Magnitude Of The Inflammasome Response To Pseudomonas Aeruginosa, Yash R. Patankar, Rustin R. Lovewell, Matthew E. Poynter, Jeevan Jyot, Barbara I. Kazmierczak, Brent Berwin

Dartmouth Scholarship

We previously demonstrated that bacterial flagellar motility is a fundamental mechanism by which host phagocytes bind and ingest bacteria. Correspondingly, loss of bacterial motility, consistently observed in clinical isolates from chronic Pseudomonas aeruginosa infections, enables bacteria to evade association and ingestion of P. aeruginosa by phagocytes both in vitro and in vivo. Since bacterial interactions with the phagocyte cell surface are required for type three secretion system-dependent NLRC4 inflammasome activation by P. aeruginosa, we hypothesized that reduced bacterial association with phagocytes due to loss of bacterial motility, independent of flagellar expression, will lead to reduced inflammasome activation. Here we report …

Cd4 And Cd8 T Cells Directly Recognize Murine Gammaherpesvirus 68-Immortalized Cells And Prevent Tumor Outgrowth, Xiaozhan Liang, Rebecca L. Crepeau, Weijun Zhang, Samuel H. Speck, Edward J. Usherwood

Dartmouth Scholarship

There has been extensive research regarding T cell recognition of Epstein-Barr virus-transformed cells; however, less is known regarding the recognition of B cells immortalized by gamma-2 herpesviruses. Here we show that B cells immortalized by murine gammaherpesvirus 68 (MHV-68, γHV-68) can be controlled by either CD4 or CD8 T cells in vivo. We present evidence for the direct recognition of infected B cells by CD4 and CD8 T cells. These data will help in the development of immunotherapeutic approaches combating gamma-2 herpesvirus-related disease.

Enhanced Phagocytic Activity Of Hiv-Specific Antibodies Correlates With Natural Production Of Immunoglobulins With Skewed Affinity For Fcγr2a And Fcγr2b, Margaret E. Ackerman, Anne-Sophie Dugast, Elizabeth G. Mcandrew, Stephen Tsoukas

Dartmouth Scholarship

While development of an HIV vaccine that can induce neutralizing antibodies remains a priority, decades of research have proven that this is a daunting task. However, accumulating evidence suggests that antibodies with the capacity to harness innate immunity may provide some protection. While significant research has focused on the cytolytic properties of antibodies in acquisition and control, less is known about the role of additional effector functions. In this study, we investigated antibody-dependent phagocytosis of HIV immune complexes, and we observed significant differences in the ability of antibodies from infected subjects to mediate this critical effector function. We observed both …

Hirsutella Sinensis Mycelium Suppresses Interleukin-1b And Interleukin-18 Secretion By Inhibiting Both Canonical And Non-Canonical Inflammasomes, Tsung-Teng Huang, Kowit-Yu Chong, David M. Ojcius, Yi-Hui Wu, Yun-Fei Ko, Cheng-Yeu Wu, Jan Martel, Chia-Chen Lu, Hsin-Chih Lai, John Ding-E. Young

All Dugoni School of Dentistry Faculty Articles

Cordyceps sinensis is a medicinal mushroom used for centuries in Asian countries as a health supplement and tonic. Hirsutella sinensis—the anamorphic, mycelial form of C. sinensis—possesses similar properties, and is increasingly used as a health supplement. Recently, C. sinensis extracts were shown to inhibit the production of the pro-inflammatory cytokine IL-1β in lipopolysaccharide-treated macrophages. However, the molecular mechanism underlying this process has remained unclear. In addition, whether H. sinensis mycelium (HSM) extracts also inhibit the production of IL-1β has not been investigated. In the present study, the HSM extract suppresses IL-1β and IL-18 secretion, and ATP-induced activation of caspase-1. Notably, …

Break Out: Urogenital Schistosomiasis And Schistosoma Haematobium Infection In The Post-Genomic Era, Paul J. Brindley, Peter J. Hotez

Microbiology, Immunology, and Tropical Medicine Faculty Publications

No abstract provided.

First Steps Phase I Initiative: Improving Immunizations For Children And Adolescents, Kimberley S. Fox Mpa, Carolyn E. Gray Mph

Population Health & Health Policy

This evalution report, authored by research staff at the USM Muskie School, assesses the change in immunization rates in participating pediatric and family practices that serve a high volume of children insured by MaineCare (Maine's Medicaid system). The authors also summarize lessons learned in implementing changes in practices and challenges in using the immunization measures at the practice-level to inform quality improvement.

Effects Of Treatment On Ige Responses Against Parasite Allergen-Like Proteins And Immunit To Reinfection In Childhood Schistosome And Hookworm Coinfections, Angela Pinot De Moira, Frances M. Jones, Shona Wilson, Edridah Tukahebwa, Colin M. Fitzsimmons, Joseph K. Mwatha, Jeffrey M. Bethony, Narcis B. Kabatereine, David W. Dunne

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Naturally occurring human immunity to both schistosomiasis and hookworm infection has been associated with IgE responses against parasite allergen-like proteins. Since the two helminths frequently coinfect the same individuals, there is growing advocacy for their concurrent treatment. However, both helminths are known to exert strong immunomodulatory effects; therefore, coinfected individuals could have immune responses different from those characteristically seen in monoinfected individuals. In this study, we measured changes in IgE, IgG1, and IgG4 responses to schistosome and hookworm antigens, including the allergen-like proteins Schistosoma mansoni tegumental-allergen-like 1 protein (SmTAL1), SmTAL2, and Necator americanus Ancylostoma-secreted protein-2 (Na-ASP-2), following concurrent …

Htlv Tax: A Fascinating Multifunctional Co-Regulator Of Viral And Cellular Pathways, Robert Currer, Rachel Van Duyne, Elizabeth Jaworski, Irene Guendel, Gavin Sampey, Ravi Das, Aarthi Narayanan, Fatah Kashanchi

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Human T-cell lymphotropic virus type 1 (HTLV-1) has been identified as the causative agent of adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The virus infects between 15 and 20 million people worldwide of which approximately 2–5% develop ATL. The past 35 years of research have yielded significant insight into the pathogenesis of HTLV-1, including the molecular characterization of Tax, the viral transactivator, and oncoprotein. In spite of these efforts, the mechanisms of oncogenesis of this pleiotropic protein remain to be fully elucidated. In this review, we illustrate the multiple oncogenic roles of Tax by summarizing a recent …

Transcriptional Responses Of In Vivo Praziquantel Exposure In Schistosomes Identifies A Functional Role For Calcium Signalling Pathway Member Camkii, Hong You, Donald P. Mcmanus, Wei Hu, Michael J. Smout, Paul J. Brindley, Geoffrey N. Gobert

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Treatment for clinical schistosomiasis has relied centrally on the broad spectrum anthelmintic praziquantel; however, there is limited information on its mode of action or the molecular response of the parasite. This paper presents a transcriptional and functional approach to defining the molecular responses of schistosomes to praziquantel. Differential gene expression in Schistosoma japonicum was investigated by transcriptome-wide microarray analysis of adult worms perfused from infected mice after 0.5 to 24 hours after oral administration of sub-lethal doses of praziquantel. Genes up-regulated initially in male parasites were associated with “Tegument/Muscle Repair” and “Lipid/Ion Regulation” functions and were followed by “Drug Resistance” …

Thrombospondin-1 Signaling Through Cd47 Inhibits Self-Renewal By Regulating C-Myc And Other Stem Cell Transcription Factors, Sukhbir Kaur, David R. Soto-Pantoja, Erica V. Stein, Chengyu Liu, Abdel G. Elkahloun, Michael L. Pendrak, Alina Nicolae, Satya P. Singh, Zuqin Nie, David Levens, Jeffrey S. Isenberg, David D. Roberts

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Signaling through the thrombospondin-1 receptor CD47 broadly limits cell and tissue survival of stress, but the molecular mechanisms are incompletely understood. We now show that loss of CD47 permits sustained proliferation of primary murine endothelial cells, increases asymmetric division, and enables these cells to spontaneously reprogram to form multipotent embryoid body-like clusters. c-Myc, Klf4, Oct4, and Sox2 expression is elevated in CD47-null endothelial cells, in several tissues of CD47- and thrombospondin-1-null mice, and in a human T cell line lacking CD47. CD47 knockdown acutely increases mRNA levels of c-Myc and other stem cell transcription factors in cells and in vivo, …

Cd56negcd16+ Nk Cells Are Activated Mature Nk Cells With Impaired Effector Function During Hiv-1 Infection, Jeffrey M. Milush, Sandra López-Vergès, Vanessa A. York, Steven G. Deeks, Jeffrey N. Martin, Frederick M. Hecht, Lewis L. Lanier, Douglas F. Nixon

Microbiology, Immunology, and Tropical Medicine Faculty Publications

BACKGROUND: A subset of CD3(neg)CD56(neg)CD16⁺ Natural Killer (NK) cells is highly expanded during chronic HIV-1 infection. The role of this subset in HIV-1 pathogenesis remains unclear. The lack of NK cell lineage-specific markers has complicated the study of minor NK cell subpopulations.

RESULTS: Using CD7 as an additional NK cell marker, we found that CD3(neg)CD56(neg)CD16⁺ cells are a heterogeneous population comprised of CD7⁺ NK cells and CD7(neg) non-classical myeloid cells. CD7⁺CD56(neg)CD16⁺ NK cells are significantly expanded in HIV-1 infection. CD7⁺CD56(neg)CD16⁺ NK cells are mature and express KIRs, the C-type lectin-like receptors NKG2A and NKG2C, and natural cytotoxicity receptors similar to …

Factors That Lead To The Immunotherapy Gap In Multiple Sclerosis Testing, Karthika Solai

AUCTUS: The Journal of Undergraduate Research and Creative Scholarship

Multiple sclerosis is a disease that affects the central nervous system. Most doctors and scientists believe that it is an autoimmune disease. Simply put, the immune system attacks the nerves in a person’s body, thereby causing myelin damage, inflammation, and neurodegeneration. The plaque that then builds up on the nerves is scar tissue created when the wounds made by the immune system heal. It is this plaque that inhibits communication between the axons in the body and causes the symptoms of MS, which includes problems with movement, pain, vision problems, trouble swallowing, fatigue, and heat sensitivity (Baker et al., 2011, …

Molecular Architecture Of The Uncleaved Hiv-1 Envelope Glycoprotein Trimer, Youdong Mao, Luis Castillo-Menendez, Liping Wang, Christopher Gu, Alon Herschhorn, Anik Désormeaux, Andrés Finzi, Shi-Hua Xiang, Joseph Sodroski

Nebraska Center for Virology: Faculty Publications

The human immunodeficiency virus (HIV-1) envelope glycoprotein (Env) trimer, a membrane-fusing machine, mediates virus entry into host cells and is the sole virusspecific target for neutralizing antibodies. Binding the receptors, CD4 and CCR5/CXCR4, triggers Env conformational changes from the metastable unliganded state to the fusion-active state. We used cryo-electron microscopy to obtain a 6-Å structure of the membranebound, heavily glycosylated HIV-1 Env trimer in its uncleaved and unliganded state. The spatial organization of secondary structure elements reveals that the unliganded conformations of both gp120 and gp41 subunits differ from those induced by receptor binding. The gp120 trimer association domains, which …