Immunology and Infectious Disease Commons^™

Resolving Bovine Viral Diarrhea Virus Subtypes From Persistently Infected U.S. Beef Calves With Complete Genome Sequence, Aspen M. Workman, Michael P. Heaton, Gregory P. Harhay, Timothy P.L. Smith, Dale M. Grotelueschen, David Sjeklocha, Bruce Brodersen, Jessica L. Petersen, Carol G. Chitko-Mckown

School of Veterinary and Biomedical Sciences: Faculty Publications

Bovine viral diarrhea virus (BVDV) is classified into 2 genotypes, BVDV-1 and BVDV-2, each of which contains distinct subtypes with genetic and antigenic variation. To effectively control BVDV by vaccination, it is important to know which subtypes of the virus are circulating and how their prevalence is changing over time. Accordingly, the purpose of our study was to estimate the current prevalence and diversity of BVDV subtypes from persistently infected (PI) beef calves in the central United States. Phylogenetic analysis of the 5′-UTR (5′ untranslated region) for 119 virus strains revealed that a majority (82%) belonged to genotype 1b, and …

New Tools To Convert Bacterial Artificial Chromosomes To A Self-Excising Design And Their Application To A Herpes Simplex Virus Type 1 Infectious Clone, Alexsia L. Richards, Patricia J. Sollars, Gregory A. Smith

School of Veterinary and Biomedical Sciences: Faculty Publications

Background: Infectious clones are fundamental tools for the study of many viruses, allowing for efficient mutagenesis and reproducible production of genetically-defined strains. For the large dsDNA genomes of the herpesviridae, bacterial artificial chromosomes have become the cloning vector of choice due to their capacity to house full-length herpesvirus genomes as single contiguous inserts. Furthermore, while maintained as plasmids in Escherichia coli, the clones can be mutated using robust prokaryotic recombination systems. An important consideration in the design of these clones is the means by which the vector backbone is removed from the virus genome upon delivery into mammalian cells. …

The Mechanistic Basis Of Hemoglobin Adaptation In The High-Flying Barheaded Goose: Insights From Ancestral Protein Resurrection, Chandrasekhar Natarajan, Amit Kumar, Hideaki Moriyama, Roy E. Weber, Angela Fago, Jay F. Storz

School of Veterinary and Biomedical Sciences: Faculty Publications

The bar-headed goose (‘BHG’, Anser indicus) is renowned for its trans-Himalayan migratory flights, and the elevated hemoglobin (Hb)-O2 affinity of this species is thought to make a key contribution to its capacity for powered flight at elevations of ~9000 m. Here we revisit the molecular basis of this text-book example of biochemical adaptation. Previous hypotheses about the molecular basis of the evolved increase in Hb-O2 affinity were tested by engineering BHGspecific mutations into recombinant human Hb. This approach can provide important insights, but one problem with such ‘horizontal’ comparisons – swapping residues between proteins of contemporary species – is that …

Maporal Hantavirus Causes Mild Pathology In Deer Mice (Peromyscus Maniculatus), Amanda Mcguire, Kaitlyn Miedema, Joseph R. Fauver, Amber Rico, Tawfik Aboellail, Sandra L. Quackenbush, Ann Hawkinson, Tony Schountz

School of Veterinary and Biomedical Sciences: Faculty Publications

Rodent-borne hantaviruses can cause two human diseases with many pathological similarities: hantavirus cardiopulmonary syndrome (HCPS) in the western hemisphere and hemorrhagic fever with renal syndrome in the eastern hemisphere. Each virus is hosted by specific reservoir species without conspicuous disease. HCPS-causing hantaviruses require animal biosafety level-4 (ABSL-4) containment, which substantially limits experimental research of interactions between the viruses and their reservoir hosts. Maporal virus (MAPV) is a South American hantavirus not known to cause disease in humans, thus it can be manipulated under ABSL-3 conditions. The aim of this study was to develop an ABSL-3 hantavirus infection model using the …

Localization Of Cd8 T Cell Epitope Within Cardiac Myosin Heavy Chain-Α334-352 That Induces Autoimmune Myocarditis In A/J Mice, Chandirasegara Massilamany, Arunakumar Gangaplara, Rakesh H. Basavalingappa, Rajkumar A. Rajasekaran, Vahid Khalilzad-Sharghi, Zhongji Han, Shadi F. Othman, David Steffen, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

Background—Cardiac myosin heavy chain-α (Myhc), an intracellular protein expressed in the cardiomyocytes, has been identified as a major autoantigen in cardiac autoimmunity. In our studies with Myhc_334-352-induced experimental autoimmune myocarditis in A/J mice (H-2a), we discovered that Myhc_334-352, supposedly a CD4 T cell epitope, also induced antigen-specific CD8 T cells that transfer disease to naïve animals.

Methods and Results—In our efforts to identify the CD8 T cell determinants, we localized Myhc_338-348 within the full length-Myhc_334-352, leading to four key findings. (1) By acting as a dual epitope, Myhc_338-348 induces both …

Note On Ehrlichia Chaffeensis, Ehrlichia Ewingii, And “Borrelia Lonestari” Infection In Lone Star Ticks (Acari: Ixodidae), Nebraska, Usa, Amanda Maegli, J. Dustin Loy, Roberto Cortinas

School of Veterinary and Biomedical Sciences: Faculty Publications

The lone star tick, Amblyomma americanum (L.) (Acari: Ixodidae), is established in southeastern Nebraska, yet the prevalence of tick-associated microorganisms is not known. An initial PCR-based analysis for Ehrlichia chaffeensis, Ehrlichia ewingii, and Borrelia infection in host-seeking adult ticks collected in southeast Nebraska was conducted. A total of 251 adult ticks collected in six sites in southeast Nebraska were tested. E. chaffeensis, E. ewingii, and Borrelia spp. were present, and the prevalence of each was approximately 1.6%. This study demonstrates that Ehrlichia spp. are present in Nebraska lone star tick populations.

Expression And Distribution Of Thiol-Regulating Enzyme Glutaredoxin 2 (Grx2) In Porcine Ocular Tissues, Bijaya Upadhyaya, Xiaoli Tian, Hongli Wu, Marjorie F. Lou

School of Veterinary and Biomedical Sciences: Faculty Publications

Glutaredoxin2 (Grx2) is a mitochondrial isozyme of the cytosolic glutaredoxin1 (thioltransferase or TTase). Both belong to the large oxidoreductase family and play an important role in maintaining thiol/disulfide redox homeostasis in the cells. Grx2 is recently found in the lens where its activities of disulfide reductase and peroxidase, similar to TTase, can protect the lens against oxidative stress. Since other eye tissues are also highly sensitive to oxidative stress, and TTase’s distribution in the eye is known, we focused on this study by investigating the Grx2 distribution in the ocular tissues in comparison to the lens. Fresh porcine eyes were …

Autoimmunity In Picornavirus Infections, Chandirasegara Massilamany, Andreas Koenig, Jay Reddy, Sally Huber, Iwona Buskiewicz

School of Veterinary and Biomedical Sciences: Faculty Publications

Enteroviruses are small, non-enveloped, positive-sense singlestrand RNA viruses, and are ubiquitously found throughout the world. These viruses usually cause asymptomatic or mild febrile illnesses, but have a propensity to induce severe diseases including type 1 diabetes and pancreatitis, paralysis and neuroinflammatory disease, myocarditis, or hepatitis. This pathogenicity may result from induction of autoimmunity to organ-specific antigens. While enterovirus-triggered autoimmunity can arise from multiple mechanisms including antigenic mimicry and release of sequestered antigens, the recent demonstration of T cells expressing dual T cell receptors arising as a natural consequence of Theiler’s virus infection is the first demonstration of this autoimmune mechanism.

Genome-Wide Search For Host Association Factors During Ovine Progressive Pneumonia Virus Infection, Jesse Thompson, Fangrui Ma, Meghan Quinn, Shi-Hua Xiang

School of Veterinary and Biomedical Sciences: Faculty Publications

Ovine progressive pneumonia virus (OPPV) is an important virus that causes serious diseases in sheep and goats with a prevalence of 36% in the USA. Although OPPV was discovered more than half of a century ago, little is known about the infection and pathogenesis of this virus. In this report, we used RNA-seq technology to conduct a genome-wide probe for cellular factors that are associated with OPPV infection. A total of approximately 22,000 goat host genes were detected of which 657 were found to have been significantly up-regulated and 889 down-regulated at 12 hours post-infection. In addition to previously known …

From Crystal Structure Of Α-Conotoxin Gic In Complex With Ac-Achbp To Molecular Determinants Of Its High Selectivity For Α3Β2 Nachr, Bo Lin, Manyu Xu, Xiaopeng Zhu, Yong Wu, Xi Liu, Dongting Zhangsun, Yuanyan Hu, Shi-Hua Xiang, Igor E. Kasheverov, Victor I. Tsetlin, Xinquan Wang, Sulan Luo

School of Veterinary and Biomedical Sciences: Faculty Publications

Acetylcholine binding proteins (AChBPs) are unique spatial homologs of the ligand-binding domains of nicotinic acetylcholine receptors (nAChRs), and they reproduce some pharmacological properties of nAChRs. X-ray crystal structures of AСhBP in complex with α-conotoxins provide important insights into the interactions of α-conotoxins with distinct nAChR subtypes. Although considerable efforts have been made to understand why α-conotoxin GIC is strongly selective for α3β2 nAChR, this question has not yet been solved. Here we present the structure of α-conotoxin GIC in complex with Aplysia californica AChBP (Ac-AChBP) at a resolution of 2.1 Å. Based on this co-crystal structure complemented with molecular docking …

From Crystal Structure Of Α-Conotoxin Gic In Complex With Ac-Achbp To Molecular Determinants Of Its High Selectivity For Α3Β2 Nachr, Bo Lin, Manyu Xu, Xiaopeng Zhu, Yong Wu, Xi Liu, Dongting Zhangsun, Yuanyan Hu, Shi-Hua Xiang, Igor E. Kasheverov, Victor I. Tsetlin, Xianquan Wang, Sulan Luo

School of Veterinary and Biomedical Sciences: Faculty Publications

Acetylcholine binding proteins (AChBPs) are unique spatial homologs of the ligand-binding domains of nicotinic acetylcholine receptors (nAChRs), and they reproduce some pharmacological properties of nAChRs. X-ray crystal structures of AСhBP in complex with α-conotoxins provide important insights into the interactions of α-conotoxins with distinct nAChR subtypes. Although considerable efforts have been made to understand why α-conotoxin GIC is strongly selective for α3β2 nAChR, this question has not yet been solved. Here we present the structure of α-conotoxin GIC in complex with Aplysia californica AChBP (Ac-AChBP) at a resolution of 2.1 Å. Based on this co-crystal structure complemented with molecular docking …

Guidelines For The Use And Interpretation Of Assays For Monitoring Autophagy (3rd Edition), Daniel J. Klionsky, Rodrigo Franco, More Than 2,000 Co-Authors

School of Veterinary and Biomedical Sciences: Faculty Publications

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes.

For example, a key point that needs to be emphasized is that …

Characterization Of The Interaction Between Basigin And The Pattern Recognition Receptor Tlr4, Josephine Michelle Brown

UNF Graduate Theses and Dissertations

Toll-like receptors (TLRs) are a major group of pattern recognition receptors expressed on the surface of immune cells that recognize molecular patterns associated with all classes of pathogenic microorganisms. TLR4 recognizes the lipopolysaccharide component of Gram-negative bacterial cell walls and is the only TLR known to induce signaling through both the MyD88 and TRIF pathways. Basigin, a ubiquitous cell adhesion molecule, is a member of the immunoglobulin superfamily that has the ability to influence cell signaling mediated by the MyD88 and TRIF pathways, the same signaling pathways induced by the TLR4 receptor protein. Analysis of the Basigin protein sequence indicates …

A Requirement For Y841 In Jak3 Enzymatic Activity And Hematopoietic Cancers, George Steven Martinez

Open Access Theses & Dissertations

A medical need exists for successfully treating people afflicted with leukemia, especially those who develop drug resistant forms. Relapse leukemia cases are particularly high within Hispanic populations where this disease is among the most frequently occurring cancer. Fourteen somatic mutations have been reported in Janus tyrosine kinase 3 (Jak3), including M511I and A573V, from patients with various forms of leukemia. To monitor drug sensitivity, a model system was developed. Indeed, many of these mutations have been shown to possess transforming ability in cell lines such as the IL-3 dependent pro-B cell line Ba/F3. As such, Ba/F3 cells were transformed to …

Phylogenetic Investigation Of Enteric Bovine Coronavirus In Ireland Reveals Partitioning Between European And Global Strains, Lynda Gunn, P. J. Collins, M. J. O'Connell, Helen O'Shea

Department of Biological Sciences Publications

Background

Bovine coronavirus is a primary cause of neonatal calf diarrhea worldwide, and is also associated with acute diarrhea in adult cattle during the winter season. There are no reports on molecular characterization of bovine coronavirus in Ireland, and little data exists apart from serological studies.

Findings

In this study, 11 neonatal (mean age 9 days) calf BCoV strains from the south of Ireland were collected over a one year period and characterized using molecular methods. The spike gene which encodes a protein involved in viral entry, infectivity and immune response shows the most variability amongst the isolates and was …

Nanoparticle Conversion To Biofilms: In Vitro Demonstration Using Serum-Derived Mineralo-Organic Nanoparticles, Tsui-Yin Wong, Hsin-Hsin Peng, Cheng-Yeu Wu, Jan Martel, David M. Ojcius, Fu-Yung Hsu, John Ding-E. Young

All Dugoni School of Dentistry Faculty Articles

Aims: Mineralo-organic nanoparticles (NPs) detected in biological fluids have been described as precursors of physiological and pathological calcifications in the body. Our main objective was to examine the early stages of mineral NP formation in body fluids. Materials & methods: A nanomaterial approach based on atomic force microscopy, dynamic light scattering, electron microscopy and spectroscopy was used. Results: The mineral particles, which contain the serum proteins albumin and fetuin-A, initially precipitate in the form of round amorphous NPs that gradually grow in size, aggregate and coalesce to form crystalline mineral films similar to the structures observed in calcified human arteries. …

Preventing Thymus Involution In K5.Cyclin D1 Transgenic Mice Sustains The Naïve T Cell Compartment With Age, Michelle L. Bolner

Dissertations and Theses (Open Access)

The thymus maintains T cell receptor (TCR) repertoire diversity through perpetual release of self-MHC restricted naive T cells. However, thymus involution during the aging process reduces naïve T cell output, leading to defective immune responsiveness to newly encountered antigens. We have found that early thymus involution precipitates the age-associated shift favoring memory T cell dominancy in young control mice. Furthermore, we have shown that age-related thymus involution is prevented in mice expressing a keratin 5 promoter-driven Cyclin D1 (K5.D1) transgene in thymic epithelial cells (TECs). Thymopoiesis occurs normally in K5.D1 transgenic thymi and sustains T cell output to prevent the …

A Synthetic Porcine Reproductive And Respiratory Syndrome Virus Strain Confers Unprecedented Levels Of Heterologous Protection, Hiep Vu, Fangrui Ma, William W. Laegreid, Asit K. Pattnaik, David Steffen, Alan R. Doster, Fernando Osorio

School of Veterinary and Biomedical Sciences: Faculty Publications

Current vaccines do not provide sufficient levels of protection against divergent porcine reproductive and respiratory syndrome virus (PRRSV) strains circulating in the field, mainly due to the substantial variation of the viral genome. We describe here a novel approach to generate a PRRSV vaccine candidate that could confer unprecedented levels of heterologous protection against divergent PRRSV isolates. By using a set of 59 nonredundant, full-genome sequences of type 2 PRRSVs, a consensus genome (designated PRRSV-CON) was generated by aligning these 59 PRRSV full-genome sequences, followed by selecting the most common nucleotide found at each position of the alignment. Next, the …

The Neurobiology Of Circadian Rhythms, Patricia J. Sollars, Gary E. Pickard

School of Veterinary and Biomedical Sciences: Faculty Publications

Daily rhythms in nature, such as the opening and closing of flowers or our patterns of sleep and wakefulness and their association with the perpetual alteration of night and day, were recognized in antiquity although their origins were not questioned until the eighteenth century. The French Astronomer Jean-Jacques d’Ortous de Mairan conducted an investigation into whether the leaves of the Mimosa plant opened in response to light.¹ While de Mairan’s experiments were the first to question the origin of such daily rhythms, Augustin Pyramus de Candolle is credited with the first suggestion that they arose through an internal timekeeping …

Eosinophils From Murine Lamina Propria Induce Differentiation Of Naïve T Cells Into Regulatory T Cells Via Tgf-Β1 And Retinoic Acid, Hong-Hu Chen, Ai-Hua Sun, David M. Ojcius, Wei-Lin Hu, Yu-Mei Ge, Xu'ai Lin, Lan-Juan Li, Jian-Ping Pan, Jie Yan

All Dugoni School of Dentistry Faculty Articles

Treg cells play a crucial role in immune tolerance, but mechanisms that induce Treg cells are poorly understood. We here have described eosinophils in lamina propria (LP) that displayed high aldehyde dehydrogenase (ALDH) activity, a rate-limiting step during all-trans retinoic acid (ATRA) synthesis, and expressed TGF-β1 mRNA and high levels of ATRA. Co-incubation assay confirmed that LP eosinophils induced the differentiation of naïve T cells into Treg cells. Differentiation promoted by LP eosinophils were inhibited by blocked either TGF-β1 or ATRA. Peripheral blood (PB) eosinophils did not produce ATRA and could not induce Treg differentiation. These data identifies LP eosinophils …

Detection And Characterization Of Mineralo-Organic Nanoparticles In Human Kidneys, Tsui-Yin Wong, Cheng-Yeu Wu, Jan Martel, Cheng-Wei Lin, Fu-Yung Hsu, David M. Ojcius, Paul Y. Lin, John Ding-E. Young

All Dugoni School of Dentistry Faculty Articles

Ectopic calcification is associated with various human diseases, including atherosclerosis, cancer, chronic kidney disease, and diabetes mellitus. Although mineral nanoparticles have been detected in calcified blood vessels, the nature and role of these particles in the human body remain unclear. Here we show for the first time that human kidney tissues obtained from end-stage chronic kidney disease or renal cancer patients contain round, multilamellar mineral particles of 50 to 1,500 nm, whereas no particles are observed in healthy controls. The mineral particles are found mainly in the extracellular matrix surrounding the convoluted tubules, collecting ducts and loops of Henle as …

Hirsutella Sinensis Mycelium Attenuates Bleomycin-Induced Pulmonary Inflammation And Fibrosis In Vivo, Tsung-Teng Huang, Hsin-Chih Lai, Yun-Fei Ko, David M. Ojcius, Ying-Wei Lan, Jan Martel, John Ding-E. Young, Kowit-Yu Chong

All Dugoni School of Dentistry Faculty Articles

Hirsutella sinensis mycelium (HSM), the anamorph of Cordyceps sinensis, is a traditional Chinese medicine that has been shown to possess various pharmacological properties. We previously reported that this fungus suppresses interleukin-1β and IL-18 secretion by inhibiting both canonical and non-canonical inflammasomes in human macrophages. However, whether HSM may be used to prevent lung fibrosis and the mechanism underlying this activity remain unclear. Our results show that pretreatment with HSM inhibits TGF-β1–induced expression of fibronectin and α-SMA in lung fibroblasts. HSM also restores superoxide dismutase expression in TGF-β1–treated lung fibroblasts and inhibits reactive oxygen species production in lung epithelial cells. Furthermore, …

Dynamic Ubiquitination Drives Herpesvirus Neuroinvasion, Nicholas J. Huffmaster, Patricia J. Sollars, Alexsia L. Richards, Gary E. Pickard, Gregory A. Smith

School of Veterinary and Biomedical Sciences: Faculty Publications

Neuroinvasive herpesviruses display a remarkable propensity to enter the nervous system of healthy individuals in the absence of obvious trauma at the site of inoculation. We document a repurposing of cellular ubiquitin during infection to switch the virus between two invasive states. The states act sequentially to defeat consecutive host barriers of the peripheral nervous system and together promote the potent neuroinvasive phenotype. The first state directs virus access to nerve endings in peripheral tissue, whereas the second delivers virus particles within nerve fibers to the neural ganglia. Mutant viruses locked in either state remain competent to overcome the corresponding …

A Forward Genetic Screen Identifies Factors Associated With Fever Pathogenesis In Plasmodium Falciparum, Phaedra J. Thomas

USF Tampa Graduate Theses and Dissertations

Infectious diseases that spread from person-to-person and continent-to-continent are a cause for concern for any health entity. One such disease is malaria, a mosquito-borne infection instigated by the protozoan parasite, Plasmodium falciparum. Hundreds of millions of people are affected annually and it is responsible for nearly 1 million deaths. It is the most fatal species causing malaria and proliferates in human red blood cells with a life cycle occurring every 48 hours. At this time, the parasite’s late stage form or schizont bursts from the erythrocyte releasing immune-inducing particles and infective forms (merozoites) into the bloodstream. The merozoites go …

Trim21 Regulates Nmi-Ifi35 Complex-Mediated Inhibition Of Innate Antiviral Response, Anshuman Das, Phat X. Dinh, Asit K. Pattnaik

School of Veterinary and Biomedical Sciences: Faculty Publications

In this study, using an immunoprecipitation coupled with mass spectrometry approach, we have identified the E3 ubiquitin ligase Trim21 as an interacting partner of IFI35 and Nmi. We found that this interaction leads to K63-linked ubiquitination on K22 residue of Nmi, but not IFI35. Using domain deletion analysis, we found that the interaction is mediated via the coiled-coil domain of Nmi and the carboxyl-terminal SPRY domain of Trim21. Furthermore, we show that depletion of Trim21 leads to significantly reduced interaction of Nmi with IFI35, which results in the abrogation of the negative regulatory function of the Nmi-IFI35 complex on innate …

Comparison Of Different Modulators That Affect Macrophage Activation In Vitro, Alda Alexa Díaz Pérez

Graduate Theses and Dissertations

Inflammation is known as a mechanism to regulate and control infections as well as promote tissue repair. Macrophages (Mф) are known to be a major cell type in the initiation, sustainability and resolution of inflammation. Moreover, Mф are essential for the remodeling process that is also known as the wound healing response. The objective of this research was to compare five modulators (acetylsalicylic acid (ASA), dexamethasone (DEX), prostaglandin E2 (PGE2), iloprost, and resolvin D1 (RvD1) for their anti-inflammatory effects on macrophages in vitro. Then, Mф phenotype in terms of gene expression and secreted cytokine response was determined. Our study compared …

Ganoderma Lucidum Reduces Obesity In Mice By Modulating The Composition Of The Gut Microbiota, Chih-Jung Chang, Chuan-Sheng Lin, Chia-Chen Lu, Jan Martel, Yun-Fei Ko, David M. Ojcius, Shun-Fu Tseng, Tsung-Ru Wu, Yi-Yuan Margaret Chen, John Ding-E. Young, Hsin-Chih Lai

All Dugoni School of Dentistry Faculty Articles

Obesity is associated with low-grade chronic inflammation and intestinal dysbiosis. Ganoderma lucidum is a medicinal mushroom used in traditional Chinese medicine with putative anti-diabetic effects. Here, we show that a water extract of Ganoderma lucidum mycelium (WEGL) reduces body weight, inflammation and insulin resistance in mice fed a high-fat diet (HFD). Our data indicate that WEGL not only reverses HFD-induced gut dysbiosis—as indicated by the decreased Firmicutes-to-Bacteroidetes ratios and endotoxin-bearing Proteobacteria levels—but also maintains intestinal barrier integrity and reduces metabolic endotoxemia. The anti-obesity and microbiota-modulating effects are transmissible via horizontal faeces transfer from WEGL-treated mice to HFD-fed mice. We further …

Expression, Localization, And Kinetic Characterization Of The Phospholipid Biosynthesis Enzyme Ctp: Phosphocholine Cytidylyltransferase From The Protozoan Parasite Leishmania Major, Justin Daniel Theodore Lange

Theses and Dissertations

The eukaryotic parasite Leishmania is the causative agent of the disease leishmaniasis. L. major is the most common of 21 species that causes visceral leishmaniasis in humans, and 30 that cause the same disease in other mammals. Visceral leishmaniasis causes fever, weight loss, and over a short amount of time, multiple organ failure, and has a 100% mortality rate within 2 years. This makes it the second largest parasitic killer in the world behind malaria. Over 90% of the worldâ??s cases of visceral leishmaniasis have been reported in underdeveloped countries of India, Bangladesh, Nepal, Sudan, Ethiopia and Brazil, with 500,000 …

Chronic Inflammation As A Result Of Hepatitis C Virus Infection: A Review Of The Literature, Samantha L. Lane

DePaul Discoveries

Approximately 170 million people are infected with Hepatitis C virus (HCV) worldwide^5,6. It is estimated that roughly 80% of those infected suffer from persistent infection with the virus; this persistence of infection is progressive, and over time can lead to fibrosis, cirrhosis, and hepatocellular carcinoma⁷. Chronic inflammation and apoptotic deregulation are both hallmarks of chronic HCV infection, and many molecular pathways are initiated in both the innate and adaptive immune responses during infection with this viral pathogen. The aim of this review was to survey some of the major molecular mechanisms responsible for the induction of …

Structural And Functional Interactions Between Bro1 Domain Of Human Alix Protein And Nucleocapsid Packaging Rna Complex From Hiv, Scott Gross

Graduate School of Biomedical Sciences Theses and Dissertations

A virus is only as powerful as its ability to spread. Enveloped retroviruses, namely HIV-1, use exocytosis pathways that normal host cells use to release particles from the plasma membrane. The main pathways of interest in this study are the Endosomal Sorting Complex Required for Transport (ESCRT) and adjacent ALIX pathways. The ESCRT pathway is especially important for degradation of receptor/cargo complexes that form Multi-Vesicular Bodies (MVBs). Currently, there is no known therapy that targets this endosomal pathway, which would prevent the spread of the virus to other cells. The virus has adapted to jump from pathway to pathway when …