Proteomic Analyses of HIV-1 Infected T-cells and the Functional Characterization of Cyclophilin B During HIV-1 Infection PDF Download
Are you looking for read ebook online? Search for your book and save it on your Kindle device, PC, phones or tablets. Download Proteomic Analyses of HIV-1 Infected T-cells and the Functional Characterization of Cyclophilin B During HIV-1 Infection PDF full book. Access full book title Proteomic Analyses of HIV-1 Infected T-cells and the Functional Characterization of Cyclophilin B During HIV-1 Infection by Jason Todd DeBoer. Download full books in PDF and EPUB format.
Author: Jason Todd DeBoer
Publisher:
ISBN:
Category :
Languages : en
Pages : 147
Get Book Here
Book Description
The human immunodeficiency virus type 1 (HIV-1) lifecycle is complex and the virus interacts with many host cellular proteins for productive replication. Mass spectrometry analysis is a powerful tool to identify cellular proteins important for HIV replication and pathogenesis. Prior proteomic studies demonstrate that HIV-1 infection perturbs the host cell proteome.
Author: Jason Todd DeBoer
Publisher:
ISBN:
Category :
Languages : en
Pages : 147
Get Book Here
Book Description
The human immunodeficiency virus type 1 (HIV-1) lifecycle is complex and the virus interacts with many host cellular proteins for productive replication. Mass spectrometry analysis is a powerful tool to identify cellular proteins important for HIV replication and pathogenesis. Prior proteomic studies demonstrate that HIV-1 infection perturbs the host cell proteome.
Author: David R. M. Graham
Publisher: Springer
ISBN: 1493965425
Category : Medical
Languages : en
Pages : 117
Get Book Here
Book Description
The development of proteomic analyses using advanced mass spectrometry techniques has revolutionized the way proteins are studied, namely, as individual molecules within a complex system. HIV-1 Proteomics: From Discovery to Clinical Application comprehensively covers protein analysis from the early classic experimental days to current state-of-the-art HIV-1 proteomics in a clear informative style that brings expert-level understanding to the novice. Discussion of important clinical applications and future directions for the field also make this an ideal read for the expert. After finishing this book, the reader will have a complete and functional understanding of protein analysis from traditional biochemistry to modern proteomics.
Author: Catherine Heather Wickham
Publisher:
ISBN:
Category :
Languages : en
Pages : 0
Get Book Here
Book Description
The human immunodeficiency virus (HIV) is the causative agent of acquired immune deficiency syndrome (AIDS), a condition characterized by depletion of CD4+ T cells and other immune system dysfunctions. Due to its widespread geographic distribution and ease of 4 transmission, HIV has become a serious global healthcare concern. HIV-1 subtype C (HIV-1-C) 5 is of particular interest since it is the most rapidly expanding and is especially prevalent in 6 southern Africa. In addition, HIV-1-C is poorly studied in comparison to other subtypes. Despite HIV being extensively researched, much is still unknown about the host cell response 8 to infection at a molecular level and how this might be exploited for therapeutic intervention. Therefore, the purpose of this study was to use microarray-based transcriptomic analysis to gain an unbiased perspective of the host cell response in CD4+ T lymphocytes and macrophages when exposed to primary HIV-1-C viruses of different tropisms (R5-tropic, X4- tropic, dual-tropic). In order to achieve this overall aim, we first needed to develop and optimize protocols for the culture of primary HIV-1-C strains. A p24 ELISA assay was used to confirm successful viral replication, followed by functional titration using the GHOST reporter cell line. We found that the efficiency of replication of primary viral isolates was highly stochastic. While many of the strains cultured suffered severe losses of infectivity, we managed to produce infective stocks of dual-tropic and X4-tropic isolates. We next aimed to optimize cell culture protocols for CD4+ T lymphocytes and macrophages that would ensure maximal susceptibility to HIV. Since activation of CD4+ T cells is reported to enhance viral replication, we assessed the efficacy of various activation protocols. We found that antibody- mediated activation was highly successful. Flow cytometric analysis revealed increased cell proliferation and CD25 expression. In addition, CD4+ T-cell activation dramatically increased CXCR4 surface expression while CCR5 expression was diminished. Infection experiments with our dual-tropic isolate confirmed that these cells were susceptible to infection. In order to optimize macrophage cell culture conditions, we compared the effects of differentiation under the influence of different growth factors (M-CSF or GM-CSF). Successful differentiation was determined by phenotypic analysis using flow cytometry coupled with a functional phagocytosis assay. Additional analysis of co-receptor expression revealed extremely low levels of CXCR4 and relatively high CCR5 expression in both macrophage populations. The differentiated macrophages were completely refractory to infection with our dual-tropic isolate, making them unsuitable for further experiments. The final component of the study was the gene expression analysis itself, which was performed using activated CD4+ T lymphocytes exposed to a dual-tropic isolate (CM9). Differential gene expression analysis revealed altered expression patterns in a relatively small but functionally diverse group of genes involved in apoptosis, deubiquitination, transcriptional regulation and immune system functions. Apoptosis and deubiquitination were identified as statistically overrepresented functional pathways in our subsequent GO-based analysis. Comparison of our findings with previous studies performed using HIV-1-B seems to indicate that while many of the genes observed in our study have not specifically been detected previously, they do tend to belong to similar pathways.
Author: Armstrong M. Murira
Publisher:
ISBN:
Category :
Languages : en
Pages : 321
Get Book Here
Book Description
A central focus in the pursuit of an effective vaccine against HIV-1 is the induction of broadly neutralizing (bNt) antibodies (Abs). However, these Abs are rarely elicited in natural infection and the immunological processes that drive this occurrence are not clearly defined. Modulation of the immunological environment during the chronic phase of infection provides a plausible mechanism by which bNt Abs are elicited and also advances the possibility that vaccine design should account for the immune response specific to this phase. Thus, the work presented here seeks to characterize the chronic phase of the humoral immune response to gain insight into the immunological mechanisms that generate bNt-Ab responses. First, disturbances in B-cell distribution in HIV+ individuals were evaluated using a computational algorithm, flowType, compared to a manual-analysis tool. In addition to yielding similar results to manual analysis, flowType revealed dysregulation of novel B-cell subsets in HIV, providing a representation of the global extent of HIV-associated B-cell dysregulation. Second, changes in B-cell distribution and serum reactivity were compared between HIV+ individuals who followed different clinical courses and individuals with the autoimmune disease, systemic lupus erythematosus (SLE). B-cell dysregulation was evident in both cohorts, though more extensive in HIV. Sera from HIV+ individuals with increased viral load, as well as SLE patients, displayed significant polyreactivity as compared to HIV+ sera from those controlling their infections. These results illustrate that despite similarities in cellular perturbations, the Ab response against HIV is antigen driven rather than autoimmune. In addition, immunogenetic analyses of B-cell repertoires of HIV+ individuals demonstrated perturbations within antigen-inexperienced naïve B cells as well as increased somatic-mutation levels, which were observed in the effector B-cell subpopulations. Finally, a murine model for chronic infection was developed using immunization with filamentous bacteriophage as a model virus-like particle. Functional analyses of CD138+ plasma cells showed that a single immunization elicited innate-like and type-1 T-cell independent (TI-1) B-cell responses, and prolonged immunization resulted in perturbations reminiscent of those observed in chronic infections (i.e., plasma-cell exhaustion). Preliminary data from transcriptomic analyses of plasma cells from different time points after immunization suggests immunophenotypic differences within the population, indicating either developmental changes, or selection from different precursor populations. Collectively, the data provide deeper insight into changes occurring in short-term and chronic humoral immune responses, as well as establishing a functional animal model that may be used to probe these features further.
Author: Ika N. Kadariswantiningsih
Publisher:
ISBN:
Category :
Languages : en
Pages :
Get Book Here
Book Description
The underlying mechanism responsible for the development of broadly neutralizing antibodies (bNAbs) in natural infection is poorly understood. Current findings suggest that a sufficient help of CD4+ T cells to B cells is required in the development of bNAbs. At the clinical level, it is unclear whether bNAbs generating individuals exhibit more robust HIV-1-specific CD4+ T cells responses, thereby providing better help to B cells during infection. We hypothesized bNAbs response generating individuals to possess superior qualitative characteristics in their HIV-1-specific CD4+ T cells responses compared to non-neutralizers. In this study, in vitro stimulation assay that allows the evaluation of the combined CD4-orchestrated cellular immune response to HIV-1 antigens was performed. CD8+ depleted peripheral blood mononuclear cells (PBMCs) of chronically HIV-infected subjects with different capability of generating bNAbs response were stimulated with Gag peptide pools for 48 hours. Qualitative characteristics of HIV-1-specific CD4+ T cells are analyzed based on 34 chemokines and cytokines secretion in the supernatant. HIV-1-specific CD4+ T cells from broad neutralizers showed to have a unique capacity to stimulate production of the cardinal cytokine CXCL13 that has been previously associated with germinal center formation and development of broadly neutralizing antibodies against HIV. Linear discriminant analysis (LDA) and partial least square discriminant analysis (PLSDA) also showing CXCL13 to be positively correlated with neutralization. Immunofluorescence staining of the lymph node section showed that CXCL13 was exclusively found in the follicle. Although CXCL13 is thought to be a natural ligand for CXCR5, not all cells that expressed CXCL13 have CXCR5 co-staining. It may suggest that CXCL13 is not exclusively expressed by CXCR5+ CD4+ T cells in the germinal centers and other follicular cell subset may contribute.
Author: Katherine Joy Nicholas
Publisher:
ISBN:
Category : Electronic dissertations
Languages : en
Pages : 138
Get Book Here
Book Description
Author: Guido Silvestri
Publisher: Springer
ISBN: 303002816X
Category : Medical
Languages : en
Pages : 253
Get Book Here
Book Description
This volume summarizes recent advances in understanding the mechanisms of HIV-1 latency, in characterizing residual viral reservoirs, and in developing targeted interventions to reduce HIV-1 persistence during antiretroviral therapy. Specific chapters address the molecular mechanisms that govern and regulate HIV-1 transcription and latency; assays and technical approaches to quantify viral reservoirs in humans and animal models; the complex interchange between viral reservoirs and the host immune system; computational strategies to model viral reservoir dynamics; and the development of therapeutic approaches that target viral reservoir cells. With contributions from an interdisciplinary group of investigators that cover a broad spectrum of subjects, from molecular virology to proof-of-principle clinical trials, this book is a valuable resource for basic scientists, translational investigators, infectious-disease physicians, individuals living with HIV/AIDS and the general public.
Author: Steven G.E. Marsh
Publisher: Elsevier
ISBN: 0080542506
Category : Medical
Languages : en
Pages : 413
Get Book Here
Book Description
The HLA FactsBook presents up-to-date and comprehensive information on the HLA genes in a manner that is accessible to both beginner and expert alike. The focus of the book is on the polymorphic HLA genes (HLA-A, B, C, DP, DQ, and DR) that are typed for in clinical HLA laboratories. Each gene has a dedicated section in which individual entries describe the structure, functions, and population distribution of groups of related allotypes. Fourteen introductory chapters provide a beginner's guide to the basic structure, function, and genetics of the HLA genes, as well as to the nomenclature and methods used for HLA typing. This book will be an invaluable reference for researchers studying the human immune response, for clinicians and laboratory personnel involved in clinical and forensic HLA typing, and for human geneticists, population biologists, and evolutionary biologists interested in HLA genes as markers of human diversity. Introductory chapters provide good general overview of HLA field for novice immunologists and geneticists Up-to-date, complete listing of HLA alleles Invaluable reference resource for immunologists, geneticists, and cell biologists Combines both structural and functional information, which has never been compiled in a single reference book previously Serological specificity of allotypes Identity of material sequenced including ethnic origin Database accession numbers Population distribution Peptide binding specificities T cell epitopes Amino acid sequences of allotypes Key references
Author: Marcos Roberto de Oliveira
Publisher: Academic Press
ISBN: 0128215836
Category : Science
Languages : en
Pages : 808
Get Book Here
Book Description
Mitochondrial Physiology and Vegetal Molecules: Therapeutic potential of natural compounds on mitochondrial health provides a comprehensive overview of mitochondrial physiology throughout the human life span, as well as the effect of molecules of vegetal origin on mitochondrial health. The editor has lined up a team of worldwide experts to cover the most exciting and high-impact advancements of research in this area. This book is structured into two parts that provide a balance of both foundational and applied content. Part I provides an overview of mitochondrial physiology including its structure, dynamics, biogenesis, membranes, DNA transcription, and translation in the mitochondria. Part I also covers other themes such as apoptosis. Part II then covers the effect of specific vegetable-derived molecules on mitochondrial health, including anthocyanins, caffeine, cannabinoids, carnosic and rosmarinic acids, citrus flavonoids, polyphenols, pterostilbene, resveratrol, and sulforaphane, among others. Mitochondrial Physiology and Vegetal Molecules: Therapeutic potential of natural compounds on mitochondrial health is a complete resource for researchers in this exciting field. Its comprehensive coverage makes it particularly interesting to bioscience researchers willing to understand the foundations of mitochondrial physiology throughout the human life span. Clinician researchers, MDs, nutritionists, pharmacologists, and sports scientists may be attracted to the detailed information on the health effects of vegetal origin molecules on the organelle. - Contains detailed information on plant products and their effect on mitochondria - Proposes therapies and reviews mechanisms of absorption at the cellular level - Discusses the limited bioavailability of plant molecules/compounds in the human organism - Includes coverage of specific conditions such as Sports and affective disorders, among others - Presents the protective effects of plant products in mitochondrial health through all stages of life
Author: Vladimir Uversky
Publisher: John Wiley & Sons
ISBN: 0470618310
Category : Science
Languages : en
Pages : 532
Get Book Here
Book Description
This book provides up-to-date information on experimental and computational characterization of the structural and functional properties of viral proteins, which are widely involved in regulatory and signaling processes. With chapters by leading research groups, it features current information on the structural and functional roles of intrinsic disorders in viral proteomes. It systematically addresses the measles, HIV, influenza, potato virus, forest virus, bovine virus, hepatitis, and rotavirus as well as viral genomics. After analyzing the unique features of each class of viral proteins, future directions for research and disease management are presented.
