Download or read book HIV 1 Latency written by Guido Silvestri and published by Springer. This book was released on 2018-10-11 with total page 253 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book HIV 1 Latency written by Guido Silvestri (Professor of pathology and laboratory medicine) and published by . This book was released on 2018 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book HIV Reservoirs written by Guido Poli and published by . This book was released on 2022 with total page 451 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book details the development of methods and models to study the HIV-1 viral reservoir with the ultimate goal of achieving a functional cure of HIV infection. Chapters are divided into six parts covering cell lines, in vitro and ex vivo primary cell models of persistent infection, in vitro and ex vivo tissue-derived models, infected animal models human immune cells, methods of detection and analysis of the reservoir, and current approaches to achieve either a functional cure or cART-free long-term remission. Written in the format of the highly successful Methods in Molecular Biology series, each chapter includes an introduction to the topic, lists necessary materials and reagents, includes tips on troubleshooting and known pitfalls, and step-by-step, readily reproducible protocols. Authoritative and cutting-edge, HIV Reservoirs: Methods and Protocols provides a comprehensive, updated collection of state-of-art methodologies and models to tackle the HIV-1 viral reservoir.
Download or read book A New Mechanism for the Generation of HIV Latency written by David Gregory Brooks and published by . This book was released on 2002 with total page 202 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book HIV Vaccines and Cure written by Linqi Zhang and published by Springer. This book was released on 2018-07-20 with total page 326 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides a comprehensive review of the major barriers to HIV cure and vaccine. It covers the fundamental virology and immunology leading to HIV transmission, protection from infection and long term HIV persistence on antiretroviral therapy. In addition, strategies being tested to eliminate persistent HIV and the rational design of vaccines to induce protective immunity are covered. This book also discusses the challenges related to the design of clinical trials for testing the safety and efficacy of these innovative approaches. This book will provide a systematic overview and also discuss controversial issues for researchers in virology and immunology, as well as practicing physicians, and scientists in the pharmaceutical industry.
Download or read book DNA Methylation and Complex Human Disease written by Michel Neidhart and published by Academic Press. This book was released on 2015-08-11 with total page 546 pages. Available in PDF, EPUB and Kindle. Book excerpt: DNA Methylation and Complex Human Disease reviews the possibilities of methyl-group-based epigenetic biomarkers of major diseases, tailored epigenetic therapies, and the future uses of high-throughput methylome technologies. This volume includes many pertinent advances in disease-bearing research, including obesity, type II diabetes, schizophrenia, and autoimmunity. DNA methylation is also discussed as a plasma and serum test for non-invasive screening, diagnostic and prognostic tests, as compared to biopsy-driven gene expression analysis, factors which have led to the use of DNA methylation as a potential tool for determining cancer risk, and diagnosis between benign and malignant disease. Therapies are at the heart of this volume and the possibilities of DNA demethylation. In cancer, unlike genetic mutations, DNA methylation and histone modifications are reversible and thus have shown great potential in the race for effective treatments. In addition, the authors present the importance of high-throughput methylome analysis, not only in cancer, but also in non-neoplastic diseases such as rheumatoid arthritis. - Discusses breaking biomarker research in major disease families of current health concern and research interest, including obesity, type II diabetes, schizophrenia, and autoimmunity - Summarizes advances not only relevant to cancer, but also in non-neoplastic disease, currently an emerging field - Describes wholly new concepts, including the linking of metabolic pathways with epigenetics - Provides translational researchers with the knowledge of both basic research and clinic applications of DNA methylation in human diseases
Download or read book Factors Important for the Establishment and Maintenance of HIV 1 Latency in CD4 T Cells written by Paula Campos Soto and published by . This book was released on 2008 with total page 85 pages. Available in PDF, EPUB and Kindle. Book excerpt: Highly active antiretroviral therapy (HAART) in individuals infected with HIV-1 often lowers plasma viremia to below detection limits. However, cessation of therapy in such individuals results in rebound of virus replication, indicating that HIV-infected cells persist. Resting, memory CD4 T cells in the blood and lymph nodes comprise the major reservoir for persistent HIV infection. To devise new efficient strategies targeted toward the eradication of the latently infected HIV reservoir, a better understanding of the molecular and cellular basis for viral latency is needed. Dr. Spina's research group has developed a unique in vitro T cell model to study HIV latency. In my thesis project, I have used and modified this cell model to investigate: 1) the cellular proliferation and activation requirements for the development of latently infected CD4 cells, and 2) the transcriptional activity of the HIV provirus in a nonproductive, persistent infection. Results from the first research phase demonstrated that HIV infection immediately prior to T cell stimulation resulted in production of the greatest number of latently infected cells. Infected cells that did not divide, or divided only a few times, following stimulation went on to form the latently infected cell pool. The vast majority of acutely infected, activated CD4 cells were not able to survive multiple rounds of cell division in combination with the cytopathic effects of HIV. Rather, the subset of CD4 cells that exhibited minimal activation, in the presence of fully-activated and productively infected T cells, survived with latent HIV infection. In the second phase of research, a sensitive qRT-PCR assay was used to examine the transcriptional activity of the HIV provirus in resting, infected CD4 cells. Multiple different species of HIV mRNA were found, with unspliced gag transcripts being the most abundant followed by singly-spliced env, total multiply-spliced, nef, and tat species. Detection of viral RNA transcription in latently infected T cells from our in vitro model has raised the possibility that HIV latency is not maintained by a simple passive mechanism, but may involve active interactions between viral products and cell processes that influence viral latency and reactivation.
Download or read book HIV 1 Integrase written by Nouri Neamati and published by John Wiley & Sons. This book was released on 2011-08-10 with total page 710 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book comprehensively covers the mechanisms of action and inhibitor design for HIV-1 integrase. It serves as a resource for scientists facing challenging drug design issues and researchers in antiviral drug discovery. Despite numerous review articles and isolated book chapters dealing with HIV-1 integrase, there has not been a single source for those working to devise anti-AIDS drugs against this promising target. But this book fills that gap and offers a valuable introduction to the field for the interdisciplinary scientists who will need to work together to design drugs that target HIV-1 integrase.
Download or read book Human Cytomegalovirus written by Thomas E. Shenk and published by Springer Science & Business Media. This book was released on 2008-05-09 with total page 477 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume has gathered some of the experts in the field to review aspects of our understanding of CMV and to offer perspectives of the current problems associated with CMV. The editors and authors hope that the chapters will lead to a better understanding of the virus that will assist in the development of new and unique antivirals, a protective vaccine, and a full understanding of CMV's involvement in human disease.
Download or read book Quantitative Phase Imaging of Cells and Tissues written by Gabriel Popescu and published by McGraw Hill Professional. This book was released on 2011-03-14 with total page 384 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cutting-edge quantitative phase imaging techniques and their applications Filled with unique, full-color images taken by advanced quantitative phase imaging (QPI), Quantitative Phase Imaging of Cells and Tissues thoroughly explores this innovative technology and its biomedical applications. An introductory background on optical imaging and traditional optical microscopy is included to illustrate concept development. The book explains how various visualization modalities can be obtained by numerical calculations. This authoritative resource reveals how to take full advantage of the unprecedented capabilities of QPI, such as rendering scattering properties of minute subcellular structures and nanoscale fluctuations in live cells. Coverage includes: Groundwork Spatiotemporal field correlations Image characteristics Light microscopy Holography Point scanning QPI methods Principles of full-field QPI Off-axis full-field methods Phase-shifting techniques Common-path methods White light techniques Fourier transform light scattering (FTLS) Current trends in QPI
Download or read book Mosaic of Autoimmunity written by Carlo Perricone and published by Academic Press. This book was released on 2019-02-15 with total page 728 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Mosaic of Autoimmunity: The Novel Factors of Autoimmune Diseases describes the multifactorial origin and diversity of expression of autoimmune diseases in humans. The term implies that different combinations of factors in autoimmunity produce varying and unique clinical pictures in a wide spectrum of autoimmune diseases. Most of the factors involved in autoimmunity can be categorized into four groups: genetic, immune defects, hormonal and environmental factors. In this book, the environmental factors are reviewed, including infectious agents, vaccines as triggers of autoimmunity, smoking and its relationship with rheumatoid arthritis, systemic lupus erythematosus, thyroid disease, multiple sclerosis and inflammatory bowel diseases. An entirely new syndrome, the autoimmune/inflammatory syndrome induced by adjuvants (ASIA), is also included, along with other diseases that are now recognized as having an autoimmune etiopathogenesis. Highlights the concept of the mosaic of autoimmune manifestations Includes new visions on unsuspected molecules Provides updated knowledge to physicians helping patients with autoimmune diseases Presents thorough, up-to-date information on specific diseases, along with clinical applications
Download or read book Human Retrovirus Protocols written by Tuofu Zhu and published by Springer Science & Business Media. This book was released on 2008-02-04 with total page 488 pages. Available in PDF, EPUB and Kindle. Book excerpt: A cutting-edge collection of basic and state-of-the-art methods optimized for investigating the molecular biology of this class of retrovirus. These readily reproducible techniques range from methods for the isolation and detection of human retroviruses to cutting-edge methods for exploring the interplay between the viruses and the host. Here, the researcher will find up-to-date techniques for the isolation and propagation of HIV, HTLV, and foamy virus from a variety of sources. There are also assays for determining the cell tropism of HIV-1, the coreceptor usage of HIV-1, and human gene expression with HIV-1 infection by microarrays, as well as for phenotyping HIV-1 infected monocytes and examining their fitness. Highlights include the detection and quantification of HIV-1 in resting CD4+, a new cloning system for making recombinent virus, cDNA microarrays, and the determination of genetic polymorphisms in two recently identified HIV-1 co-factors that are critical for HIV-1 infection.
Download or read book A Computational and Experimental Approach to Understanding HIV 1 Evolution and Latency for the Design of Improved Antiviral Therapies written by Siddharth Subhas Dey and published by . This book was released on 2012 with total page 344 pages. Available in PDF, EPUB and Kindle. Book excerpt: With 33.3 million people presently infected with Human Immunodeficiency Virus-1 (HIV-1), combined with the 2.6 million new infections and 1.8 million AIDS related death in 2009 alone, HIV-1 continues to be one of the biggest global pandemics and medical challenges of the new millennium. Although the development of antiretroviral drugs was a major advance in the treatment of patients infected with HIV-1, complete eradication of HIV-1 has not been possible due to two major obstacles. First, the high mutation rate of the virus coupled with its rapid replication rate has given rise to drug resistant strains of HIV-1. Furthermore, latent viral reservoirs that are not directly targeted by anti-viral therapies or by the immune system can reactivate at a later time preventing complete viral clearance from a patient. Compounding these difficulties is the global diversification of viral strains or subtypes that have widely differing sequences, resulting in unique gene regulation and pathogenesis. Following integration into the host genome, activation of viral gene expression results in the production of new progeny whereas the inability to activate gene expression could initiate the establishment of viral latency. Thus, a better understanding of the mechanisms and factors that regulate viral transcription is critical towards eliminating latent viral populations. Therefore, the focus of this work has been to investigate the role of both cellular and viral factors in regulating HIV-1 gene expression and latency using a combination of computational and experimental techniques. This work may help develop novel therapy targets and better treatment regimens for different HIV-1 subtypes while concurrently providing new insights on mammalian gene regulation. In studying viral factors that regulate gene expression in HIV-1, we focused attention on the HIV-1 promoter, a viral protein called Tat and a RNA hairpin called TAR. The error prone nature of HIV-1 replication has resulted in highly diverse viral sequences, and it is not clear how Tat, which plays a critical role in viral gene expression and replication, retains its complex functions. Although several important amino acid positions in Tat are conserved, we hypothesized that it may also harbor functionally important residues that may not be individually conserved yet appear as correlated pairs, and knowledge of such evolutionary information could help elucidate underlying mechanisms of Tat function. Using Information theory based approaches such as Mutual Information and protein engineering approaches, we found a pair of sites in Tat that are strongly coevolving and that provided insight into Tat-mediated viral transcription. In contrast to most coevolving protein residues that contribute to the same function, these studies showed that these two residues contribute to two mechanistically distinct steps in gene expression: binding the cellular protein, positive transcription-elongation factor b (P-TEFb) and promoting P-TEFb phosphorylation of the C-terminal domain in RNA Polymerase II (RNAPII). Moreover, Tat variants that mimic HIV-1 subtype B or C at these sites have evolved orthogonal strengths of P-TEFb binding vs. RNAPII phosphorylation, suggesting that subtypes have evolved alternate transcriptional strategies that could differentially impact latency while achieving similar gene expression levels. Interaction between Tat and the viral hairpin TAR is critical for efficient gene expression from the viral promoter and we therefore hypothesized that sequence diversity within these elements may dramatically alter the gene expression and latency properties of different subtype viruses. We found large differences in gene expression between subtypes using a variety of experimental models and showed that subtype TARs and Tats act independently to set the level of gene expression from the viral promoter. Further, using Mutual information and site-directed mutagenesis we showed that nucleotides in TAR are not coevolving with residues in Tat implying that HIV-1 has evolved a highly robust mechanism of activating gene expression in the face of rapid viral evolution. Similarly, the promoters of different HIV-1 subtypes have evolved different architectures of transcription factor binding sites (TFBS) that result in widely varying levels of gene expression and viral replication. Within this large diversity of TFBS in the HIV-1 promoter, we used in vitro models of HIV-1 latency to identify the minimal set of TFBS that contribute to most of the observed differences in gene expression and latency at steady state. In contract, we found that the dynamics of gene expression is dependent on both the minimal set of TFBS and other sites in the viral promoter. Identifying other targets within the viral promoter will provide better mechanistic understanding of the establishment and reactivation of HIV-1 latency as well as potentially identify new molecular targets to counter latency. While diversity in viral factors can contribute to differential regulation of viral gene expression, host factors can also play a significant role in this regulation. Since HIV-1 integrates semi-randomly within the human genome, another aspect of my thesis included studying the role of the cellular genomic location in regulating viral gene expression. We exploited the semi-random integration of HIV-1 to quantitatively study both how latent proviruses can be reactivated from different chromatin environments and to address a fundamental question in eukaryotic gene expression related to how the placement of a gene in the genome impacts its responsiveness to an input transcription factor signal. Using a tunable overexpression system for the transcription factor NF-[kappa]B RelA, we quantified HIV-1 expression as a function of RelA levels and chromatin features at a panel of viral integration sites. We demonstrated that chromatin environments at different genomic loci decouple transcription factor mediated gene expression induction thresholds from subsequent gene activation. We developed a functional relationship between gene expression, RelA levels, and chromatin accessibility that accurately predicted synergistic HIV-1 activation in response to combinatorial pharmacological perturbations. Thus, this quantitative study should help inform strategies for combinatorial therapies to combat latent HIV-1 and help unravel biological principles underlying selective gene expression in response to transcription factor inputs. Finally, after HIV-1 integrates into the host genome, it can either activate gene expression that leads to viral replication or become transcriptionally silent that can result in viral latency. Since stochastic fluctuations in HIV-1 gene expression are one of several factors that have been implicated in influencing this decision and thus in the establishment of viral latency, we investigated the role of the local chromatin environment in regulating gene expression noise. We showed that for clones with similar mean gene expression levels, those integrated into more heterochromatic regions are associated with wider mRNA and protein distributions. Using a two-state stochastic model of gene expression, we showed that the repressed chromatin gives rise to noisier gene expression by lowering the burst frequency. In addition to more clearly defining the role of the chromatin environment in regulating the establishment of viral latency, this study has implications for the role of chromatin in modulating transcriptional noise in eukaryotes and its evolutionary consequences in the placement of genes within the genome. Thus these studies of the role of sequence variation within the viral genome and its chromosomal integration site in regulating gene expression has resulted in better understanding of the mechanisms of gene expression and establishment of latency in HIV-1, while also helping to discern the role of chromatin in regulating mammalian gene expression.
Download or read book Encyclopedia of AIDS written by Thomas J. Hope and published by . This book was released on with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Regulation of HIV 1 Postintegration Latency by NF kappa B written by Samuel A. F. Williams and published by . This book was released on 2005 with total page 394 pages. Available in PDF, EPUB and Kindle. Book excerpt: In our initial study, we identified the phorbol ester prostratin as an inducer of latent HIV-1 gene expression in the J-Lat model of latency. We demonstrated a central role for the NF-kappaB family of transcription factors as mediators of prostratin antagonism of HIV, and for the first demonstrated recruitment of NF-kappaB RelA to the HIV-1 LTR in vivo. These studies prompted us to investigate in more detail the processes regulated by NF-kappaB that modulate expression of latent HIV-1.
Download or read book Persistent Viral Infections written by R. Ahmed and published by Wiley-Blackwell. This book was released on 1999 with total page 754 pages. Available in PDF, EPUB and Kindle. Book excerpt: Persistent Viral Infections Edited by Rafi Ahmed Emory Vaccine Center, Atlanta, USA and Irvin S. Y. Chen UCLA School of Medicine, Los Angeles, USA During the past decade much of our attention has focused on diseases associated with viral persistence. Major breakthroughs in immunology, and the advent of molecular approaches to study pathogenesis have increased our understanding of the complex virus-host interactions that occur during viral persistence. Persistent Viral Infections focuses on: * The pathogenesis and immunology of chronic infections * Animal models that provide, or have the potential to provide, major insights This volume will be essential reading for virologists, immunologists, oncologists and neurologists.
Download or read book Pocket Book of Hospital Care for Children written by World Health Organization and published by World Health Organization. This book was released on 2013 with total page 442 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Pocket Book is for use by doctors nurses and other health workers who are responsible for the care of young children at the first level referral hospitals. This second edition is based on evidence from several WHO updated and published clinical guidelines. It is for use in both inpatient and outpatient care in small hospitals with basic laboratory facilities and essential medicines. In some settings these guidelines can be used in any facilities where sick children are admitted for inpatient care. The Pocket Book is one of a series of documents and tools that support the Integrated Managem.
