Download or read book Dynamics of the HIV 1 Latent Reservoir written by Mark David Pankau and published by . This book was released on 2019 with total page 96 pages. Available in PDF, EPUB and Kindle. Book excerpt: Human immunodeficiency virus type 1 (HIV) has caused more than 35 million deaths world-wide and contributes significantly to the global burden of disease. Currently, the only effective treatment to suppress viral replication and prevent HIV transmission is combination antiretroviral therapy (ART), which prevents HIV from infecting new cells. Despite the efficacy of ART, long lived latently infected cells persist, with an estimated half-life of 44 months, and circulate throughout the infected host necessitating life-long treatment. These cells, known as the latent reservoir, contain an integrated form of the HIV genome (HIV DNA) that is transcriptionally silent, but can reactivate to produce virus. Therefore, interruption of ART inevitably leads to viral recrudescence stemming from the latent reservoir. Studying the latent reservoir is difficult because these cells contain no known biomarkers and do not always produce replication competent virus upon cellular activation. Additionally, latent reservoir cells are rare, and many proviral genomes contain defects that prevent them from producing replication competent virus. They do however confound efforts to measure the replication competent reservoir. Understanding the dynamics and correlates of reservoir seeding will be essential to develop novel cure strategies that target this latent reservoir. There is limited data on the dynamics of reservoir seeding throughout HIV infection, the impact of treatment interruption on reservoir size, and whether antibodies can play a role in limiting reservoir seeding. I focused my thesis on characterizing the seeding dynamics of latent reservoir cells containing HIV DNA (HIV DNA Reservoir) to better understand when the latent reservoir was generated and how it changed following treatment interruption. In the first part of this thesis I adapt, optimize, and validate a molecular based assay to quantitate HIV DNA from latently infected cells, as well as develop a novel cell line to detect replication competent HIV reactivated from latent reservoirs. In the second part of this thesis I demonstrate that the HIV DNA reservoir is limited by early ART and does not significantly increase following randomization to short treatment interruption in a cohort of Kenyan infants, suggesting that short treatment interruption studies may pose little risk to reservoir reseeding. I also examine the role of ADCC activity in preventing re-seeding of the latent reservoir and demonstrate that ADCC activity does not correlate with change in HIV DNA reservoir size following treatment interruption. Finally, I demonstrate that the HIV DNA reservoir is comprised mostly of viral variants circulating just prior to ART initiation, suggesting that during untreated infection the HIV DNA reservoir decays at a much faster rate than during suppressive ART. Together, these data demonstrate that the HIV DNA reservoir is limited by early ART, is not significantly reseeded with short treatment interruption, and that contrary to previous assumptions about reservoir dynamics, is decaying at a significantly faster rate pre-ART than after ART initiation, and suggest that targeting the HIV latent reservoir prior to early ART initiation may be an effective strategy to limit reservoir size, and that short treatment interruption can limit re-seeding of the latent reservoir.
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 248 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 Viral Persistence Latent Reservoir and Blips written by and published by . This book was released on 2008 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: HIV-1 eradication from infected individuals has not been achieved with the use of highly active antiretroviral therapy (HAART) for a prolonged period of time. The cellular reservoir for HIV-1 in resting memory CD4 T cells remains a major obstacle to viral elimination. The reservoir does not decay significantly over long periods of time as is able to release replication competent HIV-1 upon cell activation. Residual ongoing viral replication may likely occur in many patients because low levels of virus can be detected in plasma by sensitive assays and transient episodes of viremia, or HIV-1 blips, are often observed in patients even with successful viral suppression for many years. Here we review our current knowledge of the factors contributing to viral persistence, the latent reservoir, and blips, and mathematical models developed to explore them and their relationships. We show how mathematical modeling can help improve our understanding of HIV-1 dynamics in patients on HAART and the quantitative events underlying HIV-1 latency, reservoir stability, low-level viremic persistence, and emergence of intermittent viral blips. We also discuss treatment implications related to these studies.
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 Spatiotemporal Dynamics of HIV Infection written by Matthew Carl Strain and published by . This book was released on 2002 with total page 384 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Virus Dynamics Mathematical Principles of Immunology and Virology written by Martin Nowak and published by Oxford University Press, UK. This book was released on 2000-11-23 with total page 253 pages. Available in PDF, EPUB and Kindle. Book excerpt: This groundbreaking book describes the emerging field of theoretical immunology, in particular the use of mathematical models to describe the spread of infectious diseases within patients. It reveals fascinating insights into the dynamics of viral and other infections, and the interactions between infectious agents and immune responses. Structured around the examples of HIV/AIDS and hepatitis B, Nowak and May show how mathematical models can help researchers to understand the detailed dynamics of infection and the effects of antiviral therapy. Models are developed to describe the dynamics of drug resistance, immune responses, viral evolution and mutation, and to optimise the design of therapy and vaccines. - ;We know, down to the tiniest details, the molecular structure of the human immunodeficiency virus (HIV). Yet despite this tremendous accomplishment, and despite other remarkable advances in our understanding of individual viruses and cells of the immune system, we still have no agreed understanding of the ultimate course and variability of the pathogenesis of AIDS. Gaps in our understanding like these impede our efforts towards developing effective therapies and preventive vaccines. Martin Nowak and Robert M May describe the emerging field of theoretical immunology in this accessible and well- written text. Using mathematical modelling techniques, the authors set out their ideas about how populations of viruses and populations of immune system cells may interact in various circumstances, and how infectious diseases spread within patients. They explain how this approach to understanding infectious diseases can reveal insights into the dynamics of viral and other infections, and the interactions between infectious agents and immune responses. The book is structured around the examples of HIV/AIDS and Hepatitis B virus, although the approaches described will be more widely applicable. The authors use mathematical tools to uncover the detailed dynamics of the infection and the effects of antiviral therapy. Models are developed to describe the emergence of drug resistance, and the dynamics of immune responses, viral evolution, and mutation. The practical implications of this work for optimisation of the design of therapy and vaccines are discussed. The book concludes with a glance towards the future of this fascinating, and potentially highly useful, field of study. - ;... an excellent introduction to a field that has the potential to advance substantially our understanding of the complex interplay between virus and host - Nature
Download or read book Mathematical Computational and Experimental T Cell Immunology written by Carmen Molina-París and published by Springer Nature. This book was released on 2021-01-04 with total page 300 pages. Available in PDF, EPUB and Kindle. Book excerpt: Mathematical, statistical, and computational methods enable multi-disciplinary approaches that catalyse discovery. Together with experimental methods, they identify key hypotheses, define measurable observables and reconcile disparate results. This volume collects a representative sample of studies in T cell immunology that illustrate the benefits of modelling-experimental collaborations and which have proven valuable or even ground-breaking. Studies include thymic selection, T cell repertoire diversity, T cell homeostasis in health and disease, T cell-mediated immune responses, T cell memory, T cell signalling and analysis of flow cytometry data sets. Contributing authors are leading scientists in the area of experimental, computational, and mathematical immunology. Each chapter includes state-of-the-art and pedagogical content, making this book accessible to readers with limited experience in T cell immunology and/or mathematical and computational modelling.
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 Disease Control Priorities Third Edition Volume 6 written by King K. Holmes and published by World Bank Publications. This book was released on 2017-11-06 with total page 1027 pages. Available in PDF, EPUB and Kindle. Book excerpt: Infectious diseases are the leading cause of death globally, particularly among children and young adults. The spread of new pathogens and the threat of antimicrobial resistance pose particular challenges in combating these diseases. Major Infectious Diseases identifies feasible, cost-effective packages of interventions and strategies across delivery platforms to prevent and treat HIV/AIDS, other sexually transmitted infections, tuberculosis, malaria, adult febrile illness, viral hepatitis, and neglected tropical diseases. The volume emphasizes the need to effectively address emerging antimicrobial resistance, strengthen health systems, and increase access to care. The attainable goals are to reduce incidence, develop innovative approaches, and optimize existing tools in resource-constrained settings.
Download or read book Rebound Relationships written by D. Brenda Salantes and published by . This book was released on 2018 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: In HIV-infected patients, combination antiretroviral therapy (cART) during HIV-1 infection potently suppresses viral replication and slows progression to AIDS. Upon cessation of cART, however, systemic infection is rapidly re-established due to the long-lived pool of latently infected cells, or HIV reservoir, that is seeded early in infection and persists despite years of cART in patients. This long-lived reservoir is the target of novel curative strategies. In order to determine in vivo efficacy of these interventions, closely monitored analytical treatment interruption (ATI) is required. Previously conducted ATI trials have provided important baseline information regarding the kinetics and diversity of viruses emerging from latency. As future HIV curative clinical trials move towards prolonged periods of ATI, studies assessing the effect of ATI on host virus-immune dynamics will provide an important baseline that will further our understanding of trial outcomes. In this thesis, I conducted single genome sequencing (SGS) of HIV-1 env and neutralization assays using autologous antibodies to characterize the viral and immune dynamics of rebound in two clinical trials: a longitudinal ATI study in the absence of any intervention, and a brief ATI study involving administration of the broadly neutralizing antibody VRC01. Our data, consistent with previous studies, demonstrated that viral rebound occurs within four weeks of ATI and is established by multiple latently infected cells in the majority of HIV-infected participants. Analyses of plasma containing VRC01 and/or autologous antibodies show that latent reservoir viruses can experience an antibody-mediated neutralization sieve effect, thus preventing the persistence of antibody-sensitive viruses. Additionally, SGS of latent viruses before and after brief ATI show that the size and composition of the peripheral latent viral reservoir is not significantly altered during ATI, demonstrating that short-term ATI is safe. Taken together, these data highlight the complex virus-host dynamics during ATI, and further suggest that passively infused or host-derived neutralizing antibodies can exert selective pressure, altering the evolution of HIV in its host.
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 Handbook on Immunosenescence written by Tamas Fulop and published by Springer Science & Business Media. This book was released on 2009-02-27 with total page 1693 pages. Available in PDF, EPUB and Kindle. Book excerpt: This authoritative handbook covers all aspects of immunosenescence, with contributions from experts in the research and clinical areas. It examines methods and models for studying immunosenescence; genetics; mechanisms including receptors and signal transduction; clinical relevance in disease states including infections, autoimmunity, cancer, metabolic syndrome, neurodegenerative diseases, frailty and osteoporosis; and much more.
Download or read book Immunopathogenesis of HIV Infection written by Anthony S. Fauci and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 159 pages. Available in PDF, EPUB and Kindle. Book excerpt: During the last 5 years, major advances have been made in our understanding of the pathogenesis of human immunodeficiency virus (HIV) disease and in the development of new potent antiviral agents. With regard to HIV pathogenesis, several recent observations have not only changed our perspectives of HIV disease, but have been critical for the design of therapeutic strategies.
Download or read book The Evolution of HIV written by Keith A. Crandall and published by JHU Press. This book was released on 1999-04-26 with total page 524 pages. Available in PDF, EPUB and Kindle. Book excerpt: Wolinsky.-- "European Molecular Biology Organization Reports"
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 Infectious Disease Epidemiology written by Ibrahim Abubakar and published by Oxford University Press. This book was released on 2016-04-07 with total page 295 pages. Available in PDF, EPUB and Kindle. Book excerpt: Infectious Disease Epidemiology is a concise reference guide which provides trainees and practicing epidemiologists with the information that they need to understand the basic concepts necessary for working in this specialist area. Divided into two sections, part one comprehensively covers the basic principles and methods relevant to the study of infectious disease epidemiology. It is organised in order of increasing complexity, ranging from a general introduction to subjects such as mathematical modelling and sero-epidemiology. Part two examines key major infectious diseases that are of global significance. Grouped by their route of transmission for ease of reference, they include diseases that present a particular burden or a high potential for causing mortality. This practical guide will be essential reading for postgraduate students in infectious disease epidemiology, health protection trainees, and practicing epidemiologists.
Download or read book Hybrid Approach to Predict Resting CD4 T cell Reservoirs of HIV 1 written by and published by . This book was released on 2019 with total page 42 pages. Available in PDF, EPUB and Kindle. Book excerpt: Human immunodeficiency virus (HIV) is a retrovirus that compromises a person’s immune system by diminishing the number of CD4+ T-cells available to fight foreign bodies. Despite successes of antiretroviral therapies on suppressing the viral load in HIV patients, these treatments are unable to eradicate the virus. The primary obstacle to HIV eradication is resting CD4+ T-cell reservoirs, which may remain dormant for a long time and often cause viral rebounds after treatment cessation. Many mathematical models have been proposed to explore the behavior of the latent reservoir but much remains uncertain on the accurate prediction of the frequency of latently infected cells, mainly because of limited data due to complexity of measuring such cells. In this thesis, we develop a hybrid approach with mathematical modeling and machine learning combined to predict the frequency of resting CD4+ T-cell infection (RCI) reservoirs. Our framework takes advantage of the insights obtained from mathematical modeling to generate large number of reliable data sets that are then used in machine learning applications to predict latently infected cells. We found that the predictions based on our framework are consistent with the experimental data. We identified that the RCI frequency measurements with the lag time of four months can better predict the RCI frequency. Such information can be helpful for medical examiners in determining a reasonable interval between measurements of RCI frequency. Our hybrid approach can be widely applicable to many other cases in which the data is limited due to the requirement of a stringent assay for their measurement.
