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 Exploring Novel Approaches to Eliminate HIV Reservoirs to Achieve a Cure for HIV written by Renee Marije Van Der Sluis and published by Frontiers Media SA. This book was released on 2021-04-07 with total page 111 pages. Available in PDF, EPUB and Kindle. Book excerpt:
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 Recent Progress in HIV Research written by Anabella Frost and published by Hayle Medical. This book was released on 2023-09-19 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: HIV is a virus that severely affects the immune system resulting in acquired immunodeficiency syndrome (AIDS). The treatment of HIV involves combination antiretroviral therapy (cART). This therapy suppresses HIV-1 replication, blocks transmission, and improves immune responses. cART is a lifelong treatment, and does not eliminate the virus while also having side effects. The focus in the treatment of HIV is the reactivation of HIV reservoirs for subsequent termination by viral cytopathic effects or host immunity. The most researched HIV reservoir is resting memory CD4+ T cells in peripheral blood and lymphoid tissues. The antiretroviral therapies have expanded significantly in the recent times and comprise five categories of antiretrovirals, including nucleoside reverse transcriptase inhibitors (NRTIs), protease inhibitors, non-nucleoside reverse transcriptase inhibitors (NNRTIs), integrase strand transfer inhibitors (INSTIs) and entry inhibitors. This book unfolds the innovative aspects of HIV research which will be crucial for the progress of this field in the future. For someone with an interest and eye for detail, this book covers the most significant topics on HIV-AIDS and its treatment.
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 Lymph Node T Cell Dynamics and Novel Strategies for HIV Cure written by Constantinos Petrovas and published by Frontiers Media SA. This book was released on 2019-02-11 with total page 186 pages. Available in PDF, EPUB and Kindle. Book excerpt: Currently, more than 36 million people are infected with HIV. Although the introduction of highly active anti-retroviral therapy (HAART) has led to substantial advances in the clinical management of HIV infected individuals, HAART cannot completely eliminate the virus. This is because CD4 T helper cells, harboring the virus, remain dormant reservoirs. These reservoirs are difficult to measure and are present even in HAART-treated HIV infected individuals with undetectable levels of HIV in the blood. A growing body of studies has revealed follicular helper (Tfh) CD4 T cells, a highly differentiated CD4 T cell population localized in immunologically sanctuary sites (follicle/germinal center), as a major reservoir of HIV. The present Frontiers in Immunology eBook compiles 16 timely review articles focusing on the dynamics of major follicular immune cell types in HIV/SIV infection and their potential role for disease pathogenesis and the viral persistence in the lymph node. This eBook provides a comprehensive presentation of recent published work on lymph node and especially Tfh cell dynamics in HIV infection and we hope that it will be useful for our further understanding of how such dynamics affect the interplay between virus and host as well as for the discovery of novel therapeutic targets in the fight against HIV.
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 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 The Role of Viral Reservoirs in HIV 1 Infection written by Daniel Donahue and published by . This book was released on 2013 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: "The major source of virus production during human immunodeficiency virus type 1 (HIV-1) infection is activated CD4 T-cells, although infection of some other cell types can also contribute to virus production. A viral reservoir is either a cell type or an anatomical site whose properties can result in the persistence of infectious virus for a longer time period than the primary source of virus production, and several different HIV-1 reservoirs are known to exist. The work presented in this thesis examines three different aspects of viral reservoirs in HIV-1 infection. The first part (Chapter 2) is an investigation of the role of long-lived virus-producing cells during antiretroviral therapy. Specifically, cell culture experiments were designed that have resulted in a further understanding of the inhibition of HIV-1 replication in viral reservoirs. The second and third parts of this thesis (Chapters 3 and 4) consider the role of latently infected CD4 T-cells in HIV-1 infection. Latently infected cells carry an HIV-1 genome that is integrated into the cellular chromatin and does not produce viruses, but that retains the capacity for infectious virus production in the future. These cells form the latent reservoir, which represents the major barrier to an HIV-1 cure and necessitates life-long antiretroviral therapy for infected individuals. The work presented in Chapter 3 demonstrates that it is possible to inhibit the establishment of latent infection in vitro, something that has not yet been achieved clinically. Chapter 4 considers the potential contribution of latent viruses to viral genetic diversity, and shows that latent viruses can contribute to the development of multidrug resistance. In summary, the work presented in this thesis provides for a greater understanding of the role of viral reservoirs in HIV-1 infection and of the ability of antiretroviral drugs to combat infection." --
Download or read book Frontiers in Clinical Drug Research HIV Volume 5 written by Atta-ur-Rahman and published by Bentham Science Publishers. This book was released on 2021-10-04 with total page 222 pages. Available in PDF, EPUB and Kindle. Book excerpt: Frontiers in Clinical Drug Research – HIV is a book series that brings updated reviews to readers interested in learning about advances in the development of pharmaceutical agents for the treatment of acquired immune deficiency syndrome (AIDS) and other disorders associated with human immunodeficiency virus (HIV) infection. The scope of the book series covers a range of topics including the medicinal chemistry and pharmacology of natural and synthetic drugs employed in the treatment of AIDS (including HAART) and resulting complications, and the virology and immunological study of HIV and related viruses. Frontiers in Clinical Drug Research – HIV is a valuable resource for pharmaceutical scientists, clinicians and postgraduate students seeking updated and critically important information for developing clinical trials and devising research plans in HIV/AIDS research. The fifth volume of this series features 5 chapters that cover these topics: - Clinical Eradication of Latent HIV Reservoirs: Where Are We Now? - HIV-1 Genotypic Drug Resistance Testing and Next-Generation Sequencing - Current and Promising Multiclass Drug Regimens and Long-Acting Formulation Drugs in HIV Therapy - Role of Nanotechnology in HIV Diagnosis and Prognosis - Preventive and Therapeutic Features of Combination Therapy for HIV.
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 Persistence of HIV 1 and SIV Viral Reservoirs in Gut associated Lymphoid Tissue written by Paula Lerner and published by . This book was released on 2011 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Gut Associated Lymphoid Tissue (GALT) is the largest lymphoid organ in the body, as well as an important site for early viral replication and substantial depletion of memory CD4+ T-cells in human immunodeficiency virus-1 (HIV-1) infection. Highly active antiretroviral therapy (HAART) effectively suppresses HIV replication and restores CD4+ T-cell numbers in the peripheral blood of HIV infected patients, yet, patients on HAART display slow and incomplete restoration of CD4+ T cells in GALT. Information about the persistence of HIV reservoirs and their evolution in GALT is limited. My research project for the Ph.D. focused on the investigation of the establishment of HIV reservoirs in GALT during the initial stages of HIV infection and their evolution during therapy or therapy interruption. We utilized the simian immunodeficiency virus infected rhesus macaque model of AIDS to investigate the establishment and compartmentalization of viral reservoirs in the CD4+ T cells from GALT, lymph nodes and peripheral blood during the course of viral infection as well as during therapy. We investigated HIV reservoirs in GALT and PBMC and their impact on the gut mucosal immune system from three HIV-infected patients who initiated HAART during primary HIV infection and opted to interrupt HAART by phylogenetic analysis of viral variants, flow cytometric analysis of changes in T- cell homeostasis and DNA microarray analysis of altered gene expression profiles of the molecular processes. A rapid increase in plasma viral loads with a modest decline in peripheral blood CD4+ T-cells was observed following HAART interruption. However, severe loss of mucosal CD4+ T-cells occurred. This was accompanied by increased mucosal gene expression regulating IFN mediated antiviral responses and immune activation; a profile similar to those found in HAART-naïve chronically HIV infected patients. Longitudinal HIV sequence analysis revealed that proviral variants in GALT and PBMC exhibited low levels of genomic diversity and not much divergence throughout the infection, even after therapy interruption. An unchanged population of infected cells persisted in GALT months after HAART interruption. Sequence analysis of rebound virus suggested that GALT was not the major contributor to the post-interruption plasma viremia nor were GALT HIV reservoirs rapidly replaced by HIV rebound variants, at least 9-12 months after therapy interruption. In a comparative study, we utilized the SIV model to study compartmentalization of viral populations in CD4+ T-cells from GALT, lymph nodes and peripheral blood during therapy. Data on viral load profiles in plasma and tissues, phylogenetic analyses and quantitative measurements of viral population structure suggested that residual viral replication persisted in GALT during therapy. Secondly, compartmentalization of proviral populations between GALT and other lymphoid tissues was observed. However, limited exchange of variants between GALT and peripheral sites over time was evident. Based on gene flow analysis of tissue and peripheral blood compartments, residual plasma RNA during antiretroviral therapy seemed to originate from GALT and lymph nodes as well as the peripheral blood. Our data supports a model of early establishment of stable viral reservoirs in the GALT. Our findings suggest that early detection and treatment of HIV and SIV infection might be beneficial in controlling viral evolution and limiting establishment of diverse viral reservoirs.
Download or read book HIV Cure Through Eradication of Viral Reservoirs written by Maher M. Elsheikh and published by . This book was released on 2018 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Persistence of the latent HIV reservoir is the main obstacle in preventing or curing HIV. Even though a combination of antiretroviral therapy (cART) is effective in controlling the virus by suppressing its replication and infectivity to below detection levels, cART cannot eliminate the latent reservoir, and must be taken for life. After encountering HIV, some infected CD4+ T cells revert to a resting state and persist as memory T cells that remain quiescent while containing the stable HIV proviral DNA (latent reservoir). With a stable and long-lived reservoir, HIV remains a global health problem because the proviral DNA is transcriptionally silent but is capable of producing infectious particles when cART is interrupted. According to WHO, more than 34 million people died due to AIDS over the past three decades, and about 37 million are currently living with it. In addition, there are approximately two million new cases each year. HIV-infected individuals do not achieve complete immunologic reconstitution because viral suppression is incomplete, and immune activation occurs chronically. The inability of cART to eradicate HIV from latent viral reservoirs necessitates the development of novel therapeutic approaches to eradicate the virus from infected individuals so that cART can be discontinued. The goal of this work was to investigate innovative experimental approaches to eradicate the latent HIV reservoir by targeting specific molecular mechanisms within the PKC/NF-kB and p-TEFb signaling pathways of HIV-infected resting memory CD4+ T cells involved in viral replication and silencing during the HIV life cycle. This goal was successfully achieved by implementing two independent experimental approaches: 1) Eliminating HIV infected cells by inducing reactivation of latent HIV and targeting the activated cells for apoptosis (sterilizing cure). 2) Inducing permanent silencing of HIV in the latent viral reservoir by shutting down the HIV replication machinery, which could permanently inhibit viral replication in the infected cells (functional cure). Subsequently, we were able to identify latency reactivating agents and apoptosis inducing agents that, when used in combination, dramatically reduced the latent HIV reservoir. We were also able to identify several viral silencing agents (VSA) that target essential cellular and viral proteins within the NF-[kappa]B and PKC signaling pathways in infected cells. These VSAs curtail HIV proviral transcription and elongation, which permanently silence latent HIV for multi-generations. They were also effective in reducing viral transcription. Although our data demonstrated that this combination treatment has great potential as an effective anti-HIV therapy, additional testing using larger sample sizes and multiple latency cell models that target various cell reservoirs is needed in order to demonstrate that this therapy is effective and fully functional against various viral sanctuaries in the human body, and is capable of completely eliminating the reservoir with minimal cytotoxicity. Nevertheless, this was an important initial step to prove that our proposed strategy can be successful and should be evaluated further. This novel treatment strategy has the possibility of eliminating the latent HIV reservoir to achieve a drug-free remission and to cure HIV in the future.
Download or read book Human Virology written by John Sidney Oxford and published by Oxford University Press. This book was released on 2016 with total page 365 pages. Available in PDF, EPUB and Kindle. Book excerpt: Written by leading authors in the field with both clinical and molecular expertise, Human Virology provides an accessible introduction to this fascinating and important field, making the text ideal for students encountering virology for the first time.
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 Targeting HIV Reservoirs and Reconstituting the Immune System written by Research Institute for Genetics and Human Therapy and published by . This book was released on 1999 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Eradication of the Latent HIV Viral Reservoir written by Nixon Niyonzima and published by . This book was released on 2016 with total page 126 pages. Available in PDF, EPUB and Kindle. Book excerpt: The major barrier to HIV cure is the establishment of a long-lived latent viral reservoir that is not affected by combination ant-retroviral therapy and is not cleared by the immune system. When HIV positive patients on combination anti-retroviral therapy with undetectable viremia interrupt therapy, viremic rebound occurs within two weeks of discontinuing cART. This viral rebound is due to stochastic reactivation of HIV transcription and replication in the long-lived viral reservoir. HIV cure necessitates eradication of this long-lived reservoir. To eradicate the HIV proviral reservoir, we are using HIV-specific engineered meganucleases. Mutations in essential HIV genes can disrupt the integrated provirus and could prevent reactivation from latency. I demonstrate that engineered meganucleases can introduce mutations in an integrated HIV provirus. The HIV-specific engineered meganucleases also cleave and introduce mutations in genomic off-target sites. We show that a second generation of an HIV-specific meganuclease developed using structure guided protein engineering, has an improved off-target toxicity profile and retains activity at the HIV target site. I further demonstrate that expression of the three prime repair exonuclease-2 (Trex2) in combination with either the meganuclease or fusion megaTALs increases the frequency of mutations at the HIV target site. The compact size of meganucleases and the increasing ease with which they can be redesigned to recognize new DNA sequences makes meganucleases an attractive tool for HIV cure applications. HIV cure also requires precise quantitation of the viral reservoir. Current assays used to measure the HIV viral reservoir are imprecise and tend to either over or underestimate the size of the functional reservoir. In the setting of both structured and analytical treatment interruptions it is critical that the reservoir is measured accurately so that patients do not discontinue cART in the setting of large functional reservoirs. I describe here a multiplex ddPCR assay that can simultaneously detect up to six viral genes in the same reaction. The multiplex ddPCR assay gives an estimate of the completeness of the integrated provirus, which can be used to measure levels of functional integrated HIV provirus. I hypothesize that this multiplex ddPCR assay gives a truer estimate of the size of the functional HIV reservoir.
