[PDF] Hiv Induced Cellular Reprogramming eBook

Author : Brian Patrick Fury
Publisher :
Page : 798 pages
File Size : 25,54 MB
Release : 2011
Category :
ISBN :

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Human immunodeficiency virus continues to persist in millions of people worldwide. While antiretroviral drug therapies have improved life for many, a cure remains elusive. Long-term antiretroviral drug therapy can also lead to toxicity, the development of drug resistant strains and the persistence and maintenance of latent reservoirs in resting cluster of differentiation 4 positive T-lymphocytes. Gene therapy offers a promising alternative strategy for eradicating human immunodeficiency virus infection through the development of lentiviral vectors comprised of highly potent anti-HIV transgenes capable of inhibiting human immunodeficiency virus infection during the preintegration phases. Cellular reprogramming allows for the generation of induced pluripotent stem cells (iPSC) that are similar to embryonic stem cell-like cells with the potential to differentiate into any cell type in the body. In this study, hematopoietic stem cells were isolated from umbilical cord blood, transduced with a triple combination lentiviral vector containing three potent anti-HIV transgenes encoding a chemokine-chemokine receptor 5 short hairpin RNA, a chimeric tripartite motif-containing protein 5, and a viral transactivation response element decoy. These cells were then de-differentiated back into an undifferentiated pluripotential state by transduction with specific transcription factors octamer-binding transcription factor 4 (OCT4), sex determining region Y-box 2 (SOX2), cytoplasmic c-MYC, and Krüppel-like factor 4 (KLF4). The resulting colonies were analyzed and found to express the anti-HIV genes, by enhanced green fluorescent protein detection. Additionally, the pluripotency markers were also determined to be expressed indicating successful transduction and reprogramming. Reprogramming patient-specific cells to derive personalized iPSCs is an excellent source for potentially transplantable tissue that will not cause an immune response and subsequent rejection. This could be used to treat a myriad of human blood and degenerative diseases without the ethical concerns attached to the acquisition and use of ES cells. In addition, this iPSC approach could provide a highly beneficial and personalized patient specific platform for future treatments while diminishing the need to rely on potentially toxic drug therapies and resistant strains.

Author : Craig Meyers
Publisher : Springer
Page : 250 pages
File Size : 49,75 MB
Release : 2018-12-06
Category : Medical
ISBN : 3030035026

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One of the most important aspects of AIDS is the loss of protective immune function in the infected host which leads to increased prevalence of opportunistic infections and cancers. This book specifically addresses viral-induced human cancers associated with AIDS and observed in the AIDS population. It addresses the specific treatment required in this special population and the molecular biology of the causative viral agents.

Author : Charles Nathan S. Allen
Publisher :
Page : 242 pages
File Size : 31,49 MB
Release : 2021
Category :
ISBN :

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A significant number of patients infected with HIV-1 suffer from HIV-associated neurocognitive disorders (HAND) such as spatial memory impairments and learning disabilities (SMI-LD). SMI-LD is also observed in patients using combination antiretroviral therapy (cART). Our lab has demonstrated that the HIV-1 protein, gp120, promotes SMI-LD by altering mitochondrial functions and energy production. However, the exact mechanisms that causes these changes that are observed to lead to memory dysfunction have yet to be elucidated. We have investigated cellular processes upstream of the mitochondrial functions and discovered that gp120 causes metabolic reprogramming. Effectively, we have shown that gp120 decreases mitochondrial oxygen consumption rate (OCR) and increases the expression of polypyrimidine tract binding protein 1 (PTBP1), resulting in the alternative splicing of pyruvate kinase M (PKM) from PKM1 to PKM2. We have also shown that these events lead to the accumulation of advanced glycation end products (AGEs) and prevent the cleavage of pro-brain-derived neurotrophic factor (pro-BDNF) protein into mature BDNF. The accumulation of proBDNF results in signaling that increases the expression of the inducible cAMP early repressor (ICER) protein which then occupies the cAMP response element (CRE)-binding sites within promoter regions. One of the more important promoters that ICER binds to is the BDNF promoters II and IV, thus altering normal synaptic plasticity. We also validated these results in an animal model. We have also shown that with the addition of a therapeutic drug, Tepp-46, which promotes PKM2 tetramers, the metaboliciv changes in glycolysis and subsequential accumulation of AGEs can be reversed. Therefore, we concluded that gp120 reprograms cellular metabolism, causing changes linked to disrupted memory in HIV-infected patients, as well as a possible therapeutic target to aid in the prevention of metabolic reprogramming and the progression of HAND.

Author : Guido Silvestri
Publisher : Springer
Page : 253 pages
File Size : 12,24 MB
Release : 2018-10-11
Category : Medical
ISBN : 303002816X

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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 : King K. Holmes
Publisher : World Bank Publications
Page : 1027 pages
File Size : 44,46 MB
Release : 2017-11-06
Category : Medical
ISBN : 1464805253

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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.

Author : M. Brennan-Ing
Publisher : Karger Medical and Scientific Publishers
Page : 256 pages
File Size : 46,98 MB
Release : 2016-11-22
Category : Psychology
ISBN : 3318059463

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Despite decades of attention on building a global HIV research and programming agenda, HIV in older populations has generally been neglected until recently. This new book focuses on HIV and aging in the context of ageism with regard to prevention, treatment guidelines, funding, and the engagement of communities and health and social service organizations. The lack of perceived HIV risk in late adulthood among older people themselves, as well on the part of providers and society in general, has led to a lack of investment in education, testing, and programmatic responses. Ageism perpetuates the invisibility of older adults and, in turn, renders current medical and social service systems unprepared to respond to patients’ needs. While ageism may lead to some advantages – discounts for services, for example – it is the negative aspects that must be addressed when determining the appropriate community-level response to the epidemic.

Author : Craig Meyers
Publisher : Springer Science & Business Media
Page : 274 pages
File Size : 45,53 MB
Release : 2007-05-04
Category : Medical
ISBN : 0387468161

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One of the most important aspects of AIDS is the loss of protective immune function in the infected host which leads to increased prevalence of opportunistic infections and cancers. This book specifically addresses viral-induced human cancers associated with AIDS and observed in the AIDS population. It addresses the specific treatment required in this special population and the molecular biology of the causative viral agents.

Author : R. Ahmed
Publisher : Wiley-Blackwell
Page : 754 pages
File Size : 28,96 MB
Release : 1999
Category : Medical
ISBN :

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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.