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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.
The study of antiviral drug resistance has provided important insights into the structure of virus enzymes, the functions of certain genes, mechanisms of action of antiviral drugs, the design of new antiviral compounds and the pathogenesis of viral diseases. The emergence of resistant strains must be explored at all stages of drug development: during the preclinical evaluation of candidate compounds; during the early clinical evaluation of new drugs; and as part of epidemiological surveillance for the prevalence of resistance during use of approved treatments. Accumulating understanding of antiviral drug resistance thus reflects progress in the chemotherapy of viral infection. Antiviral Drug Resistance provides state-of-the-art coverage of the basic and clinical aspects of this subject. It deals with the basic science, including the mechanisms of drug resistance and drug action, genetics of drug resistance, cross resistance, and X-ray crystallographic structural aspects of resistance, as well as the clinical aspects, including issues of assay of susceptibility of clinical isolates, descriptive aspects of emergence of reduced susceptibility, and clinical significance and impact of resistance. As such this unique volume will be essential to basic researchers in drug discovery and viral pathogenesis, as well as clinicians involved in antiviral chemotherapy.
The world has recorded losses in terms of human life as well as extensive time spent in experimentation with development of new drugs, elucidation of disease mechanism(s), and therapeutic agent discovery. Ethical and legal issues cojoin in slowing down scientific discoveries in medicine and biology. The past two (2) decades, therefore, have seen tremendous attempts that largely are successful in developing animal models with the characteristics of mimicking, approximating, or expressing transplanted human organs/tissues. These models or rather approaches seem to be fast, cost-effective, and easy to maintain compared to primates. This book is a collection of expert essays on animal models of human diseases of global interest. A visible objective of the book is to provide real-time experimental approach to scientists, clinicians, ethicists, medicolegal/medical jurisprudence workers, immunologists, postgraduate students, and vaccinologists and informative and multidisciplinary approach for the identification of new therapeutic targets and biomarkers using animal models as well as investigating the pathogenesis and therapeutic strategies of human diseases. An increased understanding of the genetic, molecular, and cellular mechanisms responsible for the development of human diseases has laid out the foundation for the development of rational therapies mainly with animal models.
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.
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.
Dr. Joshua Lederberg - scientist, Nobel laureate, visionary thinker, and friend of the Forum on Microbial Threats - died on February 2, 2008. It was in his honor that the Institute of Medicine's Forum on Microbial Threats convened a public workshop on May 20-21, 2008, to examine Dr. Lederberg's scientific and policy contributions to the marketplace of ideas in the life sciences, medicine, and public policy. The resulting workshop summary, Microbial Evolution and Co-Adaptation, demonstrates the extent to which conceptual and technological developments have, within a few short years, advanced our collective understanding of the microbiome, microbial genetics, microbial communities, and microbe-host-environment interactions.
Infection with the human immunodeficiency virus is characterized by the destruction of the host immune system as also reflected by a progressive loss of CD4-positive T-cells. This finally results in the host's incapacity to deal with opportunistic infections and the immune surveillance of tumors, a clinical status known as the Acquired Immunodeficiency Syndrome (AIDS). The book AIDS Pathogenesis provides the reader with a complete overview of the clinical course of HIV-1 infection. It describes the clinical aspects of primary infection, the different clinical outcomes of HIV-1 infection, and strategies for anti-viral treatment. In addition, more fundamental aspects of HIV-1 infection are reviewed. These include the biology of the virus and the novel insights in AIDS pathogenesis. Not only is the significance of an HIV-specific cellular and humoral immune response discussed, but also the possible incapacity of the adult human host to deal with T-cell destruction. Finally, the book discusses the currently used laboratory markers that allow for monitoring of the clinical course of infection.
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.
Cell Biology and Immunology of Leukocyte Function is a collection of papers presented at the 12th International Leukocyte Culture Conference, held in Beersheba, Israel on June 1978. This book is organized into seven parts encompassing 111 chapters. The contributors cover the different aspects of cell biology and immunology and the unique leukocyte function. Part I describes the mechanism of lymphocyte activation, the structure and function of the plasma membrane, and the macromolecular synthesis during lymphocyte activation. This part also deals with the interaction of lymphocytes with mitogenic lectins, the comparison of the mitogenic and nonmitogenic lectin binding, and the role of macrophages in the response of lymphocytes to lectins. Part II explores the thymic factors and the development of characteristic markers, antigens, and receptors. This part particularly emphasizes lymphocyte differentiation. Parts III and IV examine the genetic control and intercellular interactions involved in leukocyte function and the parameters of the immune response under in vitro conditions. Chapters on cytotoxicity, the mechanisms of phagocytic killing, autoimmunity, and the responses of leukocytes to tumor cells are included in these parts. Part V discusses the interactions of viruses and leukocytes and provides data on the physical mapping and analysis of sarcoma and leukemia viruses, while Part VI considers the application of leukocyte culture to problems of clinical medicine. Part VII involves the study of radiation effects, with an emphasis on the application of total lymphoid irradiation to the induction of transplantation tolerance. This part also looks into the role of the DNA repair process. Cell biologists, immunologists, and biomedical scientists and researchers will greatly benefit from this book.