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 first book to specifically cover the molecular biology of retroviruses - of immense importance since the high profile of HIV. International contributors provide detailed reviews of the latest knowledge. An excellent text for both medical and non-medical researchers, it also serves as an illuminating introduction for scientists active in other areas.
This book provides a review of the multitude of nucleic acid polymerases, including DNA and RNA polymerases from Archea, Bacteria and Eukaryota, mitochondrial and viral polymerases, and other specialized polymerases such as telomerase, template-independent terminal nucleotidyl transferase and RNA self-replication ribozyme. Although many books cover several different types of polymerases, no book so far has attempted to catalog all nucleic acid polymerases. The goal of this book is to be the top reference work for postgraduate students, postdocs, and principle investigators who study polymerases of all varieties. In other words, this book is for polymerase fans by polymerase fans. Nucleic acid polymerases play a fundamental role in genome replication, maintenance, gene expression and regulation. Throughout evolution these enzymes have been pivotal in transforming life towards RNA self-replicating systems as well as into more stable DNA genomes. These enzymes are generally extremely efficient and accurate in RNA transcription and DNA replication and share common kinetic and structural features. How catalysis can be so amazingly fast without loss of specificity is a question that has intrigued researchers for over 60 years. Certain specialized polymerases that play a critical role in cellular metabolism are used for diverse biotechnological applications and are therefore an essential tool for research.
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.
A magisterial survey of all aspects of the reverse transcriptase inhibitors (RTIs) used to treat HIV/AIDS, including drug discovery, pharmacology, development of drug resistance, toxicity, and prevention of mother-to-child transmission of HIV/AIDS. The authors synthesize our current understanding of the role of reverse transcriptase in the viral life cycle, describe the discovery and development of eight nucleoside and nucleotide analogs that represent milestones in treatment history, and thoroughly discuss the question of toxicity and resistance to this class of drugs. They also address three non-nucleoside RTIs and their pharmacokinetics and comparative clinical efficacy, new RTIs currently under development, and the impact of approved agents on treatment, in general, and on vertical transmission in the developing world.
"Human Retroviruses: Methods and Protocols collects key experimental protocols that have provided the basis of the major discoveries of the field. Split into five sections, this detailed volume covers mapping of the HIV life cycle, isolation, co-receptor use, and cell tropism of HIV-1, in vivo quantification of HIV-1, biological aspects of HIV-1, as well as HTLVs. Some articles explore assay and function of accessory genes, largely involving the interface between retroviral and host factors, the extracellular role of Tat and Tax, resembling the function of cytokines, and the biotechnological exploitation of HIV as lentiviral vector to carry foreign genes with therapeutic value. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Comprehensive and authoritative, Human Retroviruses: Methods and Protocols provides state-of-art methodological protocols from world leaders in human retrovirology, essential for any lab working this vital field."--Publisher's description.
The past few years have witnessed an explosive increase in our collective knowledge of the biology of the human immunodeficiency virus (HIV). Researchers have acquired new understanding of the virus's biochemistry, molecular biology, pathogenesis, genetics, and immunobiology. Resulting therapeutic advances have significantly prolonged the lives of thousands. Yet, the need to develop better therapies is ever more acute and--given the virus's continued spread through the human population--the need for an effective vaccine is urgent. These goals can be accomplished only through the experienced synthesis of information from the many disciplines participating in HIV research and through the insights of new investigators. This volume is designed to lower the barriers imposed on investigators by the sheer volume of available information--information that often can be found only in far-flung and specialized journals. It provides, in a single resource, an in-depth overview of the diverse areas that constitute HIV research. The result is a broad introduction for students and researchers new to the field as well as an integrated overview for researchers specialized in particular areas of HIV investigation. The volume will also benefit those seeking technical understanding of the virus's biology, including physicians treating HIV-infected patients. Each chapter is a comprehensive presentation of one area of current AIDS research--including work on the virus life cycle, epidemiology, genetics, protease and reverse transcriptase inhibitors, receptor and co-receptor interactions, therapeutic targets, clinical treatment, immunobiology, and vaccines--written by a leading researcher in that area. The contributors are Jon P. Anderson, Jan Balzarini, Elana Cherry, Thomas J. Coates, Chris Collins, Jon H. Condra, Mark B. Feinberg, Richard B. Gaynor, Matthias Götte, Daria J. Hazuda, Spyros Kalams, Nathaniel R. Landau, Gerald H. Learn, Norman L. Letvin, James I. Mullins, Willscott E. Naugler, David Nickle, Matthew Rain, Allen G. Rodrigo, Daniel Shriner, Shalom Spira, Mario Stevenson, Todd Summers, Catherine Ulich, Joseph P. Vacca, Mark A. Wainberg, Bruce D. Walker, and Yang Wang.