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.
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 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 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.
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.
In eukaryotic cells, the nuclear genome and its transcriptional apparatus is separated from the site of protein synthesis by the nuclear envelope. Thus, a constant flow of proteins and nucleic acids has to cross the nuclear envelope in both directions. This transport in and out of the nucleus is mediated by nuclear pore complexes (NPCs) and occurs in an energy and signal-dependent manner. Thus, nucleocytoplasmic translocation of macro molecules across the nuclear envelope appears to be a highly specific and regulated process. Viruses that replicate their genome in the cell nucleus are therefore forced to develop efficient ways to deal with the intracellulZlr host cell transport machinery. Historically, investigation of Polyomavirus replication allowed identification ofsequences that mediate nuclear import, which led subsequently to our detailed understanding of the cellular factors that are involved in nuclear import. Transport ofmacromolecules in the opposite direction, however, is less well understood. The investigation of retroviral gene expression in recent years pro vided the first insights into the cellular mechanisms that regulate nuclear export. In particular, the detailed dissection of the function of the human immunodeficiency virus type I (HIV-I) Rev trans-activator protein identified CRMI, as a hona fide nuclear export receptor. CRM I appears to be involved in the nucleocytoplasmic translocation of the vast majority of viral and cellular proteins that have subsequently been found to contain a Rev-type leucine-rich nuclear export signal (NES).
The world continues to lose more than a million lives each year to the HIV epidemic, and nearly two million individuals were infected with HIV in 2017 alone. The new Sustainable Development Goals, adopted by countries of the United Nations in September 2015, include a commitment to end the AIDS epidemic by 2030. Considerable emphasis on prevention of new infections and treatment of those living with HIV will be needed to make this goal achievable. With nearly 37 million people now living with HIV, it is a communicable disease that behaves like a noncommunicable disease. Nutritional management is integral to comprehensive HIV care and treatment. Improved nutritional status and weight gain can increase recovery and strength of individuals living with HIV/AIDS, improve dietary diversity and caloric intake, and improve quality of life. This book highlights evidence-based research linking nutrition and HIV and identifies research gaps to inform the development of guidelines and policies for the United Nations’ Sustainable Development Goals. A comprehensive approach that includes nutritional interventions is likely to maximize the benefit of antiretroviral therapy in preventing HIV disease progression and other adverse outcomes in HIV-infected men and women. Modification of nutritional status has been shown to enhance the quality of life of those suffering HIV/AIDS, both physically in terms of improved body mass index and immunological markers, and psychologically, by improving symptoms of depression. While the primary focus for those infected should remain on antiretroviral treatment and increasing its availability and coverage, improvement of nutritional status plays a complementary role in the management of HIV infection.
A comprehensive compilation of research techniques necessary for investigating the virology, immunology and molecular biology of HIV-1. Protocols are also provided which represent state of the art approaches to a wide spectrum of HIV related issues.