Viral Proteases and Their Inhibitors provides a thorough examination of viral proteases from their molecular components, to therapeutic applications. As information on three dimensional structures and biological functions of these viral proteases become known, unexpected protein folds and unique mechanisms of proteolysis are realized. This book investigates how this facilitates the design and development of potent antiviral agents used against life-threatening viruses. Users will find descriptions of each virus that detail the structure and function of viral proteases, discuss the design and development of inhibitors, and analyze the structure-activity relationships of inhibitors. This book is ideal biochemists, virologists and those working on antiviral agents. Provides comprehensive, state-of-the-art coverage of virus infections, the virus lifecycle, and mechanisms of protease inhibition Analyzes structure-activity relationships of inhibitors of each viral protease Presents an in-depth view of the structure and function of viral proteases

-- Up-to-date and in-depth analysis.

Despite being recognized and fought against over countless centuries, human viral pathogens continue to cause major public health problems worldwide-killing millions of people and costing billions of dollars in medical care and lost productivity each year. With contributions from specialists in their respective areas of viral pathogen research, Mol

the discovery of the "splicing" of the gene transcripts, the list would include the whole molecular genetics of the lambda bacteriophage, the notions of "promotor," "repressor," and "integration," the discovery of the reverse flow of genetic information, the very existence of oncogenes, the S'-terminal "cap" struc ture of eukaryotic mRNAs, ... Electronmicroscopy, ultracentrifugation and tissue culture were the landmarks on the way of the young science. During the past few years, however, a major (and not so silent) revolution took place: recombinant DNA technology with all its might entered in our laboratories, and restriction mapping of cloned genomes and sequencing gels have replaced plaque counting and sucrose gradients. The new techniques have made it possible to "dissect" the entire genome of a virus at the molecular level, and studies that would have been dreamt of just in the mid-seventies became the everyday experiments of our days. With new insight into the structure of viral genomes, and a deeper understanding of the mechanisms that regulate their expression, our view of viruses was bound to change: this volume bears witness to this impressive advance.

Autophagy is a fundamental biological process that enables cells to autodigest their own cytosol during starvation and other forms of stress. It has a growing spectrum of acknowledged roles in immunity, aging, development, neurodegeneration, and cancer biology. An immunological role of autophagy was first recognized with the discovery of autophagy’s ability to sanitize the cellular interior by killing intracellular microbes. Since then, the repertoire of autophagy’s roles in immunity has been vastly expanded to include a diverse but interconnected portfolio of regulatory and effector functions. Autophagy is an effector of Th1/Th2 polarization; it fuels MHC II presentation of cytosolic (self and microbial) antigens; it shapes central tolerance; it affects B and T cell homeostasis; it acts both as an effector and a regulator of Toll-like receptor and other innate immunity receptor signaling; and it may help ward off chronic inflammatory disease in humans. With such a multitude of innate and adaptive immunity functions, the study of autophagy in immunity is one of the most rapidly growing fields of contemporary immunological research. This book introduces the reader to the fundamentals of autophagy, guides a novice and the well-informed reader alike through different immunological aspects of autophagy as well as the countermeasures used by highly adapted pathogens to fight autophagy, and provides the expert with the latest, up-to-date information on the specifics of the leading edge of autophagy research in infection and immunity.

The publication of this volume of The Viruses entitled The Togaviridae and Flaviviridae comes at an appropriate time. The structure and rep lication strategies of these viruses are now known to be sufficiently di verse to warrant the removal of flaviviruses from the Togaviridae family and establish them as an independent family. Flaviviridae have a special place in the history of virology. The prototype virus-yellow fever virus was the first virus to be identified as the cause of a human disease. Some of the history of this discovery is described in Chapter 1 of this volume; in Chapter 10 the complete sequence of the RNA genome of the virus is presented. This sequence not only defines the primary structure of the viral proteins, it also clarifies the mechanism of translation of the fla vivirus genome. Knowledge of the sequence of the structural proteins of these viruses represents an important step in the potential goal of using purified flavivirus glycoproteins as vaccines. Many of the chapters in this volume focus on the structure and replication of the Togaviridae. These viruses have provided valuable models for studies in cell biology, partic ularly with regard to the cotranslational and posttranslational steps re quired for the synthesis and localization of membrane glycoproteins. Fur thermore, Togaviridae have been pivotal in our growing understanding of how enveloped viruses enter and exit from cells. The broad outlines of the structure and gene expression of Togavir idae and Flaviviridae are known, but important questions remain.