The three years since our last conference in San Francisco have again seen a dramatic expansion of the number of antivirals either licensed or in the late stages of clinical trials. d4T is now licensed for HIV infection, famciclovir and the oral pro-drug of acyclovir, valacyclovir, are now licensed for VZV infections in some countries. Moreover. oral ganciclovir, cidofovir, and sorivudine are not far behind. Clinical trials with the second-site reverse transcriptase inhibitors and the protease inhibitors for HlV infection are proceeding rapidly and on a broad scale, and the preliminary results would suggest that several of these classes of drugs will be licensed as well. Despite this optimism, however, there is increasing evidence that antiviral-resistant strains of pathogenic viruses will be a significant problem, perhaps especially with therapy of HIV infection, and there remains a desperate need for improved drugs (with either improved efficacy or decreased toxicity, or both) for CMV and HIV infections. This book is the edited proceedings of the Fourth Triennial Conference on Antiviral Chemotherapy, held in San Francisco, in November 1994. The conference was sponsored by the University of California, San Francisco, and co-sponsored by the International Society for Antiviral Research (ISAR), the Macfarlane Burnet Centre for Medical Research in Melbourne, Australia, and the Australian National Centre for HIV Virology Research. The conference had been organized to present an overview of the field of antiviral chemotherapy.

This comprehensive account of the human herpesviruses provides an encyclopedic overview of their basic virology and clinical manifestations. This group of viruses includes human simplex type 1 and 2, Epstein–Barr virus, Kaposi's Sarcoma-associated herpesvirus, cytomegalovirus, HHV6A, 6B and 7, and varicella-zoster virus. The viral diseases and cancers they cause are significant and often recurrent. Their prevalence in the developed world accounts for a major burden of disease, and as a result there is a great deal of research into the pathophysiology of infection and immunobiology. Another important area covered within this volume concerns antiviral therapy and the development of vaccines. All these aspects are covered in depth, both scientifically and in terms of clinical guidelines for patient care. The text is illustrated generously throughout and is fully referenced to the latest research and developments.

" . . . the motto for the therapeutics of the future will have to be de sedibus et causis pharmacorum. " P. EHRLICH, 1909 Exciting events in the basic disciplines of virology, immunology, and pharmacology continue to advance the understanding of the pathogenesis and control of virus diseases. At the same time, the rational development of antiviral agents is attracting, to an increasing extent, the interest of workers in other disciplines. Improvements in technology facilitate the definition of potential target sites for antiviral intervention and unmask new viral and host genes. The outcome is a further steady development of new antiviral agents which approach the "magic bullets" first proposed by PAUL EHRLICH. Remarkable advances in protein synthetic methods that yield polypeptides which inhibit active sites of viral proteins have aided substantially in the basic and clinical study of these antiviral agents. In addition, the extremely rapid progression in recombinant DNA techniques, leading to the synthesis of large quantities of gene products, is also increasing our opportunities at a dashing pace. New information and developing technology facilitate research on the mechanism of action, toxicity, pharmacokinetics, and pharmacodynamics of new agents. The list of clinically effective antiviral agents is expanding and the number of potentially useful compounds is growing rapidly. This book is a combined theoretical text and practical manual which, it is hoped, will be of use to all who have an interest in virus diseases, particularly scientists, physicians and graduate students.

Considerable advances have been made in the treatment of antiviral diseases over the last decade. Several new drugs have been introduced while new clinical information has been gathered on the efficacy of existing drugs. This study aims to provide an examination of the basic science (drug formulae, structure and biochemical activity) and clinical information (usage and efficacy) on chemotherapy, as well as describing future potentials.

Viral Pathogenesis: From Basics to Systems Biology, Third Edition, has been thoroughly updated to cover topical advances in the evolving field of viral pathogenesis, while also providing the requisite classic foundational information for which it is recognized. The book provides key coverage of the newfound ability to profile molecular events on a system-wide scale, which has led to a deeper understanding of virus-host interactions, host signaling and molecular-interaction networks, and the role of host genetics in determining disease outcome. In addition, the content has been augmented with short chapters on seminal breakthroughs and profiles of their progenitors, as well as short commentaries on important or controversial issues in the field. Thus, the reader will be given a view of virology research with perspectives on issues such as biomedical ethics, public health policy, and human health. In summary, the third edition will give the student a sense of the exciting new perspectives on viral pathogenesis that have been provided by recent developments in genomics, computation, modeling, and systems biology. - Covers all aspects of viral infection, including viral entry, replication, and release, as well as innate and adaptive immunity and viral pathogenesis - Provides a fresh perspective on the approaches used to understand how viruses cause disease - Features molecular profiling techniques, whole genome sequencing, and innovative computational methods - Highlights the use of contemporary approaches and the insights they provide to the field

Scientists and clinicians attending the last "New Directions in Antiviral Therapy" conference in late 1994 could hardly have predicted the revolution in the management of patients with HIV infection that has occurred since. Two new classes of antiretrovirals have been licensed, the second-site RT inhibitors and the protease inhibitors; the long in cubation period of active HIV infection, when the infection is clinically latent, is now un derstood to be a period of intense viral replication and turnover of CD4 lymphocytes; measurements of HI V RNA concentration in plasma have been shown to be essential tools for monitoring the course of HIV infection, deciding when to treat, and assessing the re sults of treatment; and finally, combinations of antiretrovirals, particularly combinations including protease inhibitors, have been shown to have dramatically beneficial effects on patients with HIV infection. These advances, coupled with new drugs for the management of herpesvirus infections, have made dramatic differences in the quality and length of life of HIV-infected patients. Additional advances have been made since 1994 in the prevention or management of influenza virus (zanamavir), respiratory syncytial virus (palvizumab), hepatitis B virus (lamivudine and famciclovir), and enterovirus infections (pleconaril). It is difficult to re member that only slightly more than a decade ago there were only a handful of antiviral agents available (none of which were antiretrovirals), and a number of those were either highly toxic, of dubious efficacy, or both.

Antiviral chemotherapy has come of age, and, after an initial slow pro gress, the development of new antiviral agents has proceeded at a more rapid pace and the perspectives for their clinical use have increased considerably. Now, 25 years after the first antiviral assay (idoxuridine) was introduced in the clinic, it is fitting to commemorate the beginning of the antivirals' era. In its introductory chapter B.E. Juel-Jensen touches on what may be con sidered as five of the most fundamental requirements of an antiviral drug : efficacy, relative non-toxicity, easy solubility, ready availability and rea sonable cost. Surely, the antiviral drugs that have so far been used in the clinic could still be improved upon as one or more of these five essential demands are concerned. How is all began is narrated by W.H. Prusoff. The first antiviral drugs to be used in humans were methisazone and idoxuridine, the former, which is now of archival interest, in the prevention of smallpox, the latter, which was approved for clinical use in the United States in 1962, for the topical treatment of herpetic keratitis. In terms of potency, also because of solubility reasons, idoxuridine has been superseded by trifluridine in the topical treatment of herpes simplex epithelial keratitis. H.E. Kaufman did not find trifluridine or acyclovir ef fective in the treatment of deep stromal keratitis or iritis and he reckons that other antiviral drugs (i.e. bromovinyldeoxyuridine) would not be effec tive either.