Richard J. Whitley

Bernard Roizman

Carlos Lopez

Ryoichi Mori

No one whose opinion deserves a moment's consideration can doubt that most of the great positive evils of the world are in themselves removable, and will, if human affairs continue to improve, be in the end reduced to narrow limits. J. S. Mill, Utilitarianism, II, 1863 Mill was not writing about herpesviruses, but had he known them as we do, he would have included them among the great positive evils of the world. They cause disease and premature death, and are very costly to our society. There is no loftier aim than to cure or prevent human infections with these viruses. The objective of much of the current research on herpesviruses is directed toward an understanding of the molecular mechanisms involved in initiation of infection, establish ment and termination of latent state, virus multiplication, and the destruction of cells which ultimately is the basis of the diseases caused by these viruses. At no time during the past 80 years, since members of the herpesvirus family were first discovered, has there been so much progress in our understanding of the biology of these viruses as in the past few years. Along with the development of a greater understanding of the molecular biol ogy of the well-known herpesviruses we have witnessed the isolation of new human herpes viruses.

Immunobiology and Prophylaxis of Human Herpesvirus Infections

A great truth is a truth whose opposite. is also a great truth. Thomas Mann (Essay on Freud, 1937) This volume centers on pseudorabies (PR V), herpes simplex viruses 1 and 2 (HSV-1 and HSV-2), and human cytomegalovirus (CMV) and fulfills three objectives. The chapters on the epidemiology and latency of HSV, and on the glycoproteins specified by HSV and CMV, set the stage for the discussions of the immunobiology and pathogenesis of human herpesvirus infections in Volume 4. The epidemiology of HSV is the basis of our understanding of the spread and survival of this virus in the human populations. Central to the epidemiology of HSV and its pathogenesis in humans is the ability of the virus to remain in a latent state for the life of its host. The viral membrane glycoproteins are among the most interesting virion proteins, primarily because of their critical role in the initiation of infection. Since they are the surface membrane proteins of the virion and appear on the surface of productively infected cells, they are also the obvious if not the exclusive targets of the immune response. The chapters on the transforming potential of HSV and CMV, and on the role of HSV in human cancer, deal with challenging problems requiring rather different experimental tools.

Volume 3

The Herpesviruses

The first volume of the nineteen-volume series entitled Comprehensive Virology was published in 1974 and the last is yet to appear. We noted in 1974 that virology as a discipline had passed through its descriptive and phenomenological phases and was joining the molecular biology rev olution. The volumes published to date were meant to serve as an in depth analysis and standard reference of the evolving field of virology. We felt that viruses as biological entities had to be considered in the context of the broader fields of molecular and cellular biology. In fact, we felt then, and feel even more strongly now, that viruses, being simpler biological models, could serve as valuable probes for investigating the biology of the far more complex host cell. During the decade-long compilation of a series of books like Com prehensive Virology, some of the coverage will obviously not remain up to-date. The usual remedy to this aspect of science publishing is to pro duce a second edition. However, in view of the enormous increase in knowledge about viruses, we felt that a new approach was needed in covering virology in the 1980s and 1990s. Thus we decided to abandon the somewhat arbitrary subgrouping of the subject matter under the titles Reproduction, Structure and Assembly, Regulation and Genetics, Addi tional Topics, and Virus-Host Interactions. Instead we have organized a new series entitled The Viruses.

Pathogenesis, Diagnosis, and Treatment

Human Herpesvirus Infections

'You damn sadist/said mr cummings 'you try to make people think. ' -Ezra Pound (Canto 89) What makes herpesviruses unique? It is certainly not the size of their genomes or the individual features of their reproductive cycle, although in toto striking features that are exclusive to the herpesviruses abound. Unquestionably, the pre-eminent feature is the relationship of herpes viruses with their natural hosts. As described in preceding volumes, all herpesviruses seem to be able to colonize and to remain in a latent, nonproductive form for life of their hosts. Once established in the host, the relationship is best described as that of an armed truce. What happens when this truce breaks down or when the host encounters the virus for the first time is the subject of this volume. We have focused primarily on the five human herpesviruses [herpes simplex virus 1 (HSV-l), herpes simplex virus 2 (HSV-2), cytomegalovirus (CMV), varicella zoster virus (VZV) and Epstein-Barr virus (EBV)] because much more is known about them than about any other herpesviruses, and because it is of interest to compare both the diversity of manifestations of infections with human herpesviruses and the spectrum of human responses to these viruses. This volume summarizes the current knowledge of the pathogenesis and immunobiology of herpesvirus infections in man and describes new and developing approaches to prophylaxis and treatment. It contains con tributions from distinguished research scientists presently engaged at the forefront of these scientific investigations.

Richard Whitley

Koichi Yamanishi

Edward Mocarski

Ann Arvin

Patrick S. Moore

Gabriella Campadelli-Fiume

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.

Bernard Roizman

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