Rapid progress in molecular biology, genetic engineering, and basic research in immunology has opened up new possibilities for application to diagnostic procedures and to clinical research. In a short period a new era of diagnosis dawned, covering nearly all fields of microbiology, immunology, and food technology. In consequence of this rapid development, scientists of many disciplines are involved studying infections of humans, animals, and plants or working in technical microbiology. The application of the newest findings of basic research to diagnostic work and to clinical research covers nearly all fields of microbiology and immunology. Moreover, it underlines the close relationship between diagnosis, therapy, and epidemiology. An outstanding example of these connections is given by the recent development of hepatitis B vaccine. The discovery and identification of a non cultivable agent by physicochemical and immunological methods were the heralds of a new era in the prevention of infectious diseases. This book provides an up-to-date, comprehensive review of developments and future aspects in various fields. I am convinced that the authors have succeeded in furnishing a large variety of new ideas and possibilities. K.-O. HABERMEHL Contents Time Realities in the Evaluation of Vaccines for Safety and Efficacy The Evaluation of Vaccines M. R. HILLEMAN . . . . ."

Once again the Current Topics in Microbiology and Immunology series presents a volume with up-to-date review articles on oncogenes. The well-known authority and editor of previous volumes in the series, Dr. Vogt, has accepted five contributions which critically evaluate recent research in the field.

The 12th Workshop on ""Mechanisms in B-Cell Neoplasia"" continues this series of meetings on intriguing new developments in human and experimental B-cell tumors. The integration of knowledge from basic B-cell biology to the clinical problems of multiple myelomas, follicular lymphoma, mantle cell lymphoma and B-CLL present the challenges that were discussed in the meeting.
The discussion focusses on:
- Cellular components of the "myeloma clone"
- Genomic instability in B-cells and B-cell tumors
- The CD5 antigen and B1 cells
- Regulation of cell cycle and apoptosis
- Role of IL-6, BCL-2, BCL-1, myc in B-cell development

In June 1986 a symposium was held in Giessen on Modern Trends in Virology. It was initiated by the Deutsche Forschungsgemeinschaft, which had supported virus research for the past 18 years in the Sonderforschungsbereich 47 at the University of Giessen. The purpose of the meeting was to serve as a forum for the members of the Sonderforschungsbereich to discuss scientific topics of mutual interest with about 200 virologists that had come from various parts of Europe, the United States, and Japan. It was not by chance that the symposium took place shortly after the 60th birthday of Rudolf Rott, who had founded the Sonderforschungsbereich in 1968 and has been its speaker ever since. Without his vision and his never resting energy Giessen would not have gained the position in the field of virology that it has today. This Festschrift, which contains the contributions presented at the plenary sessions of the symposium, is therefore dedicated to Rudolf Rott. HEINZ BAuER HANS-DIETER KLENK CHRISTOPH SCHOLTISSEK Table of Contents A Genetic Approach to Determining Glycoprotein Topology: The Influenza B Virus NB Glycoprotein has an Extracellular NHz-Terminal Domain Containing two N-linked Carbohydrate Chains R. A. LAMB and M. A. WILLIAMS . . . . . . . . . . . . . . . . . . . . . . . . . 1 Paramyxovirus Metabolisms Associated with the Cytoskeletal Framework Y. NAGAI, T. ToYODA, and M. HAMAGUCHI . . . . . . . . . . . . . . . . . . . 15 Correlation of High Evolutionary Rate of Influenza A Viruses in Man with High Mutation Rate Measured in Tissue Culture: A Hypothesis P. PALESE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

This volume, Biology of Poxviruses, marks our debut as editors of this well known series. We plan to continue the tradition of providing a forum for exten sive, critical reviews of individual virus groups, as exemplified by the present volume. But the pace of discovery is accelerating so rapidly that we feel the need to offer an additional format: volumes that contain collections of shorter, topical reviews on a group of related subjects. Such collections might cut across con ventional boundaries between virus groups, dealing, as an example, with a partic ular aspect of virus-cell interaction. Admittedly, this new format stretches the term "monograph" beyond the accepted definition, but we believe that we should pay that price to maintain the usefulness of the series as a medium of scientific communication. Whenever possible, we will enlist the aid of deputy editors to bring such col lections to fruition. As in the past, the editors and the publisher will welcome suggestions for topics and contributions."

The 8th volume in the Proteases in Biology and Disease series focuses on the role of proteases in virus function and their potential as anti-viral targets. Viral infections are still difficult to threat and some remained life-threatening diseases in spite of antiviral drug research over decades. Proteases are still regarded as an Achilles heel of the pathogens and, thus, protease inhibitors may help to handle the known and the emerging viral threads. The book discusses viral proteases of the most important pathogenic viruses, responsible for severe diseases: AIDS, SARS, Hepatitis, Cytomegalovirus, T-cell lymphotropic virus, Picornavirus. This book focuses specifically on the viral proteases, crucial prerequisites for viral entry into cells and viral replication. Viral proteases represent an important pharmaceutical target. The current stage of protease inhibitor development and therapy are summarised and discussed by experts in the field. This volume represents a timely and valuable continuation of the Proteases in Biology and Disease series. The reader will learn the potential for proteases as targets for effective anti-virals. This book will be a valuable source of information on viral proteases and provoke further research in this important field."

Recent years have seen unprecedented outbreaks of avian influenza A viruses. In particular, highly pathogenic H5N1 viruses have not only resulted in widespread outbreaks in domestic poultry, but have been transmitted to humans, resulting in numerous fatalities. The rapid expansion in their geographic distribution and the possibility that these viruses could acquire the ability to spread from person to person raises the risk that such a virus could cause a global pandemic with high morbidity and mortality. An effective influenza vaccine represents the best approach to prevent and control such an emerging pandemic. However, current influenza vaccines are directed at existing seasonal influenza viruses, which have little or no antigenic relationship to the highly pathogenic H5N1 strains. Concerns about pandemic preparedness have greatly stimulated research activities to develop eff- tive vaccines for pandemic influenza viruses, and to overcome the limitations inh- ent in current approaches to vaccine production and distribution. These limitations include the use of embryonated chicken eggs as the substrate for vaccine prod- tion, which is time-consuming and could involve potential biohazards in growth of new virus strains. Other limitations include the requirement that the current inac- vated influenza vaccines be administered using needles and syringes, requiring trained personnel, which could be a bottleneck when attempting to vaccinate large populations in mass campaigns. In addition, the current inactivated vaccines that are delivered by injection elicit limited protective immunity in the upper respiratory tract where the infection process is initiated.

In this book the current knowledge on human cytomegalovirus (HCMV) as a human pathogen is lucidly summarized, bringing the reader fully up to date with current knowledge concerning HCMV and all the known clincial and medical aspects of diseases caused by, and associated with, HCMV. The book is divided into four parts: (I) Human cytomegalovirus and human diseases; (II) human cytomegalovirus infections and the immunocompromised host; (III) diagnosis, treatment, and prevention of human cytomegalovirus and human diseases; and (IV) molecular aspects of human cytomegalovirus. Each part is put together from chapters written by experts in the respective fields, providing basic medical and molecular knowledge in addition to more specific understanding of HCMV infections.

ADP-ribosylating toxins have been the focus of intensive research for more than 30 years. Researchers from diverse fields of science have taken an interest in these bacterial toxins; they are studied, for example, by microbiologists, biochemists, cell biologists, and pharmacologists. There are two principal reasons for the broad and still growing interest in ADP ribosylating toxins. First, insights into the structure and functions of the toxins might be the key to prevention and treatment of diseases caused by the toxin-producing infectious micro organisms. Second, the ADP-ribosylating toxins provide potent and often unique pharmacological tools for the study of the physiological functions of their target proteins. The latter is especially the case with cholera and pertussis toxins, which both modify the IX-subunits of heterotrimeric G-proteins involved in signal transduction pathways. These toxins have proved invaluable in extending our basic understanding of the regulation of hormone-controlled signal transduction. This volume provides a review and an update of recent studies on the basic properties of bacterial ADP-ribosylating tbxins and/or exoenzymes. Our current knowledge of the cel lular entry mechanisms of ADP-ribosylating toxins is reviewed by MADSHUS and STENMARK. WILSON and COLLIER then deal with recent insights into the enzyme mechanism and active site structure of diphtheria toxin and Pseudomonas aeruginosa exotoxin A, which modify elongation factor 2. Toxins which ADP-ribosylate heterotrimeric G-proteins involved in trans membrane signal transduction are the subject of the next two chapters."

Parasitic Disease in Clinical Practice is the sixth monograph to appear in the now established and flourishing Bloomsbury Series in Clinical Science. Written by a distinguished authority in the field, the book gives a comprehensive and detailed description of parasitic infections and their clinical consequences. Such infections are no longer confined to tropical parts of the world and now have a widespread distribution. Rapid advances are being made in understanding their epidemiology and in diagnosing and treating particular infections. Current literature is largely directed to the parasites, their characteristics and their isolation; a clinical review is clearly needed. This has now been provided, for the author's stated objective is to "inculcate a greater awareness, understanding and appreciation of human parastic disease in the minds of all clinicians". London, March 1990 Jack Tinker Preface Homo sapiens has always existed in a finely balanced equilibrium with a great diversity of infective agents, almost all of them of great antiquity. Many must have exerted a profound effect on the evolution of the human genome. While the average physician is usually aware of potentially pathogenic viruses, bacteria (and rickettsia), and to a lesser extent fungi, hislher knowledge of protozoan and helminthic infections is frequently imperfect and often rudimentary.

Since the discovery of Australia antigen and its association with type B hepatitis, molecular characterization of the components making up hepatitis B virus (RBV) have been pursued with worldwide interest. Over the past two decades, such characterization has led to the development of sensitive assays to screen and exclude contaminated units from blood banks and has recently resulted in the licensing of several RBV vaccines. That more than 200 million people worldwide are chronically infected with RBV, and that they are at a high risk for the development of chronic hepatitis and hepatocellular carcinoma, still represent formidable problems in our understanding of host-virus relationships on the molecular level. In the absence of a suitable tissue culture system, and with a very limited host range of infection, characterization of RBV on the molecular level has made remarkable progress recently with the advent of genome cloning, sequencing and expression of individual virus genes by recombinant DNA technology. The presence of hepatitis B-like viruses in an expanding number of animal hosts, and the possibility of virus replication in cells other than hepatocytes, provide great promise that future work will elucidate the molecular mechanisms operative in the various outcomes of RBV infection.

Although long known as a parasite of medical and veterinary importance, interest in Toxoplasma gondii has increased with its emergence as a major cause of death in immunosuppressed individuals, and with recognition of its suitability as a model system for molecular and cellular investigations of apicomplexan parasites. The NATO workshop brought together 32 scientists working in different areas of toxoplasmosis research to gain an overview of progress in the field. Molecular studies have been carried out on genomic and extrachromosomal DNA. They reveal that Toxoplasma is very highly conserved, genetic mapping is underway and preliminary linkage analysis suggests recombination is rare; moreover all virulent strains share the same isoenzyme markers and are seen to be essentially clonal by RFLP analysis [Boothroyd, Darde, Wilson]. Despite considerable structural homology between Toxoplasma and related apicomplexan parasites there is little direct overlap in gene sequence data. Good progress has been made in cloning functional genes and in elucidation of PI anchors [Cesbron-Delauw, Johnson, Mercereau-Puijalon, Striepen]. The structure of molecules on the surface and within dense granules, rhoptries and micronemes has in some cases been determined and provides clues as to the targetting and function of these proteins.

From the preface: "The importance of the lymphatic system has been known for a long time. It was therefore surprising to learn that the status of dermal lymphatics, under both normal and pathological conditions of man, had been largely neglected to date, particularly with respect to their ultrastructure. Moreover, the existing information is incomplete, relating only to narrow segments of the skin, and it is controversial. This monograph represents an effort to overcome some of the existing deficiencies in the area of the structure (with emphasis on ultrastructure) of lymphatic capillaries. It is an account of our experience in the evaluation of dermal lymphatics in normal, edematous, and some other pathological conditions in man and in experimental animals. It is hoped that this information will prove useful for other investigators as a basis for evaluation of the structural and functional status of dermal lymphatics under a wide variety of pathological conditions."

This book is a collection of data on the tenacity in the environment of bacteria and some rickettsiae important in medicine and veterinary medicine. These data are of fundamental importance to physicians, veterinarians, epidemiologists and others when, in their practices, they are confronted with epidemics of contagious diseases or outbreaks of foodborne illnesses. At such times prompt answers are often needed to limit the problem, and thus to protect the public's health. Since data needed for such a purpose are widely distributed in the internatio nal scientific literature, the occasional desperate literature search is likely to miss some of the information that is available. This book seeks to fill that void. It lies in the nature of a compilation such as this is that it can never be totally complete. The compilation requires continual up-dating to include new information, and some currently acceptable information may have to be corrected as new data become available. However, most of the information in this compilation will never be out-of-date. The authors are always thankful for suggestions from others. Collection of the data in this book resulted from, first, several decades of studying the literature, and, second, literature searches made by the Institut fUr Dokumentationswesen in Frankfurt a. M., the Biomedi zinische Datenbank of Hoechst A. G."

Retroviruses arguably belong to the most fascinating of all viruses because of their unusual and highly efficient mode of replication involving reverse transcription and integration of the viral genome and a complex system of transcriptional and post transcriptional regulatory mechanisms. The importance of ret roviruses as human and animal pathogens has also enhanced scientific and medical interest in this diverse group of viruses and has spurred an intensive search for novel and improved antiviral agents. More recently, analysis of retroviral replication and in particular understanding the formation and composition of the virus particle has received additional attention because of the promise of retroviral vectors as vehicles for human somatic gene therapy. Many recent advances have been made in our understanding of the molecular mechanisms governing as sembly and release of infectious retrovirus particles. This book attempts to summarize these recent developments and to provide an overview of our current knowledge on retrovirus particle formation. The individual chapters of the book deal with specific steps in the pathway of retroviral morphogenesis and maturation, starting at the time when the components of the virus have been synthesized within the infected cell and ending once the infectious virion has been released from the cell. An introductory chapter provides a comparative description of the structure and morphology of various retroviruses."

In 1976 the International Committee on Taxonomy of Vi ruses (ICTV) created the family Iridoviridae to encompass several different vertebrate and invertebrate viruses that did not fit into any of the other established groups. The unifying features of this new family were (1) polyhedral symmetry; (2) large (approximately 170 kilobase pairs), lin ear, double-stranded DNA genomes; and (37) a cytoplas mic site of replication. The name "iridovirus" was derived from the observa tion that larvae infected with many of the insect viruses, as well as purified pellets of these viruses, glowed with a blue or green iridescence - presumably due to the Bragg effect of the viral crystals. However, none of the vertebrate "iridoviruses" displayed this particular characteristic. An attempt was made to substitute the more descriptive name of "icosahedral cytoplasmic deoxyribovirus," but not only was this term too unwieldy, it also did not conform to the latinized nomenclature the ICTV wished to adopt. So, for both historical and esthetic reasons, "Iridoviridae" was adopted as a family name, with Iridovirus as the genus represented by the type 1 iridescent insect virus, Tipula iri descent virus. At the 1982 ICTV Meeting, enough biochem ical data had accumulated to permit the establishment of the following five genera in the family Iridoviridae: English vernacular International Type species name name 1. Small iridescent Iridovirus Tipula iridescent virus insect virus (Type 1) 2. Large iridescent Chloriridovirus Mosquito iridescent insect virus virus (Type 2) 3."

For medical scientists, biologists and geographers interest- ed in geomedical problems the helminthiases can be a fas- cinating object of research. Their distribution is due to the in part very complicated parasite life cycles which fre- quently depend on the presence of intermediate hosts. The search for the causes of the distribution of helminthiases requires to take into account not only such geofactors as affect the parasite developmental stages outside man but go beyond this and include the entire web of factors which contribute to the conditions for the distribution of their in- termediate hosts. Last, but by no means least, it is, however, man who through his customs and habits, his settlements and dwellings, his population density and, above all, his interference in the environment, determines the distri- bution of helminthiases. The frequency, persistence and areal expansions are a consequence of the interplay and in- teraction of all the geofactors. The aim of every geomedi- cal analysis must be to prove the causes of their distri- bution through a chain of causation which has no gaps. A classic example of such a chain had already been set out in the 1920s when Ernst Rodenwaldt investigated the occur- rence of brugiasis in the Serajoe Delta on Java, and it is Rodenwaldt's analysis which has served as a model for this work. The idea of producing the monograph presented here arose from the Geomedical Monograph Series edited by Helmut 1. Jusatz.

The Brescia division of the Italian Association of Blood donors (AVIS Brescia) celebrated its 50th anniversary in 1985. The idea of organizing a Postgraduate Course on Viral Hepatitis on this occasion developed for ob vious reasons. Viral hepatitis is a major concern in blood transfusion and Brescia is located in the region of Lombardy characterized by a high HBsAg carrier rate in its population. Thus it seemed timely to convene a scientific forum in which the present state of knowledge on viral hepatitis would be summarized. This would allow us to review the tremendous progress achieved over the last 15 years, and also to focus on latest developments which pave the way for future investigation. The publication of the proceedings of this meeting was considered use ful, since it provides a tangible reminder of a comprehensive overview of the broad topic of viral hepatitis, its complications, and its connections with the practice of blood transfusion. The organizers were fortunate in obtaining the active participation of recognized experts in a variety of hepatological diSCiplines. Their contri butions summarized the more mature areas of knowledge in the field, in cluding clinical aspects, epidemiology and morphology, as well as newer developments in the forefront of hepatitis research, like new diagnostic techniques, oncogenesis, treatment, and vaccination."

On the occasion of a research visit to Thailand in my capacity as a member of the governing board of the South Asia Institute of the University of Heidelberg, I saw for the first time the severe clinical picture of dengue with haemorrhagic symptoms among Thai children. This visit had been made possible by Profes sor Dr. med. Dr. rer. nat. Ouay Ketusinh of Bangkok, to whom I wish to express my sincere thanks in this place. In 1972 the German medical literature - the periodical Medizinische Klinik, vol. 87, pp. 152-56, to be precise - had drawn attention to this new phenomenon in the disease panorama of South East Asia, indicating a change in dengue fever from being a relatively benign tropical dis ease to a form having serious clinical and epidemiological ramifications. During the ten years following my first publication the new clinical picture, described as "dengue haemorrhagic fever," has become a standard component in the Thailand's system of notifiable diseases. So too, the World Health Orga nization publishes regular reports in its Weekly Records. On March 30/31, 1981, its Regional Office for South East Asia convened a special conference in New Delhi, thus emphasizing the significance of the diffusion of this new clini cal picture in the states of South East Asia."

This book brings together various contributions aimed at the elucida tion of the structural and functional organization of the bacterial nucleoid. Most of these papers, spanning the fields of physical chemistry through biochemistry to genetics, were presented at the session on bac terial chromatin during the Symposium "Selected topics on chromatin structure and function" held at the University of Camerino, Italy, at the end of May 1985. Times when the bacterial DNA was regarded as "naked" or, at most, complexed with polyamines, and when the absence of histones and organized chromatin was considered to be a distinct feature of the pro karyotic cell, now appear remote. Our concepts of how DNA is packaged in bacteria are changing rapidly. Studies on the structure of the bacterial nucleoid are not new. Recently, however, investigations in this field have flourished again, leading to some important contributions such as the elucidation of the three-dimensional structure of what appears to be the major protein constituent of the bacterial nucleoid or the development of methods to titrate the extent of DNA supercoiling within the bacterial cell."

Rapid progress continues to be made in understanding the molecular and cellular events that comprise B-Iymphocyte differentiation. This is due in part to the high level of inter est shown by many investigators from diverse disciplines, who find this subject suitable for addressing some of the fundamental issues of immunobiology. B-cell developmen tal models are being extensively used to investigate cell-cell interactions, molecular mediators of differentiation and proliferation, differential onset of gene programs, and gene rearrangement and expression, as well as the generation of the immune response itself. Not surprisingly, increased understanding of B-cell differentiation sometimes results from the application of new techniques that permit greater insight into the cells comprising the system and the genetic mechanisms by which these cells express their differentiative potential. However, experimental strategies based upon the novel application of established technologies have also led to the clarification of many issues, as well as to the discov ery of previously unrecognized problems. One problem, well recognized by those active in the field, is how to keep up with significant developments as they appear. The purpose of this book, part of a series devoted to analysing current issues in biology, is to help overcome this problem. No attempt at comprehensive cov erage of all of the issues has been made. Rather, a more thorough analysis of a few topics is presented."

The third component of complement, C3, is one of the most versatile proteins and an important participant in immune surveillance and immune response pathways. Its multifunctio nality is based on its ability to interact specifically with multiple serum complement proteins, cell surface receptors, and mem brant;-associated regulatory proteins. One of its most intriguing strategies of interaction with cell surfaces is the covalent binding of activated C3 through the internal thioester. The field has expanded over the past 10 years and a wealth of information has accumulated. C3 from various species and many of the human C3 binding proteins have been cloned and expressed. Numerous cellular responses mediated by the diffe rent fragments of C3 have been described. The findings that C3 interacts in a ligand-receptor-like fashion with proteins of nonself origin such as the gC of herpes simplex virus, a 70-kDa protein from Candida albicans, proteins from Epstein-Barr virus, etc. has opened a new field of investigation. The papers assembled in this volume summarize the wealth of data on the various aspects of the C3 interactions; together they bring to the reader new information on the chemistry, molecular gene tics, biology, and pathophysiology of C3 and C3-binding proteins. Emphasis is given to structural features as they relate to functions. Spring 1989 JOHN D. LAMBRIS, HANS J. MULLER-EBERHARD Table of Contents J. E. VOLANAKIS: Participation of C3 and Its Ligands in Complement Activation . . . . . . . . . . . 1 S. R. BARNUM, G. FEY, and B. F. TACK: Biosynthesis and Genetics of C3 . . . . . . . . . . . . .

Interest in the lentivirus subfamily of retroviruses has greatly intensified due to the realization that HIV-1 and HIV-2 are members of this previously obscure group. Related lentiviruses have now been isolated from sheep, goats, horses, cattle, cats, monkeys, and humans. This issue of CTMI is devoted to the lentiviruses of nonhuman primates, referred to as simian immunodeficiency viruses (SIVs). The SIVs provide valuable tools for our quest to understand and control the HIVs, which are obviously important new human pathogens. Included in this volume are discussions of the distribution and molecular phylogeny of the SIVs and their use as animal models for the study of AIDS pathogenesis, and the chapters clearly illustrate how SIV models are contributing to our understanding of the ability of host immune responses to control infection at least temporarily and the ability of virus to evade these host immune defenses.