Scientific research on dengue has a long and rich history. The literature has been touched by famous names in medicine- Benjamin Rush, Walter Reed, and Albert Sabin, to name a very few- and has been fertile ground for medical historians . The advances made in those early investigations are all the more remarkable for the limited tools available at the time. The demonstration of a viral etiology for dengue fever, the recognition of mosquitoes as the vector for transmission to humans, and the existence of multiple viral variants (serotypes) with only partial cross-protection were all accomplished prior to the ability to culture and characterize the etiologic agent. Research on dengue in this period was typically driven by circumstances. Epidemics of dengue created public health crises, although these were relatively short-lived in any one location, as the population of susceptible individuals quickly shrank. Military considerations became as a major driving force for research. With the introduction of large numbers of non-immune individuals into endemic areas, dengue could cripple military readiness, taking more soldiers out of action than hostile fire. Dengue and dengue hemorrhagic fever, which assumed pandemic proportions during the latter half of the last century, have shown no indication of slowing their growth during this first decade of the twenty-first century. Challenges remain in understanding the basic mechanisms of viral replication and disease pathogenesis, in clinical management of patients, and in control of dengue viral transmission. Nevertheless, new tools and insights have led to major recent scientific advances. As the first candidate vaccines enter large-scale efficacy trials, there is reason to hope that we may soon "turn the corner" on this disease.

The first volume of Antibiotics was published in 1967 and contained a series of review papers on antibiotic actions. The editors, Drs. GOTTLIEB and SHAW, were aware of the rapid development of this field of study and provided a number of addenda in an effort to keep knowledge up to date while the book was in production. One year after the publication of Antibiotics I, this editor had a conference with Dr. KONRAD F. SPRINGER in which it became clear that another volume on actions of antibiotics would be necessary. For a variety of reasons, this was delayed until 1975 and became Antibiotics III. It did not contain addenda since it was recognized by the editors, Drs. CORCORAN and HAHN, that still another volume would have to follow and that in a moving field, such as the study of the actions of antibacterial drugs, no publication can be definitive or remain current, except for a limited period of time. The editors of Volume III grouped the contributions into sections: 1. Inter ference with nucleic acid biosyntheses, 2. Interference with protein biosynthesis, and 3. Interference with cell wall/membrane biosynthesis, specific enzyme sys tems, and those in which the mode of action was not known with certainty."

Presented here are recent achievements in molecular biology of non-pathogenic yeast and filamenous fungi as well as of human pathogens. Thebook is diveded into 4 sections: - Molecular Biology of Yeast; - Molecular Biology of Filamenous Fungi; - New Tools and Prospectives for Medical Mycology; - Fungal Morphogenesis. It focuses on aspects of medical mycology, namely isolation of specific genes and strategies for developing new targets for antifungal therapy.

This book is a collection of critical reviews about a diverse group of virus families with two features in common: the stable repository of genetic information in each virus is RNA, and each virus modifies and appropriates a particular patch of the eukaryotic cell membrane system to complete its structure. The reviews take the reader from the level of virus genome structure and expression through the quaternary interactions between virus-specified elements and cellular components that cooperate to produce virus particles. There are spectacular illustrations in this volume, but it is much more than a picture gallery. Reading widely in this book can be an effective antidote to overspecialization: in these pages, you are likely to learn much about viruses and about cells that you didn't know before; you'll discover illuminating parallels between diverse virus families; you'll come away with a sharpened awareness of important things that are still to be learned. Memphis, Tenn. , Summer 1984 David W. Kingsbury Preface This book was written at the suggestion of Dr. David W. Kingsbury made at a work shop on viruses organized by the Multiple Sclerosis Society in Aspen, Colorado, U. S. A. , three years ago. Originally, we had thought to focus on the morphological aspects of viral assembly. Later, during our discussions on the process of budding of enveloped RNA viruses, it became evident that we should include biochemical data in our review and correlate them with the structural aspects of virus maturation.

JAMES L. MCGAUGH Understanding of the nature and functions of neurotransmitter systems in the brain has increased enormously in recent decades. Lack of knowledge required us, not too long ago, to use the adjective "putative" when discussing transmitters. Such caution is no longer essential (at least for a number of transmitters). Impressive progress has been achieved in understanding the pharmacology, biochemistry and anatomy of transmitter systems. There has, however, been relatively less progress in understanding the functioning of brain transmitters in regulating and mediating behavior. A simple and certainly correct explanation for this is, of course, that understanding of neurotransmitter functions requires prior detailed knowledge of basic pharmacology, biochemistry and anatomy. Beyond that, it now seems likely that progress in understanding the functions of brain neurotransmitters will proceed only as we examine the interactions of neurotransmitter systems in regulating behavioral functions. This premise is, of course, suggested by the findings of studies of the chemical neuroanatomy of the brain: Neurotransmitter systems are influenced by other neurotransmitter systems and, in tum, influence the same as well as other systems. No system works alone. The chapters in this book explicitly examine the interactions of neurotransmitter systems involved in the regulation of cognitive processes. The facts and interpretations offered provide compelling support for the premise that cognitive processes are orchestrated by interactions among neurotransmitter systems. And, they offer promise that understanding of such interactions will be of critical importance in the develop ment of treatments for brain diseases affecting cognitive functioning."

The use of biotechnical processes in control of environmental pollution and in haz ardous waste treatment is viewed as an advantageous alternative or adduct to phys ical chemical treatment technologies. Yet, the development and implementation of both conventional and advanced biotechnologies in predictable and efficacious field applications suffer from numerous technical, regulatory, and societal uncertainties. With the application of modern molecular biology and genetic engineering, there is clear potential for biotechnical developments that will lead to breakthroughs in controlled and optimized hazardous waste treatment for in situ and unit process use. There is, however, great concern that the development of these technologies may be needlessly hindered in their applications and that the fundamental research base may not be able to sustain continued technology development. Some of these issues have been discussed in a fragmented fashion within the research and development community. A basic research agenda has been established to promote a sustainable cross-disciplinary technology base. This agenda includes developing new and improved strains for biodegradation, improving bioanalytical methods to measure strain and biodegradation performance, and providing an in tegrated environmental and reactor systems analysis approach for process control and optimization."

Study of parasitology, like any other branch of biological science, has in recent years been increasingly revealing and rewarding with enrichment and embellishment by basic sciences, specially with application of spectacular advances in molecular biology and biotechnology. Such a fruitful fusion of more than one discipline has now come to characterise more than ever before our approach to the subject. This volume of helminthology with contributions from a galaxy of distinguished scientists in specific areas, bears an eloquent testimony to the gratifying yield that accrues from cross fertilisation of multiple disciplines and able support from basic sciences. Matazoan parasites, helminths, living in more than one host in different stages of development, present an intricate spectrum of host-parasite relationship, which has evolved through diverse frame and flow of ecologic circumstances. The situation is further complicated, as elaborated here, by genotypic and phenotypic variations, which profoundly influence the dynamic interaction between hosts and parasites and determine consequently survival and propagation of the latter. Indeed, one of the important messages upheld in this book is that genetic endowment of parasites plays a pivotal role in their immunogenicity, pathogenicity, response to variable environmental composition, including drug response and also their transmission dynamics and epidemiology. Evolution of parasitic helminths with concomitant physiologic and morphologic alterations have been traced from free-living stage to development of host-specificity of different degrees and parasitic speciation.

The time seems ripe for a critical compendium of that segment of the biological universe we call viruses. Virology, as a science, having passed only recently through its descriptive phase of naming and numbering, has probably reached that stage at which relatively few new-truly new-viruses will be discovered. Triggered by the intellectual probes and techniques of molecular biology, genetics, bio chemical cytology, and high resolution microscopy and spectroscopy, the field has experienced a genuine information explosion. Few serious attempts have been made to chronicle these events. This comprehensive series, which will comprise some 6000 pages in a total of 19 volumes, represents a commitment by a large group of active investigators to analyze, digest, and expostulate on the great mass of data relating to viruses, much of which is now amorphous and disjointed, and scattered throughout a wide literature. In this way, we hope to place the entire field in perspective, and to develop an invaluable reference and sourcebook for researchers and students at all levels. This series is designed as a continuum that can be entered any where, but which also provides a logical progression of developing facts and integrated concepts."

The eighth workshop in this series on Mechanisms in B-Cell Neoplasia 1990 was held in Wilson Hall at the National Institutes of Health, Bethesda, Maryland on March 28-30. Five major topics formed the basis for the discussions: 1) progress in experimental models of B-cell tumorigenesis, 2) the role of IL-6 in plasma cell tumor formation with particular emphasis on human myeloma, 3) immortaliza tion and regulation of mitosis in B-cells, 4) the mYQ gene in B-cell neoplasia, and 5) the role of EBV and other oncogenes in transforma tion of human B-Iymphocytes. A meeting on the Epidemiology of Myeloma was held at the N. I. H. on the preceding day, and many of those interested in the clinical aspects of myeloma were also participants at the workshop. Experimental Models of B-Cell Tumor Development We have seen in the last eight years the steady growth of model experimental systems, many of which have been designed to be counter parts of the major forms of human B cell tumors, e. g., follicular lymphomas, Burkitt's lymphomas, acute B-cell leukemia and multiple myeloma. A variety of novel ways of inducing these tumors has been described. Advantage has been taken of the "experiments in nature" to identify critical genes that playa role in tumor pathogenesis. These genes have been identified by being near to viral insertion and chromosomal translocation sites, or by having been incorporated or transduced into a defective transforming retrovirus."

Given the continuing high level of concern among health professionals and the general public about issues related to AIDS, this volume on testing for AIDS and related viruses is extremely timely. The book has been written by experts in the area of AIDS testing, many of whom are at the Centers for Disease Control. The book includes several chapters which compare the different laboratory tests available for detecting the AIDS virus (HIV). It also addresses such topics as ethical considerations in AIDS testing, HIV infection in children, testing for other human viruses related to HIV, safety practices in HIV-testing laboratories, and managing occupational exposure to HIV. The book is intended for public health officials involved in HIV testing, hospital administrators and clinical laboratory directors responsible for setting up HIV testing programs, and physicians concerned with testing for AIDS.

Almost 50 million persons visit another continent each year. It is mainly those 15-18 million travelers from industrialized nations who visit or reside in developing countries that are at increased health risk. To develop effective health protection advice, the health risks of travel and the benefits of prophylaxis (vaccines, new and old drugs, behaviour modification, etc.) should be assessed systematically. The purpose of this book is to improve the protection of the travelers' health by more effective and more uniform recommendations. It contains many data on recent research and represents the first comprehensive account on travel medicine for professionals.

The advancement of science is ever more contingent upon the interaction of experts vast amount of scientific information being gathered every day that exceeds the ability of any one scientist to acquire. As an illustration of the frantic pace of scientific disc- more acute in the case of scientific fields at the interface of different and seemingly distant areas of study. Amidst these, the field of cell encapsulation brings together an array of diverse disciplines such as molecular biology and biopolymers, gene therapy and inorganic membranes, stem cell biology and physicochemistry, immunology and nanotechnology. Clearly, such range of topics is too broad for any individual scientist the state-of-the-art in the field of cell encapsulation. At the core of this technology, there is an interaction of physicochemical and biological elements forming three distinct layers of complexity. First, the chemistry of the biopolymer dictates the degree of protein adsorption, vascularization, tox- ity and biocompatibility of the microcapsules. Advances in biopolymer science are providing solutions to overcome existing challenges and to improve microcapsules as delivery vehicles. Second, the choice of cells, and more precisely the plethora of in determining the immune response elicited by the host to implanted microcapsules.

Our gut is colonized by numerous bacteria throughout our life, and the gut epithelium is constantly exposed to foreign microbes and dietary antigens. Thus, the gut epithelium acts as a barrier against microbial invaders and is equipped with various innate defense systems. Resident commensal and foreign invading bacteria interact intimately with the gut epithelium and can impact host cellular and innate immune responses. From the perspective of many pathogenic bacteria, the gut epithelium serves as an infectious foothold and port of entry for disseminate into deeper tissues. In some instances when the intestinal defense activity and host immune system become compromised, even commensal and opportunistic pathogenic bacteria can cross the barrier and initiate local and systematic infectious diseases. Conversely, some highly pathogenic bacteria, such as those highlighted in this book, are able to colonize or invade the intestinal epithelium despite the gut barrier function is intact. Therefore, the relationship between the defensive activity of the intestinal epithelium against microbes and the pathogenesis of infective microbes becomes the basis for maintaining a healthy life. The authors offer an overview of the current topics related to major gastric and enteric pathogens, while highlighting their highly evolved host (human)-adapted infectious processes. Clearly, an in-depth study of bacterial infectious strategies, as well as the host cellular and immune responses, presented in each chapter of this book will provide further insight into the critical roles of the host innate and adaptive immune systems and their importance in determining the severity or completely preventing infectious diseases. Furthermore, under the continuous threat of emerging and re-emerging infectious diseases, the topic of gut-bacteria molecular interactions will provide various clues and ideas for the development of new therapeutic strategies.

nomenon [26]. Indeed, Krieg et al. [21] showed that the elimination of the CpG in a particular ODN invariably abolished immune stimulation, but changes in the ODN sequences that did not affect the CpG or the flanking bases did not alter the immuno- stimulatory (IS) effect. Furthermore, they extended the initial observations of the IS effects to non-palindromic CpG-enriched ODN [21]. Subsequent studies showed that CpG-enriched ODN also induce the secretion of IL-6 and IL-12 [19] and IFN-a [6, 27]. By adding or deleting various IS sequences (ISS)-ODN to or from different pDNAs, it was demonstrated that the ISS have a pivotal role in the induction of the subsequent immune response to the gene product in gene-vaccinated animals. The enhanced Thl immune response induced by gene vaccination is the consequence of the activation of the innate immune response by the ISS in the pDNA backbone [30, 31], rather than the low dose of intracellularly produced antigen. The cell activation products induced by the ISS, i. e. , IFN-a [3], IFN-~ [43], IL-12 [37], and IL-18 [25], are established inducers of IFN-y synthesis and promote the differentiation of naive T helper cells to Thl lym- phocytes. Thus, the ISS activate the precise innate cytokine network required to pro- mote Thl differentiation (see Fig. 1). In a recent study it was demonstrated that this ap- proach is also applicable to a protein antigen.

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."

Genital Papillomavirus Infections provides a state of the art survey on the clinical aspects, diagnosis, treatment, and prevention of genital papillomavirus infections, written by experts in the respective fields. Two introductory sections on epidemiology and molecular biology are followed by chapters on new techniques for the detection of genital papillomaviruses and their presence in genital carcinomas. Contributions on the clinical aspects cover infections of the cervix, male and female external genitalia, urethra, and oral cavity. A discussion of the immunobiology of papillomaviruses ends in an evaluation of the prospects for vaccination, and the application of podophyllotoxin, cryosurgery, laser therapy, and interferon treatment are described in detail. This book is unique in placing a strong emphasis on clinical aspects of genital papillomavirus infections. Mainly addressed to clinicians, it provides practical guidelines on methods for their diagnosis and treatment.

In the rapidly evolving field of Helicobacter infection new data on pathogenetic and pathophysiological mechanism have appeared. New methods which will be more sensitive and specific in the diagnosis of the infection are being developed and in this proceedings the first attempt using PCR technology is published. From the clinical point of view, a challenging aspect that needs clarification, is the observation which suggests an appearance of a correlation between the presence of the bacteria and abdominal pain and other symptoms in children whereas in old age no such correlation is evident. The relationship of H. pylori and gastric cancer is studied with histopathological data and epidemiological approaches. On the treatment side schemes using short courses and new antibiotic combinations are being investigated and preliminary data are reported.

Natural resistance is now coming to be recognized as a potentially important phenomenon in host defense against infection and ma lignancy. Genetically controlled resistance mechanisms are usUally effective early in infection and before conventional immune responses are generated. Comparisons of experimental systems where natural resistance plays a prominent role demon strate the complexities of the host defense mechanisms involved, as evidenced in the present volume. Nevertheless, some com mon components of genetic resistance are discernible and largely comprise natural killer cells, macrophages, and interferon These and additional factors would seem to constitute a first line of de fense in host resistance against both viruses and tumors. It is evi dent that considerable variation in the relative importance of di stinct mechanisms may be found among various resistance sy stems and that, most likely, additional effector functions will be discovered. Resistance to tumors and most viruses is under polygenic control, has a complex mode of inheritance, and depends on appro priately complex effector mechanisms. Instances, however, whe re a single gene locus determines resistance or susceptibility to a virus, as in the case of resistance to flaviviruses or influenza viru ses, would seem to offer good prospects for elucidating the basic factors involved. Resistance to influenza virus would indeed seem to represent a comparatively simple situation: resistance is expressed at the host cell level, and interferon is its main media tor. The present volume provides insight into current concepts of such resistance mechanisms."

It goes almost without saying that there has been a marked increase in the incidence of sexually transmitted diseases throughout the world in the past two to three decades. Indeed, despite the progress that has been made in methods of diagnosis and treatment, the sexually transmitted diseases as a whole are the most common communicable diseases and as such constitute an important health problem. The increase in incidence may be accounted for by changes in sexual behaviour, the introduction of contraceptives and the increasing mobility of the population. In addition, during the same time period, the number of infectious agents recognized as being sexually transmitted has increased considerably. These include Chlamydia trachomatis, herpes simplex virus, cytomegalovirus and hepatitis B virus. Indeed, some are as dependent on sexual transmission as the agents which cause the traditional venereal diseases and collectively they cause morbidity which has out-stripped that caused by gonorrhoea and syphilis. It could almost be said that to know the sexually transmitted diseases is to know micro biology. However, the approach taken in this book has not been to consider individual infectious agents and evaluate what they do and do not cause but to consider clinical conditions and what might be responsible for them. To cover the complete spectrum of the sexually transmitted diseases in a comprehensive way now takes a text book of massive proportion."

The substantial and impressive changes in microbial ecology can scarcely be chronicled in a meaningful fashion, and a review series such as Advances in Microbial Ecology can thus not do justice to the numerous studies that have been published in recent years. On the other hand, the mere existence of this series bears testimony to the many and diverse activities. The growing concern with microbial communities and processes in natural ecosystems is not restricted to scientists in one region and is not limited to particular groups of organisms or to individual theoretical or applied problems. The recent and successful international symposium on microbial ecology held in New Zealand-sponsored in part by the International Commission on Microbial Ecology, as is the Advances-and the general microbiology and ecology conferences and congresses have included reports from investigators from all corners of the globe and have explored both new and traditional areas, agricultural and public health problems, individual species and complex communities, and heterotrophs and autotrophs as well as ecosystem models relying on mathematical concepts and environmental processes needing sophisticated chemistry for their definition. The reviews in the present volume thus can offer only a minute sampling of the multitude of topics being actively explored at the present time. Two of the reviews focus attention on biogeochemical cycles regulated by microorganisms, in particular the way these organisms contribute to or control the levels and identities of chemical substances in the atmosphere. The chapter by Y. Dommergues, L. W. Belser, and E. L.

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 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

The larvae of Anisakis, whose adult form lives on sea mammals such as whales, seals, and dolphins, are parasitic upon many species of salt-water fish. When the final host animals eat paratenic hosts, the larvae grow to adulthood in the hosts' stomach. However, when hu mans eat these infested fish, the larvae die instead, causing a disease called anisakiasis. In 1960, in the Netherlands, van Thiel et al. found a worm in the intestinal wall of a patient who had eaten raw herring and had suffered symptoms of acute abdomen. The impact of this report was tremendous among Japanese parasitologists because of the Japanese habit of eating raw fish. In 1964, the Special Research Group from the Ministry of Education was established to investigate the disease, stimulating progress in the study of anisakiasis. Three types of worm, Anisakis simplex larva (previously known as Anisakis larva type I), Anisakis physeteris larva (Anisakis larva type II), and Pseudoterranova decipiens larva type A, are believed to cause anisakiasis. As many as 165 kinds of fish and squid in the seas near Japan are hosts to Anisakis simplex, and 9 species are hosts to Pseudoterranova decipiens larvae. Contra caecum has experimentally been observed to invade the gastrointestinal tract, but no infection by this larva has been reported in humans. A case of infection by Pseudoterranova decipiens type B has been described. In Japan, the name Terranova decipiens (Shiraki 1974) has been adopted instead of Phocanema decipiens (Mozgovoi 1953)."

Part I The Nano-Scale Biological Systems in Nature; Molecular bio-motors in living cells - by T. Nishizaka; The form designed by viral genome - by K. Onodera; Part II Detection and Characterization Technology; Atomic force microscopy applied to nano-mechanics of the cell - by A. Ikai; Design, synthesis and biological application of fluorescent sensor molecules for cellular imaging - by K. Kikuchi; Dynamic visualization of cellular signaling - by Q. Ni and J. Zhang; Part III Fabrication Technology; Surface acoustic wave atomizer and electrostatic deposition - by Y. Yamagata; Electrospray deposition of biomolecules by V.N. Morozov; Part IV Processing Technology; Droplet handling - by T.Torii; Integrated microfluidic systems - by S. Kaneda and T. Fujii; Part V Applications; A novel non-viral gene delivery system: Multifunctional envelope-type nano device - by H. Hatakeyama, H. Akita, K. Kogure, and H. Harashima; Biosensors - by M. Saito, H.M. Hiep, N. Nagatani, and E.Tamiya; Micro bioreactors - by Sato and T. Kitamori

For the first time a compilation of chapters that depict the biological bases underlying the development of lentiviral vectors, the techniques involved in the manufacture of this new gene delivery tool, and its most promising applications.

During the late 1970's the application of hybridoma technology led to an explosion in the discovery and characterization of proteins expressed at the surface of hematopoietic cells. The understanding of T lymphocyte biology benefited enormously from this advance and from newly developed techniques for obtaining clonal T cells. Application of these methodologies resulted in the identification of the clonally restricted T cell antigen receptors (TCRs) and of a number of other molecules expressed more broadly on T cells. Among these, the CD4 and CD8 glycoproteins stood out because they were differentially expressed on distinct functional subsets of T lymphocytes. Moreover, blocking studies with monoclonal antibodies sug gested a functional role for CD4 and CD8 in T cell responses to antigen. Shortly thereafter, it was shown that T helper cells were the primary targets for the human immunodeficiency virus (HIV) and that CD4 serves as the viral receptor on these cells. These findings fueled an intense interest in CD4 during the last decade, in the hope that understanding the molecular nature of the HIV-CD4 interaction could hold the key to controlling AIDS.