Viruses - Böcker

It is now just 20 years since Gomatos and his co-workers at the Rocke­ feller University showed that the nucleic acid in reovirus particles is double-stranded RNA (dsRNA). This discovery created great excitement, for dsRNA was at that time under intense investigation as the replicative form of viral genomes consisting of single-stranded RNA. An equally interesting and important finding followed soon after: it was found that the reovirus genome consists, not of a single nucleic acid molecule, but of 10 discrete "segments," each with its specific sequence content and each transcribed into its own messenger RNA. It is clear now that these segments are genes. Not surprisingly, the availability of a viral genome 10 unlinked genes has permitted some unique lines of in­ consisting of vestigation in molecular biology. Mammalian and avian reoviruses proved to be but the first of several viruses recognized as sharing Similarity in size and morphology and ge­ nomes consisting of 10, II, or 12 separate genes. These viruses are dis­ tributed throughout living organisms; among the natural hosts of mem­ bers of this virus family are vertebrates, Insects, and plants. Members of the Reoviridae family differ widely in the virulence that they exhibit toward their hosts . . For example, the first discovered mam­ malian reovirus literally is, as the name signifies, a "respiratory enteric orphan" virus, that is, a virus unassociated with disease.

In this second volume in the series The Retroviridae, the readers are treated to up-to-date reviews on these viruses, which are found in a variety of animal species. The volume begins with important observations on the general fea­ tures of retrovirus entry into cells as determined by the viral envelope glyco­ proteins and the cell surface receptors (Chapter 1). Aspects of this virus-cell interaction form the basis for the variety of biologic effects associated with this virus family. A timely review of the oncogenic feline viruses is included next (Chapter 2). These viruses, along with the avian and murine retroviruses (Volume 1, Chapters 6 and 7), have provided valuable insight into cancer induction in other animal species, including humans. Two other major groups of retroviruses, the lentiviruses and the spuma­ viruses, are introduced in the present volume. Initially these groups, along with oncoviruses, were the three subfamilies in the Retroviridae. This com­ plex virus family has now been reclassified into seven separate genera (Vol­ ume 1, Chapter 2). Equine infectious anemia virus is the prototype for a lentivirus (Chapter 5). One of the first viruses discovered in nature (1904), it was only relatively recently recognized as a retrovirus. Lentiviruses are asso­ ciated primarily with immunologic disorders such as autoimmunity and AIDS (Chapters 3-5), but their association with neurologic disease is also well established (Chapters 4 and 5, and future volumes).

The books in this acclaimed series are the most detailed, up-to-date accounts of the field available. Volume 3 explores the oncogenic potential shared by retroviruses of different species, the widespread presence of retrovirues in nature, and the role of retroviruses in normal development and pathogenesis.

Coronaviruses were recognized as a group of enveloped, RNA viruses in 1968 and accepted by the International Committee on the Taxonomy of Viruses as a separate family, the Coronaviridae, in 1975. By 1978, it had become evident that the coronavirus genomic RNA was infectious (i. e. , positive strand), and by 1983, at least the framework of the coronavirus replication strategy had been per­ ceived. Subsequently, with the application of recombinant DNA techniques, there have been remarkable advances in our understanding of the molecular biology of coronaviruses, and a mass of structural data concerning coronavirus genomes, mRNAs, and pro teins now exists. More recently, attention has been focused on the role of essential and accessory gene products in the coronavirus replication cyde and a molecular analysis of the structure-function relation­ ships of coronavirus proteins. Nevertheless, there are still large gaps in our knowledge, for instance, in areas such as the genesis of coronavirus subgenomic mRNAs or the function of the coronavirus RNA-dependent RNA polymerase. The diseases caused by coronaviruses have been known for much longer than the agents themselves. Possibly the first coronavirus-related disease to be recorded was feline infectious peritonitis, as early as 1912. The diseases associ­ ated with infectious bronchitis virus, transmissible gastroenteritis virus, and murine hepatitis virus were all well known before 1950.

depth overview of the retrovirus family. I have greatly enjoyed and learned from this experience. Each chapter is an excellent introduction to the topic covered and provides a good foundation for further work in the field. Jay A. Levy University of California School of Medicine San Francisco, California REFERENCES Brown, E. W., Yuhki, N., Packer, C., and O'Brien, S. J., 1994, A lion lentivirus related to feline immunodeficiency virus: Epidemiologic and phylogenetic aspects, ,. Viral. 68:5953-5968. Merza, M., Larsson, E., Steen, M., and Morein, B., 1994, Association of a retrovirus with a wasting condition in the Swedish moose, Virology 202:956-961. Contents Chapter 1 The Human Immunodeficiency Viruses Edward Barker, Susan W Barnett, Leonidas Stamatatos, and Jay A. Levy I. Introduction .................................................... 1 TI. Description of Agent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 A. Virus Structure .............................................. 2 B. Genetic Organization and Gene Function ...................... 2 TIL Transmission.................................................... 7 A. General Observations ........................................ 7 B. HIV Transmission by Blood and Blood Products ................ 8 C. HIV Transmission by Genital Fluids ........................... 10 D. HIV Transmission by Other Body Fluids ....................... 12 E. Mother-to-Child Transmission ................................ 12 IV. HIV Infection of the Cell . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 . . . . . . . . . . . . . A. Introduction ................................................. 13 B. HIV-Cell Interaction............ ............... .............. 15 C. CD4-Induced gp120 Conformational Changes .................. 16 D. Soluble CD4-Induced gp120-gp41 Dissociation..... ............ 16 E. gp120 Proteolytic Cleavage ................................... 17 F. pH-Independent Membrane Fusion ............................ 19 G. Transmission of HIV by Cell-to-Cell Fusion.................... 19 H. Additional Cell Surface Receptors for HIV ..................... 20 I. The Envelope Region and Cell Tropism ........ . . . . . . . . . . . . 21 . . . .

In this comprehensive reference, leading researchers examine the biology, molecular biology, and diseases of the Bunyaviridae, and provide up-to-date information on the genetic characterization and variations of this virus group. The chapters deal with the molecular biology of five genera: Bunyavirus, Hantavirus, Nairovirus, Phlebovirus, and Tospovirus. The chapters examine Bunyaviridae assembly and intracelluar protein transport as well as Bunyaviridae genetics. The contributors discuss the Bunyaviridae diseases, including the hantavirus pulmonary syndrome.

This fifth volume in the series The Plant Viruses, dealing with viruses with bipartite genomes, completes the coverage of viruses with isometric parti­ cles and genomes consisting of single-stranded, positive-sense RNA: viruses that have tripartite and monopartite genomes of this kind were dealt with in Volumes 1 and 3, respectively. How close are the affinities among the viruses within the groupings distinguished in this way? All those with tripartite genomes are considered to be sufficiently closely related to be included in the family Bromoviridae, whereas the monopartite-genome viruses covered in Volume 3 clearly are a much more diverse collection. Affinities among the viruses with bipartite genomes are considered in Chapter 1 of this volume, along with the possible origins, advantages, and disadvantages of these ge­ nomes. The conclusion reached from this assessment is that the bipartite­ genome viruses fall into four categories, those within each category having closer affinities with viruses not included in this book than with viruses in the other categories. No evidence was found that possession of a bipartite genome gives a virus overwhelming advantages over viruses of other sorts. More probably, any advantages are largely balanced by disadvantages, and bipartite genomes may be best considered simply as an alternative design for the hereditary material of a virus.

The past decade has witnessed an explosion of information on the molecular biology of insect viruses and a frenzy of activity in applying this information to medicine and agriculture. Genetically engineered baculoviruses are presently being tested for commercial use as pesticides, and the study of such viruses is also revealing remarkable insights into basic cellular processes such as apoptosis. This comprehensive volume provides readers with knowledge of basic and applied baculovirology so that current literature in the field can be appreciated.

This book focuses on those virus families that are found primarily or exclusively in insects, covering all major families of insect-selective viruses except for the baculoviruses which were described in a previous volume of "The Viruses" series. The topics include: the large DNA viruses; the small DNA densoviruses; the RNA viruses; and, the arbovirus expression systems and their potential employment in the future. Ninety-eight illustrations supplement the text.

Influenza virus is an important human pathogen, frequently causing widespread disease and a significant loss of life. Much has been learned about the structure of the virus, its genetic variation, its mode of gene expression and replication, and its interaction with the host immu­ nologic system. This knowledge has the potential of leading to ap­ proaches for the control of influenza virus. In addition, research on influ­ enza virus has led to important advances in eukaryotic molecular and cellular biology and in immunology. A major focus of this book is the molecular biology of influenza virus. The first chapter, which serves as an introduction, describes the structure of each of the genomic RNA segments and their encoded pro­ teins. The second chapter discusses the molecular mechanisms involved in the expression and replication of the viral genome. In addition to other subjects, this chapter deals with one of the most distinctive features of influenza virus, namely the unique mechanism whereby viral messenger RNA synthesis is initiated by primers deaved from newly synthesized host-cell RNAs in the nudeus. Among the most significant accomplish­ ments in influenza virus research has been the delineation of the three­ dimensional structure of the two surface glycoproteins of the virus, the hemagglutinin and neuraminidase. This has provided a structural basis for mapping both the antigenic sites and the regions involved in the major biological functions of these two molecules.

More than seven years have passed since the first monograph on viroids was published. At that time, the existence of viroids as a novel type of pathogen far smaller than viruses had been amply demonstrated and some of their unusual molecular properties had been elucidated, but the entry of molecular biology into viroid research was still in its infancy. Since that time, our knowledge of the molecular properties of viroids has increased exponentially and viroids have become even more fasci­ nating than was the case seven years ago. Today, aside from transfer RNA, viroids are probably the best known type of RNA-at least from a struc­ tural standpoint. Much less is known of the mechanisms of viroid func­ tion, such as the exact pathway and enzymology of viroid replication and the biochemistry of viroid pathogenesis. Recently, however, emphasis in viroid research has shifted from structural to functional themes and im­ portant beginnings have been made in the elucidation of viroid struc­ ture-function relationships. With the discovery of viroidlike RNAs within the capsids of certain plant viruses and the finding of surprising structural similarities between viroids and plant satellite RNAs, the conceptual gap between viroids and conventional viruses has significantly narrowed. Even beyond virology, connecting links with cellular RNAs have come to light and the long isolation of viroids land "viroidologists"J has come to an end.

It has been more than twenty years since the isolation of polyoma virus and SV40, and the reports that they could produce tumors in animals and transformation of cells in culture. What was startling was that these biologic properties are associated with viruses that contain genetic in­ formation that is able to code for only five or six proteins. Since that time, investigations with these viruses have been in four principal areas. One major area of study has been on cells transformed by viruses that show altered growth properties and specify new viral and cellular proteins. Transformation studies have focused on the tumor (T) antigens that are specified by the virus and are required to initiate and to maintain the transformed state. Current studies on transformation are summarized in Chapter 4. The second broad area of investigation concerns replication of viruses during a lytic cycle of infection. T-antigens that are the hallmark of transformed cells are also expressed in cells that are lytically infected and are required for viral DNA replication and also function to alter rates of transcription of the early and late viral genes. Except for T-antigen, virus replication depends on the cellular enzymatic machinery and so the description of viral macromolecular synthesis has provided valuable insights into the cellular biosynthetic pathways. These studies are described in Chapters 1-3. The studies that have medical relevance concern JC and BK viruses and there is evidence of widespread exposure of human populations to these agents.

During the past two decades, virus taxonomy has advanced to the point where most viruses can be classified as belonging to families, genera, or groups of related viruses. Virus classification is primarily based on chem­ ical and physical similarities, such as the size and shape of the virion, the nature of the genomic nucleic acid, the number and function of com­ ponent proteins, the presence of lipids and of additional structural fea­ tures, such as envelopes, and serological interrelationships. The families, genera, or groups of viruses that have been defined on the basis of such criteria by the International Committee on Taxonomy of Viruses (ICTV) will be described in some detail in this catalogue and illustrated by elec­ tron micrographs. In my present attempt to list most if not all well es­ tablished and studied viruses in alphabetical order, I have largely confined myself to identifying them only in such taxonomic terms, generally without quoting specific data reported for individual viruses. If the latter data do not at times agree closely with those given for the taxon or group, it is difficult to decide to what extent this is attributable to misclassi­ fication due to insufficient data and errors in the analytical procedures and descriptions, or to what extent this is an expression of Nature's free­ dom of choice and abhorrence of restrictive classifications.

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.

In this volume, a distinguished international group of contributors present the latest molecular, organismal, and epidemiological research on arenaviruses. Their work will broaden both the clinician's and the researcher's knowledge of basic mechanisms of immunological tolerance, viral immunosuppression, the nature of protective immune responses to vaccination, and viral effects on cell functions.

What justifies the size of this compendium of reviews on the paramyxoviruses? As intracellular parasites that reproduce with almost complete indifference to nuclear activities, paramyxoviruses have not been providing insights about genes that regulate cellular activities and development, topics that account for much of the excitement in modem biology. For contributions of virus research to those topics, we must look to the retroviruses, which have the propensity to steal developmentally important genes and subvert them to malignant pur­ poses, and to the nuclear DNA viruses, whose gene expression depends heavily upon cellular transcription machinery, making them exceptionally useful tools for identifying and characterizing components of that machinery. From this perspective, it may appear that purely lytic viruses like the paramyxoviruses are sitting on the sidelines of contemporary biology. But there is plenty of action on the sidelines. Paramyxoviruses remain unconquered, devastating agents of disease. Human deaths attributable to paramyxoviruses worldwide, especially in children, are numbered in the mil­ lions annually. There are many pathogenic paramyxoviruses and too few effec­ tive vaccines, and those vaccines (against measles and mumps) are affordable only by relatively affluent nations. Moreover, the paramyxoviruses are intrin­ sically interesting organisms, presenting the challenge of understanding the self-replication of RNA and many other challenges peculiar to the structures and functions of their proteins, not only as individual entities, but also as they act in concert during virus reproduction and interact with vital functions of the cells they infect and often (but not always) destroy.

There are over a million different species of insects, and individually they 8 outnumber humans by more than 10 to 1. Moreover, some insects live in close association with both plants and higher animals and naturally exchange viruses with them. It has even been speculated that viruses in general may have radiated through the plant and animal kingdoms from common insect origins. Be that as it may, since insects play pivotal roles in the biosphere, both to the benefit and detriment of mankind, they and the viruses that infect them are important subjects for study. Insects are infected by a diverse medley of viruses, and this volume focuses on those insect virus families that are found primarily or exclusively in insects. All major families of insect-selective viruses are covered except for the baculo­ viruses, which were described in a separate volume of The Viruses series. Included in this volume are the established families of insect viruses, the newly recognized ascovirus family, and the nudiviruses, which probably represent a separate family but currently remain unclassified. The coverage of arboviruses is limited to a single chapter that focuses on their potential utility as vectors and in insect control. Omitted for practical reasons are several individual insect viruses that have been described sporadically in the literature and probably represent novel virus families.

'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.

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.

It has been known for a long time that the majority of plant viruses contain RNA and in the past decade and a half it has been realized that many have genomes consisting of three molecules of single-stranded RNA with positive polarity. Among these are viruses belonging to four groups recognized by the International Committee for Virus Taxonomy: the Bromovirus and Cucumovirus groups whose genomes are encapsi­ dated in small icosahedral particles or the Ilarvirus and alfalfa mosaic virus groups with spheroidal or bacilliform particles. In addition to their tripartite genomes, these viruses share a number of other properties and it has been proposed that they should perhaps be grouped in a single virus family for which the name Tricornaviridae has been suggested, the tri indicating the tripartite nature of the genome, the co emphasizing the cooperation of the three genome parts required to initiate infection, and the rna indicating that the genome is composed of RNA. Viruses of this "family" are less uniform in their biological proper­ ties. A number of them are widespread, causing very destructive plant diseases. Viruses such as those of cucumber mosaic and alfalfa mosaic have very extensive host ranges and are responsible for serious crop losses in many parts of the world. Others such as prunus necrotic ringspot or prune dwarf viruses are more restricted in their host ranges but never­ theless infect important perennial hosts such as stone fruits and reduce productivity considerably.

It has been 10 years since Plenum included a series of reviews on bacte­ riophages, in Comprehensive Virology. Chapters in that series contained physical-genetic maps but very little DNA sequence information. Now the complete DNA sequence is known for some phages, and the se­ quences for others will soon follow. During the past 10 years two phages have come into common use as reagents: A phage for cloning single copies of genes, and Ml3 for cloning and DNA sequencing by the dideoxy termi­ nation method. Also during that period the use of alternative sigma fac­ tors by RNA polymerase has become established for SPOl and T4. This seems to be a widely used mechanism in bacteria, since it has been implicated in sporulation, heat shock response, and regulation of nitro­ gen metabolism. The control of transcription by the binding of A phage CII protein to the -35 region of the promoter is a recent finding, and it is not known how widespread this mechanism may be. This rapid progress made me eager to solicit a new series of reviews. These contributions are of two types. Each of the first type deals with an issue that is exemplified by many kinds of phages; chapters of this type should be useful in teaching advanced courses. Chapters of the second type provide comprehensive pictures of individual phage families and should provide valuable information for use in planning experiments.

It has been 10 years since the Plenum Publishing Corporation printed a series of review articles on bacteriophages in Comprehensive Virology. Articles in that series contained physical-genetic maps but very little DNA sequence information. Now the complete DNA sequence is known for some phages, and others will soon follow. During the past 10 years, two phages have come into common use as reagents: A phage for cloning single copies of genes, and M13 for cloning and DNA sequencing by the dideoxy termination method. Also during this period the use of alter­ native sigma factors by RNA polymerase has become established for and T4. This seems to be a widely used mechanism in bacteria, SPO 1 since it has been implicated in sporulation, heat shock response, and regulation of nitrogen metabolism. The control of transcription by the binding of A phage CII protein to the -35 region of the promoter is a recent finding, and it is not known how widespread this mechanism may be. This rapid progress made me eager to solicit a new series of reviews. These chapters are of two types: each of the first type deals with an issue that is exemplified by many kinds of phages. Chapters of this type should be useful in teaching advanced courses. Chapters of the second type pro­ vide comprehensive pictures of individual phage families and should pro­ vide valuable information for use in planning experiments.

The first volume of the series entitled Comprehensive Virology was pub­ lished in 1974 and the last is yet to appear. We noted in 1974 that virology as a discipline has passed through its descriptive and phenomenological phases and was joining the molecular biology revolution. 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 mo­ lecular 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 Comprehensive Virology, some of the coverage will obviously not remain up-to-date. The usual remedy to this aspect of science publishing is to produce 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 of Compre­ hensive Virology under the titles Reproduction, Structure and Assembly, Regulation and Genetics, Additional Topics, and Virus-Host Interac­ tions. Instead we have organized a new series entitled The Viruses.

This volume of the series The Plant Viruses is devoted to viruses with rod-shaped particles belonging to the following four groups: the toba­ moviruses (named after tobacco mosaic virus), the tobraviruses (after to­ bacco rattle), the hordeiviruses (after the latin hordeum in honor of the type member barley stripe mosaic virus), and the not yet officially rec­ ognized furoviruses (fungus-transmitted rod-shaped viruses, Shirako and Brakke, 1984). At present these clusters of plant viruses are called groups instead of genera or families as is customary in other areas of virology. This pe­ culiarity of plant viral taxonomy (Matthews, 1982) is due to the fact that the current Plant Virus Subcommittee of the International Committee of Taxonomy of Viruses is deeply split on what to call the categories or ranks used in virus classification. Some plant virologists believe that the species concept cannot be applied to viruses because this concept, according to them, necessarily involves sexual reproduction and genetic isolation (Milne, 1984; Murant, 1985). This belief no doubt stems from the fact that these authors restrict the use of the term species to biological species. According to them, a collection of similar viral isolates and strains does constitute an individ­ ual virus, i. e. , it is a taxonomy entity separate from other individual viruses.

The viruses of the family Rhabdoviridae have an exceedingly broad host range and are widely distributed throughout the animal and plant king­ doms. Animal rhabdoviruses infect and often cause disease in insects, fish, and mammals, including man. The prototype rhabdovirus, vesicular stomatitis virus !VSV), has been extensively studied and provides perhaps the best model system for studying negative-strand viruses. The popularity of VSV as a model system is to a considerable extent due to its relative simplicity and to its rapid growth, generally to high titer, in many cell types ranging from yeast to human. The nucleocapsids of these viruses also carry transcriptional and replicative functions that are expressed in cell-free systems. The first RNA-dependent RNA poly­ merase was described in VSV and its G protein provided an early model system for studying the synthesis, processing, and membrane insertion of mammalian glycoproteins. VSV is also highly cytopathogenic and has been studied quite extensively for its capacity to kill cells and to shut off cellular macromolecular synthesis. Even earlier, VSV was discovered to be highly susceptible to the action of interferons and has served ever since as a means for quantitating the activity of interferons. To my way of thinking, the spark that ignited the explosion of re­ search in this field was struck at the First International Colloquium on Rhabdoviruses, attended by 30 or so participants in Roscoff, France, in June 1972.