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The history of the discovery of viruses by Ivanovsky, Beijerinck, and Loeffler at the end of the nineteenth century is briefly summarized. When tobacco mosaic virus was crystallized by Stanley in 1935, viruses became fascinating entities because they were viewed as living chemicals that possess the ability to reproduce. The question of whether or not viruses should be regarded as living microorganisms is discussed at length. In order to answer this question, it is necessary to clarify the nature of living systems and organisms. Once this is done, it becomes clear that viruses, although they are biological systems, are not living microorganisms. They do not possess many of the essential attributes of living organisms such as the ability to capture and store free energy and they lack the characteristic autonomy that arises from the presence of integrated, metabolic activities. Viruses do not self-replicate themselves but are being replicated through the metabolic activities of the cells they have infected. A virus becomes part of a living system only after its genome has been integrated into an infected host cell, and it is no more alive than cellular constituents such as genes, organelles, and various macromolecules.

The role played by studies of tobacco mosaic virus (TMV) in the development of virology is summarized. TMV was the first virus shown to be able to pass through a bacteria-retaining filter; it was also the first virus to be crystallized, to have its morphology and structure elucidated and its coat protein sequenced. Experiments done with TMV RNA in the 1950s established that viral nucleic acid is the carrier of viral infectivity. The mechanism of self-assembly and disassembly of TMV particles is described and the antigenic properties of virions and dissociated coat protein subunits are discussed. Studies of TMV have also led to various biotechnological applications which are briefly described.

Antigenicity or antigenic reactivity refers to the capacity of viruses to bind to specific antibody molecules. The antigenicity of nonenveloped viruses resides in the antigenic sites or B-cell epitopes of capsid proteins that are recognized by the binding sites of antibodies. Protein epitopes are classified as either continuous or discontinuous depending on whether the amino acids included in the epitope are contiguous in the polypeptide chain or not. Most epitopes are discontinuous and since they consist of surface residues brought together by the folding of the peptide chain, their antigenic reactivity depends on the native conformation of the protein. The quaternary structure of viral capsids gives rise to epitopes known as neotopes. Neotopes arise either through conformational changes in the capsid proteins induced by intersubunit interactions or by the juxtaposition of residues from neighboring subunits forming a novel epitope. Immunogenicity is the ability of a protein to give rise to an immune response in a competent host and it can be defined only in the biological context of the host. Knowledge of the viral antigenic sites recognized by antibodies does not necessarily indicate which immunogenic structure initiated the production of antibodies in the immunized host. Failure to differentiate between antigenicity and immunogenicity is responsible for the lack of success in developing synthetic peptide vaccines against viral diseases.

More than a dozen antigenic determinants have been localized in histones by measuring the antigenic activity of natural and synthetic fragments of the molecules, using antisera raised against the histones or synthetic peptides of the histones as well as monoclonal antibodies obtained from autoimmune mice. Six of the eight chain termini of the four core histones were found to be antigenically active. Our increasing knowledge of the location of antigenic determinants in histones makes it possible to use the corresponding antibodies for studying the topography of chromatin subunits as well as functional aspects of chromatin.

The fine specificity of monoclonal antibodies for different residues of cyclosporine (Cs) has been studied. The results indicate that the conformation of Cs in aqueous medium corresponds to that observed in crystals rather than that found in aprotic solvents.

Publisher Summary The accelerated development of serological studies on plant viruses during the past ten years can be followed easily by simply counting the number of viruses that have proved amenable to serological testing. This steady increase partly reflects the widening applicability and improvements of virus purification methods and seems to allow the generalization that eventually antisera will become available to all the mechanically transmissible plant viruses, whose nucleic acid is protected by a protein coat. This increasing popularity of serological studies seems also to have followed closely upon the development of immunodiffusion techniques that have greatly facilitated serological work. Most of the early immunological studies on plant viruses were performed by the laborious precipitin reaction in free liquid. Improvements in virus purification methods, the production of high-tittered antisera and their use in virus classification, the widening acceptance of serological criteria in virus nomenclature, and the use of plant viruses as models for the study of some of the unsolved riddles of immunochemistry. The most commonly used serological test in plant virology is without question the precipitin reaction. Gel precipitin tests are less laborious than those in free liquid, they require less antiserum, and provide more information on the homogeneity and purity of the reactants and on the size of and relationships among antigens. Two main groups of gel diffusion serological methods are usually distinguished: simple (or single) diffusion techniques where only one of the reactants, usually the antigen, is diffusing into a gel containing the other reactant, and double diffusion techniques where both reactants are diffusing into a gel initially free of them. Each group of techniques can be further divided into diffusion in one dimension and diffusion in two dimensions, depending on whether the reactions are carried out in tubes or in plates.

Mention d'édition : 3rd ed.; International audience; Birnaviruses and picobirnaviruses form two distinct families of double-stranded (ds) RNA viruses. The unique common feature linking birna- and picobirnaviruses is the bisegmented nature of their genome. In this article, recent advances in the characterization of these viruses are presented. The atomic structures of the capsid protein and of the RNA-dependent RNA polymerase (RdRp) of an avian birnavirus have recently been determined. The capsid protein was found to possess homologies to the capsid protein of positive-strand RNA viruses, like the nodaviruses, and to the T = 13 capsid protein of members of the family Reoviridae of dsRNA viruses. The RdRp was shown to share a unique C-A-B motif arrangement in the palm subdomain also identified in two insect positive-strand RNA viruses. These two features suggest the possible emergence of the birnaviruses from a positive-strand RNA virus ancestor. Furthermore, the viral protease that displays a catalytic serine/lysine dyad has a fold similar to the one of the bacterial proteases Lon suggesting that this virus lineage may have captured a eukaryotic protease Lon homolog during evolution. Picobirnaviruses possess a conventional RdRp. They probably do not represent an intermediate in the birnavirus emergence from a positive-strand RNA virus.

For a long time, the viral world has been divided in two apparently unrelated groups: bacteriophages and eukaryotic viruses. Indeed, viruses were thought to have originated from genetic material derived from their respective host cells. Several recent findings have concurred to reevaluate this assumption. Comparative analysis of 16S/18S rRNA has first replaced the prokaryote/eukaryote dichotomy by a division of the living world into three cellular domains: Archaea, Bacteria, and Eukarya. Then, it has been found that viruses infecting hosts from different domains can share homologous traits (e.g., capsid proteins), otherwise unknown in the cellular world. Comparative genomics has shown that most viral proteins have no cellular homologs, also suggesting the existence of an ancient and extremely diverse viral world that always coexisted and possibly predated the world of modern cells. This has prompted new hypotheses on the origin of viruses. It has been suggested that viruses could have originated either before the appearance of cells (using self-replicating macromolecules as the first hosts) or from ancient RNA or DNA cells (by parasitic reduction or from escaped genomic material). In these scenarios, it has been speculated that viruses have played important roles in the origin of modern cells, either as inventors of DNA, and/or as progenitors of the eukaryotic nucleus.