F. Melchers

Binding of various ligands (hormones, neurotransmitters, immunological stimuli) to membrane receptors induces the following changes: 1. Receptor redistribution (clustering, "capping") 2. Conformational changes that can be detected by fluorescent probes 3. Alteration in membrane fluidity (spin label and fluorescence polarization probes) 4. Changes in fluxes of ions and metabolites 5. Increased phospholipid turnover (especially of phosphatidyl inositol) 6. Activation of membrane-bound enzymes (adenyl cyclase, ATPase, transmethylases). Some of the early changes resulting from or associated with the binding (adsorption) of virions to the host cell membrane are of the same type. Adsorption of animal viruses to cells is the ftrst step in a chain of events resulting in the production of progeny virus on the one hand and in damage to cells and tissues on the other. In the classical studies of viral infection, cells are adsorbed with virus, usually for 60 min, and the changes induced by the virus in the host cell are recorded thereafter. In the past decade, more and more studies have been aimed at the events occurring in these ftrst 60 min of the so-called adsorption period. These studies deal with the nature of adsorption, e. g. , the ligand-receptor type of interaction between the virus and the cell membrane. Many receptors for viruses were identifted and so were the viral proteins which take part in adsorption.

Several discoveries are noteworthy for allowing us to probe the recesses of the virus­ infected cell and to search for cryptic viral genomes which might provide clues in our studies of cancer etiology or developmental biology. One of the most notable was the dis­ covery of reverse transcriptase. This marked a momentous occasion in the history of molecular biology. Not only did it provide insight into the mechanism of persistence of retroviruses but it also provided us with an enzyme that could synthesize a DNA copy of any RNA. This DNA copy could then be used as a hybridization reagent to search for both complementary DNA and viral-specific RNA. Thus one could follow the course of any viral infection or probe in tumor cells for hidden viral genomes. Second, a great deal of credit must be given to the geneticists who isolated the various deletion mutants in the 'avian retrovirus system and thus provided us with the frrst means of isolating gene-spe­ cific probes. Finally, the laboratories which have mapped the genome have provided us with the framework in which to ask very specific questions with our gene-specific probes. Recently, numerous excellent reviews concerning various aspects of the retroviruses have appeared. In this review I shall not even attempt to present a comprehensive review of retroviruses.

Many of the fundamental concepts of animal virology originated from the study of the variola-cowpox-vaccinia virus system with vaccinia virus serving as the type species (Fen- nerand Burnet 1957; Burnet 1959; Fenner 1976a, b). The importance of the Poxviridae(Fen- ner 1979) for the study of viruses as biologic entities and in defIning the events which occur in virus-infected cells are exemplifIed by investigations which: (a) described the epidemiology of a virus disease in an animal population (Fenner1949, 1959b); (b) em- ployed electron microscopy to study virion structure (Peters 1956, Nagington and Home 1962, Dales and Siminovitch 1961) and to derme the morphologic stages of virion develop- ment in infected cells (Morgan et al. 1954, Dales 1963); (c) dermed and elaborated on the mechanism of nongenetic reactivation for an animal virus (Joklik et al. 1960a, Fenner and Woodroofe 1960, Hanafusa 1960); (d) described the intracellular uncoating of a viral genome (Joklik 1964a, b); (e) studied the antigenic structure and complexity of poxvirions (Loh and Riggs 1961, Woodroofe and Fenner 1962, Appleyard et al. 1964, Appleyard and Westwood 1964); (1) described the use of chemotherapy to treat viral infec- tions (Bauer et al. 1963); (g) fIrst demonstrated the presence of virion-coded enzymes encapsulated within virions (Kates and McAuslan 1967, Munyon et al. 1967); and (h) established the H -2 restriction of cytotoxic T-cell killing of virus-infected cells in the murine system (Doherty et al. 1976).