Biochemical studies of virus-infected cells.

The orientation imposed by the subject of this monograph leads us to emphasize those aspects of the chemistry of infection that may serve our understanding of the morphology of infection. Indeed, much of the effort expended in this field has been justified under a hypothesis that the genesis of the cytopathic effect is a biochemical lesion. How that lesion is inflicted by the virus, the ensuing chain of secondary reactions, and the translation of molecular alterations to macrochanges, together, comprise the scope of our interest. Other papers in this monograph, while representing impressive advances, also express pre-eminently how incompletely the metabolic and morphologic effects of any viral infection can be described. Despite this, it may be well to sketch, in general terms, the over-all pattern as it appears in the light of present observations. In assuming the task, it is realized that the inevitable reward for any error proved upon me can only be the further advancement of virology. A profitable consideration of the chemistry of viral infection as distinct from the chemistry of the virus has waited upon developments in tissue culture that allow, first of all, the important separation of the primary cytopathology from the inflammatory and proliferative effects of a secondary nature. An equally important result of the tissue culture technique is the ability to observe changes most easily by comparison of infected and normal cultures where, because of the completeness of infection, one is really comparing normal and infected cells. Only preliminary studies of the rate and nature of the initiation of infection allow one to proceed with assurance in this regard. A variety of techniques is available to limit the infection in a particular culture to a single sequence. This is an essential for the correlation of viral synthesis with the observed cellular changes and for the determination of the natural order of these processes. If classic methods of biochemistry are to be employed, the use of mass cultures becomes mandatory and of greater value where infection is initiated synchronously in all cells, since this provides for interpretation at the cellular level. The few results already available emphasize the value of complete time studies during the infectious cycle if we are to have confidence that important observations are not overlooked. Thus, with present techniques it is possible to direct our observations to very uniform multicellular cultures in which nearly every cell is undergoing a single cycle of infection in an almost synchronous manner. However, what is desired are cultures in which all cells during their growth cycle are performing physiological and biochemical activities synchronously. Also prerequisite to a determination of effects whose cause is viral is a clear notion of the properties of the normal cell; these properties must be definable and measurable. Inductive or stimulatory effects are best considered in resting cell systems