Relation between the time at which cytopathic endpoint occurs in infected cultures and the initial infective virus dose, with application to the study of inhibitors of cytopathic effect

Summary

Time intervalst between infection of HeLa, ERK and MK cells and attainment of 50 per cent cytopathic endpoint have been determined for virus inoculaV of different magnitudes. Data from numerous experiments carried out with polioviruses 1, 2 and 3, coxsackieviruses A 9 and A 21, echovirus 11 and vaccinia virus, with or without virus inhibitors, statistically satisfy the regression line log(t _s −t)=n log logV+logB, wheret _s is the value oft whenV=1 TCID₅₀ unit andn andB are constants. Regression lines for an experiment with a single virus-cell system and different inhibitors pass through or near a common point. A measure of the cytopatho-genicity of the virus under the experimental conditions is given by n⁻¹.

Ifn is the slope of the regression line in the presence of an inhibitor (of viral CPE)I, possessing concentration [I] (>0), and n₀ is the slope in its absence, then then-n₀ value is shown, in the case of the three polioviruses under certain conditions, to be related to [I] by the equationn−nin0 = Q[I]^P, whereP andQ are constants. The cell protective activity (A) ofI is defined as Q^1/P.

If formation in infected cultures of substances or conditions hostile to viral multiplication does not occur until the viral TCID₅₀ approaches a specific high valueV _H , then the increase in “infective virus” in a culture corresponds to travel along an appropriate regression line (α) towards the point of intersection.