The Influence of Host Resistance on Virus Infectivity as Exemplified with Bacteriophage

Parker (1) has shown that the results of infectivity measurements with vaccinia virus may be interpreted as a Poisson distribution of single infective particles among aliquots of the virus obtained by dilution. Thus, if it may be assumed that there exists a quanti ty of virus invariably necessary and invariably sufficient to produce a lesion in the skin of the rabbit, the behavior on dilution requires this quanti ty to be a single indivisible particle. However, if the possibility exists that some independently varying factor influences the appearance of lesions in the inoculated sites, the Poisson distribution is inapplicable, and a different conclusion is reached. In this case the results can only be interpreted as an indication of a particular kind of dose response among the animals tested. Bryan and Beard (2) have called attention to the fact that the single particle response curve has considerable resemblance to the hyperbolic curves characteristic of certain drugs (per cent of positive responses plotted against dosage). Their discussion gives the impression that the reverse is also necessarily true. Actually, two separate requirements must be met if the response to a drug is to resemble the response to single infective particles. First, the distribution of resistance among the animals must be of the extreme skew type, resulting in an approximately symmetrical distribution of logarithms of individual effective doses. In addition, the dispersion of these doses must have a particular value, e.g. the ratio between the dose affecting 64 per cent of the population and the dose affecting 16 per cent must be 10.6. Gaddum (3) has collected data for a number of drugs fulfilling the first of these two requirements. In his Table I, twenty-five examples are cited, together with the dispersion measures obtained. The latter are expressed as the standard deviation of the logarithms of individual effective doses, which, for the single particle response curve, is approximately 1⁄2 log 10.6 or 0.51. The values tabulated for the twenty-five measurements fall between 0.04 and 7o3