In considering the intraceUular parasitism that characterizes the host-virus relationship, it has often been tacitly assumed that the parasitization of an individual host cell is limited to infection by a single virus. In contradiction to this belief, however, we have reported experiments (1) in which the cells of a Virus-induced tumor, Shope's rabbit papilloma (2), and of a carcinoma of the sort that frequently succeeds the benign growths (3, 4), were superinfected by other viruses--"superinfected" in the case of the papilloma because its cells contained the causative virus. These same studies, furthermore, included certain instances in which the simultaneous introduction of two viruses for the purpose of inducing superinfection was followed by evidence of the simultaneous activity of both of the viruses within individual cells. This evidence was the presence of two diagnostically significant inclusion bodies, the one cytoplasmic, the other intranuclear, within a single cell. In making our first report, we recognized that the histopathological examination of a stratified epithelial structure, such as the rabbit papilloma, involved the likelihood of error--of the mistaken interpretation that two overlying cells constituted a single cell. If such an error were made, the conclusion might be reached that the two inclusion bodies, cytoplasmic and intranuclear, were present in a single cell, when one of the inclusion bodies might actually be in one host cell and the other inclusion body in an overlying cell. It was for the purpose of eliminating, as far as possible, this opportunity for error that the present investigation was undertaken. The results of these experiments (5), which will now be described in detail, give evidence that an individual host cell can be simultaneously parasitized by more than one virus and amply confirm our earlier findings.
Materials and MethodsThe five viruses employed in the present investigations were vaccinia, myxoma virus, B virus, herpes virus, and virus III. The strains of virus employed, and the method for the preparation of the virus suspensions have already been described in detail (1 ¢).Normal host cells for experimental infection were provided by using rabbit's cornea, akin, or testicle. Of the eleven rabbits employed, nine were domestic stock rabbits (Oryctolagus)