Stimulating interaction between viruses (stimulons).

During previous investigations on the viral autoinhibition phenomenon' it was observed that interferon was detected in the culture medium of viral-infected cells but not in extracts of these cells. It was suggested that viral-infected cells may contain a substance antagonistic to interferon, a substance which, unlike interferon, diffuses poorly into the surrounding culture medium. Further studies to explore this hypothesis were complicated because of the considerable quantities of interferon produced in most of the cell-virus systems described. The recent observation in our laboratory of a "stimulating effect" on one virus by another virus permitted further investigation of this phenomenon.2' 3 A stimulating interaction between viruses can be defined in the following manner: when two or more antigenically related or unrelated viruses infect the same cell in a certain chronological order, the inducing agent stimulates the multiplication of the challenge virus. Stimulating interaction consequently represents a reverse phenomenon of the interference phenomenon as usually understood by virologists. Several hostvirus relationships of this kind have been observed and reported in the literature.20-22' 24, 29 In this report only the "stimulatinig interaction" between adenovirus 12 anld IKilham's rat virus will be presented in detail. It was postulated that this system might prove useful in the study of the hypothetical factor antagonistic to interferon, since neither adenovirus 12 nor K rat virus produce significant amnouiIts of interferon in rat cells.3 Thus the "antagonistic factor" would not be masked by the presence of initerferon. In rat cells adenovirus 12 does not induce the production of virions or even structural antigens in detectable quantities, although T antigens are formed and can be detected in the cell by the use of fluorescent antibody techniques.4 Furthermore, some of the cells in these infected cultures undergo nmaliguaiit tranisformation in vitlo.5' 6 The Kilham. rat virus induces a lytic cycle