Enhanced Susceptibility of Virus-Infected Fibroblasts to Cytostasis Mediated by Peritoneal Exudate Cells

Abstract Murine (BALB/c) starch-induced adherent peritoneal exudate cells (PEC) exert a cytostatic effect on various tissue culture cell lines. The cytostatic activity resides in the adherent cell fraction of the PEC that, after 24 hr in culture, is devoid of T and B lymphocytes. No significant difference in the degree of inhibition of incorporation of DNA precursors upon interaction with PEC could be detected with transformed cell lines, virus-infected non-transformed cell lines, and their normal counterparts as targets. Recently explanted embryo fibroblasts are relatively resistant to PEC-mediated cytostasis. Upon in vitro transformation with the murine sarcoma virus murine leukemia virus mixture (MuSV/MuLV), the targets become more susceptible to PEC-mediated cytostasis. Infection with the nontransforming virus MuLV leads to a similar increase in susceptibility. The same pattern of differential susceptibility was obtained with embryo fibroblasts from four different strains of mice, indicating that there is no requirement for H-2 compatibility between effector and target cells. No PEC-specific 51Cr release could be detected during the 24 hr of effector-target cell interaction, indicating that the effect involves primarily cytostasis. Embryo fibroblasts infected with Sendai virus or influenza virus were also remarkably sensitized toward PEC-mediated cytostasis. The fact that inactivated Sendai virus is as active in sensitizing the targets as the active virus suggests that primary membrane reorganization events that follow virus adsorption may be a sufficient perturbation leading to enhanced susceptibility. Rat and hamster embryo fibroblasts show the same pattern of enhanced susceptibility upon interaction with inactive Sendai virus. Judged from indirect radioimmunoassay of adsorption of anti-type-C viral antigen sera, BALB/c embryo fibroblasts did not exhibit surface type-C virus specific antigens, nor did infection with the Sendai or influenza viruses induce activation of endogenous type-C viruses. The above suggests that transformation and a major alteration in the growth pattern of cells are not a prerequisite for the enhanced susceptibility of embryo fibroblasts to PEC-mediated cytostasis; rather, that membrane perturbations introduced by nontransforming unrelated viruses provide a sufficient change rendering the cells more prone to cytostasis.