Cytocidal effect of interferons on porcine renal cells

Treatment of low-passaged pig kidney cell cultures with interferon (IFN) at greater than or equal to 80 times the limit antiviral dose resulted in death of the whole sheet within 15-30 h. This cytocidal effect was specific for both IFN and target cells. It was induced by type I IFNs from three mammalian species (human, bovine, and porcine), including electrophoretically pure HuIFN-alpha. For each IFN preparation, cytocidal and antiviral titers were closely correlated. The processus was protein synthesis dependent and was inhibited by antibodies specific for IFN. Concerning the cell counterpart, the cytocidal effect was observed on 14 different cell strains, isolated from foetal, neonate or adult pig kidneys. There was two absolute requirements for cytocidal effect to appear: (i) the cells must be of epithelioid phenotype, and (ii) the cells must be in a state of confluent monolayer. Under usual conditions of subpassaging, susceptibility to cytocidal effect was lost after 20-25 passages post-explanation, at which stage the cells acquired properties known for established pig kidney cell lines, i.e., the absence of stringent contact inhibition and a weaker sensibility to antiviral effect. An intriguing feature was that cytocidal effect developed as microplaques of dead cells rapidly enlarging to surrounding cells. Several lines of evidence render highly improbable a virus involvement in this IFN-induced plaque effect. Moreover no contaminant, like virus or mycoplasma, was found in the cell strains studied. Such an IFN-induced cytocidal activity on epithelial renal cells from porcine species provide a so far unique example of short-term lethal effect of IFNs on a normal, non lymphoid cell system.