INHIBITION OF REOVIRUS-STIMULATED MURINE NATURAL-KILLER-CELL CYTOTOXICITY BY CYCLOSPORINE

Reovirus type 3 is a double-stranded RNA virus that is a potent induce r of murine natural killer (NK) cell cytotoxicity, most likely as a re sult of virus-induced interferon production. We determined that reovir us was an effective inducer of high levels of NK cytotoxicity. A singl e injection of cyclosporine (CS), administered concurrently with reovi rus or delayed until three days after injecting CS, significantly inhi bited NK cytotoxicity. CS significantly suppressed reovirus-induced NK cytotoxicity when added directly to the chromium-release assay. We de termined that CS inhibited the ability of murine spleen cells to form conjugates with YAC-1 tumor target cells. Finally, CS was shown to dir ectly inhibit reovirus replication in vitro. Our results demonstrate t hat CS is an effective inhibitor of reovirus-induced NK cytotoxicity a nd suggest that inhibition occurs through multiple mechanisms includin g direct effects on the NK cells and direct inhibition of virus replic ation.