POLYADENYLIC - POLYURIDYLIC ACID-INDUCED DETERMINANTS OF HOST-RESISTANCE TO CYTOMEGALOVIRUS AND THEIR POTENTIATION BY HYPERTHERMIA

The ability of spleen cells from poly A:poly U-treated mice to inhibit murine cytomegalovirus (MCMV) replication in confluent monolayer cells of secondary mouse embryo fibroblasts (MEFs) cultured at 37 and 40-degrees-C was investigated. When spleen cells from BALB/c mice injected 48 h earlier with poly A:poly U were added to MEFs infected 2 h previously with MCMV, 37% less plaques were observed than in cultures containing control cells. Of interest, the poly A:poly U-induced antiviral activity at the elevated temperature (40-degrees-C) resulted in a further drop to 61% in MCMV-induced plaques compared to those of the normothermic (37-degrees-C) cultures. The antiviral function of spleen cells induced by poly A:poly U was evident in the supernatant fluid when cultured for 48 h at 37-degrees-C. MCMV-induced plaques were reduced to 52 and 5% of controls in the plaque assays performed at 37 and 40-degrees-C, respectively. Supernatant fluids generated at 40-degrees-C, however, inhibited MCMV replication only when incubated at 40-degrees-C. No direct inhibitory effect of the supernatant fluids on MCMV was evident; rather, inhibition was effected directly on the MEFs. The NK cell fraction of spleen cells from poly A:poly U-treated mice alone showed only a slight inhibitory effect at 40-degrees-C. However, in the presence of the supernatant fluid from poly A:poly U-exposed spleen cells, the antiviral activity of NK cells was significantly increased both at 37 and 40-degrees-C. The cellular source of the culture fluid showing poly A:poly U-induced antiviral activity appeared to be in the T-cell population. It was completely neutralized by monoclonal anti-IFN-gamma antibody but not by anti-IFN-beta, anti-IL4, anti-transforming growth factor, or anti-prostaglandin E2. In conclusion, these data document the ability of spleen cells from poly A:poly U-treated mice to inhibit MCMV replication and this activity is potentiated by hyperthermic conditions. The antiviral function of poly A:poly U-treated spleen cells appeared to be due mainly to the action of IFN-gamma produced by T cells. The enhanced antiviral activity by hyperthermia appeared to be related to the action of IFN-gamma rather than its production.