Degradation of Poly(inosinic acid) · poly(cytidylic acid) [(I)n· (Cn)] by Human Plasma

The double‐helical RNA interferon inducer, poly(inosinic acid) · poly(cytidylic acid) [(I) n · (C) n ], is rapidly degraded by nucleases present in human plasma (serum). When incubated at 37°C with 50% human plasma, (I) n · (C) n (10 μg/ml) showed a half‐life of 6 min, [as assessed by residual acid insoluble radioactivity of an (I) n · (C) n preparation which was 3 H‐labelled in the (C) n component]. Sucrose velocity analysis revealed that human plasma nucleases specifically hydrolyzed the (C) n strand of (I) n · (C) n , as assessed with (I) n · (C) n preparations that were 3 H‐labelled in either (I) n or (C) n . The plasma nucleases that were responsible for the degradation of (I) n · (C) n resembled pancreatic ribonuclease A rather than T 1 ribonuclease in substrate specificity. (I) n · (C) n became completely inactive as an inerferon inducer when it was incubated with 50% human plasma or serum. However, its interferon‐inducing capacity was fully restored if (C) n but not (I) n was added to the host cells, after these had been exposed to the inactivated (I) n · (C) n . That the inactivating effect of human plasma on the interferon‐inducing potency of (I) n · (C) n could solely be attributed to hydrolysis of the (C) n strand was further supported by the finding that two analogues of (I) n · (C) n , which had become more resistant to degradation by pancreatic ribonuclease by virtue of some substitutions in the (C) n strand, i.e. a bromine at C‐5, (I) n · (br 5 C) n , or a sulfur at C‐2, (I) n · (s 2 C) n , were not inactivated in the presence of 50% human plasma (or serum).