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

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Abstract
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 3H‐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 3H‐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 T1 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· (br5C)n, or a sulfur at C‐2, (I)n· (s2C)n, were not inactivated in the presence of 50% human plasma (or serum).