Characterization of an antiviral agent from primary murine fibroblast cultures: murine tissue culture CVI.

We have previously described a class of virus inhibitors which are produced spontaneously by many types of cells in culture and present in a number of physiological fluids. These inhibitors are differentiated from all other known naturally occurring antiviral substances in regard to their (i) lack of species specificity, (ii) broad antiviral activity (iii) absence of high affinity binding by the inhibitor to the virus, (iv) mechanism of the action of the inhibitor is through inhibition of viral attachment, and (v) extreme thermal stability. In this report, we show that this class of inhibitors can be divided into two distinct subclasses. The first category includes the inhibitor spontaneously produced by cells in culture, originally described as contact-blocking viral inhibitor (CVI), and has a polypeptide component associated with its antiviral activity. The second category includes the inhibitors detected in body fluids and tissue extracts and has no essential peptide structure. Further characterization of CVI with respect to molecular size and stability to heat and a number of chemical reagents and enzymes indicate that the antiviral activity of CVI is associated with a large molecule (90s or approximately 4 million daltons), is stable at 100(8)C, and is resistant to the action of RNase, DNase, sulfhydral reagents, protein denaturants, and extraction by organic solvents.