The myxoma virus M-T7 protein contains significant sequence similarity to the ligand binding domain of the mammalian interferon- receptors, and functions as a soluble homolog which can bind and inhibit the biological activities of rabbit interferon- (Upton, C., Mossman, K., and McFadden, G.(1992) Science 258: 1369-1372). M-T7, the most abundantly secreted protein from myxoma virus-infected cells, was shown to be expressed in significant biological amounts as a typical poxvirus early gene product, efficiently secreted at early times of infection to levels that exceed 5 10 molecules/cell, and function as a stable inhibitory protein in infected cell supernatants until late times of infection. M-T7 was specific in binding and inhibiting rabbit interferon-, and did not bind either human or murine interferon-. Scatchard analysis of rabbit interferon- binding curves yielded a single high affinity binding site on M-T7, with a K of 1.2 10M, which is comparable to the affinity between soluble forms of cellular interferon- receptors and their cognate ligands. In comparison, rabbit interferon- was shown to bind its cellular receptor with a K of 5.9 10M, again comparable to the affinity of membrane bound forms of other mammalian interferon- receptors for interferon-. Thus, the myxoma virus M-T7 protein is a functional soluble interferon- receptor homolog which binds and inhibits interferon- with high affinity in a species-specific manner.

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