The myxoma virus-soluble interferon-gamma receptor homolog, M-T7, inhibits interferon-gamma in a species-specific manner.
The myxoma virus M-T7 protein contains significant sequence similarity to the ligand binding domain of the mammalian interferon-gamma receptors, and functions as a soluble homolog which can bind and inhibit the biological activities of rabbit interferon-gamma (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 x 10(7) 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-gamma, and did not bind either human or murine interferon-gamma. Scatchard analysis of rabbit interferon-gamma binding curves yielded a single high affinity binding site on M-T7, with a Kd of 1.2 x 10(-9) M, which is comparable to the affinity between soluble forms of cellular interferon-gamma receptors and their cognate ligands. In comparison, rabbit interferon-gamma was shown to bind its cellular receptor with a Kd of 5.9 x 10(-10) M, again comparable to the affinity of membrane bound forms of other mammalian interferon-gamma receptors for interferon-gamma. Thus, the myxoma virus M-T7 protein is a functional soluble interferon-gamma receptor homolog which binds and inhibits interferon-gamma with high affinity in a species-specific manner.
Department of Biochemistry, University of Alberta, Edmonton, Canada.
K
K
Mossman
C
C
Upton
G
G
McFadden
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D017931:DNA Primers; D005814:Genes, Viral; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007700:Kinetics; D008322:Mammals; D008969:Molecular Sequence Data; D009233:Myxoma virus / Q000276:immunology / Q000378:metabolism*; D011817:Rabbits; D017471:Receptors, Interferon / Q000096:biosynthesis / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism / Q000494:pharmacology; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000096:biosynthesis / Q000378:metabolism / Q000494:pharmacology*; D000096743:Interferon gamma Receptor
D017931:DNA Primers; D007371:Interferon-gamma; D017471:Receptors, Interferon; D011994:Recombinant Proteins; D014764:Viral Proteins; D000096743:Interferon gamma Receptor; C091989:M-T7 protein, Myxoma virus