The myxoma virus TNF-receptor homologue (T2) inhibits tumor necrosis factor-alpha in a species-specific fashion.
The myxoma virus T2 protein shares extensive homology with the ligand binding domains of tumor necrosis factor (TNF) receptors. To characterize the T2-TNF interaction, myxoma T2 protein and rabbit, mouse, and human TNF alpha were expressed independently from vaccinia virus vectors. Growth of the TNF alpha-expressing viruses was significantly attenuated in TNF-hypersensitive L929-8 cells, and these cells were rapidly lysed by all three TNF alpha s. Rabbit cells showed strict species specificity in that RK-13 and SIRC cells were only sensitive to lysis by the homologous rabbit TNF alpha. Although RK-13 cells were hypersensitive to rabbit TNF alpha even in the absence of protein synthesis inhibitors, growth of T2 nonexpressing myxoma and vaccinia viruses in RK-13 cells was only modestly reduced in the presence of rabbit TNF alpha, suggesting that poxviruses possess additional anti-TNF mechanisms. When the ability of the myxoma T2 protein to inhibit biological activities of TNF alpha was assayed, T2 protein effectively protected L929-8 cells from lysis by rabbit, but not human or mouse TNF alpha. These studies show that rabbit TNF receptors may be species-specific for rabbit TNF alpha and we conclude that the myxoma T2 protein evolved to specifically inhibit TNF activities from its natural host, the South American rabbit.
Schreiber
M
M
Department of Biochemistry, University of Alberta, Edmonton, Canada.
McFadden
G
G
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009233:Myxoma virus / Q000502:physiology*; D011817:Rabbits; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013045:Species Specificity; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D014616:Vaccinia virus / Q000235:genetics; D014764:Viral Proteins / Q000502:physiology*
D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D014764:Viral Proteins