The myxoma virus TNF-receptor homologue (T2) inhibits tumor necrosis factor-α in a species-specific fashion

Martha Schreiber, Grant McFadden

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59 Scopus citations


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 TNFα were expressed independently from vaccinia virus vectors. Growth of the TNFα-expressing viruses was significantly attenuated in TNF-hypersensitive L929-8 cells, and these cells were rapidly lysed by all three TNFαs. Rabbit cells showed strict species specificity in that RK-13 and SIRC cells were only sensitive to lysis by the homologous rabbit TNFα. Although RK-13 cells were hypersensitive to rabbit TNFα 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 TNFα, suggesting that poxviruses possess additional anti-TNF mechanisms. When the ability of the myxoma T2 protein to inhibit biological activities of TNFα was assayed, T2 protein effectively protected L929-8 cells from lysis by rabbit, but not human or mouse TNFα. These studies show that rabbit TNF receptors may be species-specific for rabbit TNFα and we conclude that the myxoma T2 protein evolved to specifically inhibit TNF activities from its natural host, the South American rabbit.

Original languageEnglish (US)
Article number71585
Pages (from-to)692-705
Number of pages14
Issue number2
StatePublished - Nov 1 1994
Externally publishedYes

ASJC Scopus subject areas

  • Virology


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