Schreiber M, McFadden G
Department of Biochemistry, University of Alberta, Edmonton, Canada.
Virology. 1994 Nov 1;204(2):692-705. doi: 10.1006/viro.1994.1585.
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.
黏液瘤病毒T2蛋白与肿瘤坏死因子（TNF）受体的配体结合域具有广泛的同源性。为了表征T2与TNF的相互作用，黏液瘤T2蛋白以及兔、小鼠和人TNFα分别由痘苗病毒载体独立表达。表达TNFα的病毒在TNF超敏L929 - 8细胞中的生长显著减弱，并且这三种TNFα均可使这些细胞迅速裂解。兔细胞表现出严格的物种特异性，即RK - 13和SIRC细胞仅对同源兔TNFα的裂解敏感。尽管即使在没有蛋白质合成抑制剂的情况下RK - 13细胞对兔TNFα也超敏，但在兔TNFα存在的情况下，不表达T2的黏液瘤病毒和痘苗病毒在RK - 13细胞中的生长仅略有降低，这表明痘病毒具有额外的抗TNF机制。当检测黏液瘤T2蛋白抑制TNFα生物学活性的能力时，T2蛋白有效地保护L929 - 8细胞免受兔TNFα的裂解，但不能保护其免受人或小鼠TNFα的裂解。这些研究表明兔TNF受体可能对兔TNFα具有物种特异性，并且我们得出结论，黏液瘤T2蛋白进化为特异性抑制其天然宿主南美兔的TNF活性。
