Macen J L, Graham K A, Lee S F, Schreiber M, Boshkov L K, McFadden G
Department of Biochemistry, University of Alberta, Edmonton, Alberta, T6G 2H7, Canada.
Virology. 1996 Apr 1;218(1):232-7. doi: 10.1006/viro.1996.0183.
Myxoma virus is a leporipoxvirus that causes a highly lethal virulent disease known as myxomatosis in the European rabbit. An important aspect of myxoma virus pathogenesis is the ability of the virus to productively infect lymphocytes and spread to secondary sites via lymphatic channels. We investigated the infection of the CD4+ T lymphoma cell line RL-5 with myxoma virus and Shope fibroma virus, a related but benign leporipoxvirus, and observed that myxoma virus, but not Shope fibroma virus, was able to productively infect RL-5 cells. We also discovered that infection of RL-5 cells with Shope fibroma virus or attenuated myxoma virus mutants containing disruptions in either the T2 or the M11L gene resulted in the rapid induction of DNA fragmentation, followed by morphological changes and loss in cell integrity characteristic of cell death by apoptosis. Purified exogenous T2 protein was unable to prevent apoptosis, suggesting that T2 functions intracellularly. Thus, myxoma virus T2, originally described as a secreted homologue of the tumor necrosis factor receptor, and M11L, a novel transmembrane species with no known cellular homologue, function to extend virus host range for replication in rabbit T lymphocytes through the inhibition of apoptosis in infected T lymphocytes.
黏液瘤病毒是一种兔痘病毒，可在欧洲兔中引发一种名为黏液瘤病的高度致命性烈性疾病。黏液瘤病毒发病机制的一个重要方面是该病毒能够有效感染淋巴细胞，并通过淋巴管道扩散至继发部位。我们研究了黏液瘤病毒和肖普纤维瘤病毒（一种相关的良性兔痘病毒）对CD4 + T淋巴瘤细胞系RL - 5的感染情况，观察到黏液瘤病毒能够有效感染RL - 5细胞，而肖普纤维瘤病毒则不能。我们还发现，用肖普纤维瘤病毒或在T2或M11L基因中含有缺失的减毒黏液瘤病毒突变体感染RL - 5细胞，会导致DNA片段化迅速诱导，随后出现形态变化以及细胞完整性丧失，这是细胞凋亡导致细胞死亡的特征。纯化的外源性T2蛋白无法阻止细胞凋亡，这表明T2在细胞内发挥作用。因此，最初被描述为肿瘤坏死因子受体分泌同源物的黏液瘤病毒T2，以及一种没有已知细胞同源物的新型跨膜蛋白M11L，通过抑制受感染T淋巴细胞中的细胞凋亡，来扩大病毒在兔T淋巴细胞中复制的宿主范围。
