Wong P K, Saha K, Lin Y C, Lynn W S, Yuen P H
University of Texas, M. D. Anderson Cancer Center, Science Park-Research Division, Smithville 78957, USA.
Virology. 1996 Jan 15;215(2):203-6. doi: 10.1006/viro.1996.0024.
ts1, a mutant of MoMuLV, selectively kills T cells and neurons in the infected host resulting in neuroimmunodegeneration. In the infected thymus there is an early increase in mitosis of thymocytes followed by rapid death, suggesting that thymocyte death may be induced by viral mitogenic activation. Studies on thymocytes obtained from ts1-infected mice indicated that the ts1-induced depletion of thymocytes is mediated through activation-induced death by apoptosis. To further investigate the interaction between ts1 and thymocytes, we have established long-term primary murine thymocyte cultures by placing the thymocytes together with thymic remnants in culture medium containing IL-2 and IL-7. These thymocytes retained their immature phenotype and we susceptible to infection by ts1 and its parental wild-type MoMuLV. ts1-infected thymocytes proliferated initially at accelerated rate but subsequently produced more infectious virus and died much faster than control or MoMuLV-infected thymocytes. These in vitro studies to some extent reflect our in vivo studies reported previously.
ts1是莫洛尼鼠白血病病毒(MoMuLV)的一种突变体,它能选择性地杀死受感染宿主中的T细胞和神经元,导致神经免疫退化。在受感染的胸腺中,胸腺细胞的有丝分裂早期增加,随后迅速死亡,这表明胸腺细胞死亡可能是由病毒促有丝分裂激活诱导的。对从ts1感染小鼠获得的胸腺细胞的研究表明,ts1诱导的胸腺细胞耗竭是通过凋亡介导的激活诱导死亡实现的。为了进一步研究ts1与胸腺细胞之间的相互作用,我们通过将胸腺细胞与胸腺残余物一起置于含有白细胞介素-2(IL-2)和白细胞介素-7(IL-7)的培养基中,建立了长期的原代小鼠胸腺细胞培养物。这些胸腺细胞保留了它们的未成熟表型,并且易受ts1及其亲本野生型MoMuLV的感染。ts1感染的胸腺细胞最初以加速速率增殖,但随后产生更多的传染性病毒,并且比对照或MoMuLV感染的胸腺细胞死亡得更快。这些体外研究在一定程度上反映了我们之前报道的体内研究结果。