VIRUS-INFECTION OF MURINE TERATOCARCINOMA STEM-CELL LINES

VIRUS-INFECTION OF MURINE TERATOCARCINOMA STEM-CELL LINES
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DOI:
10.1016/0092-8674(77)90162-3
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发表时间:
1977-01-01
期刊:
影响因子:
64.5
通讯作者:
LOWY, DR
LOWY, DR
中科院分区:
生物学1区
文献类型:
--
作者:
TEICH, NM;WEISS, RA;LOWY, DR

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研究了三种克隆小鼠畸胎瘤干细胞系对各种不同病毒感染的易感性。当处于未分化状态时,这些胚胎癌干细胞对脑心肌炎病毒、辛德比斯病毒、牛痘病毒和水泡性口炎病毒的感染与来自相同小鼠品系的胚胎成纤维细胞一样敏感。与成纤维细胞不同,未分化的畸胎瘤细胞完全难以感染鼠白血病病毒。如果允许干细胞分化以形成多种分化的细胞类型,则它们变得允许小鼠白血病病毒以低水平复制。采用多种技术探讨了该药物对小鼠白血病病毒感染的阻断作用。在体内或体外不分化的1个无活性细胞系中,病毒吸附和渗透不受限制(通过感染水泡性口炎病毒的鼠白血病病毒假型进行测量),但不能检测到整合的前病毒DNA拷贝。在多能干细胞系中,检测到前病毒DNA序列,但既没有观察到转录成病毒特异性RNA,也没有观察到病毒特异性蛋白质合成。小鼠白血病病毒在细胞中复制的控制显然是分化阶段的功能,也可能是畸胎瘤干细胞的遗传组成的功能。
Three clonal murine teratocarcinoma stem cell lines were studied for susceptibility to infection by a variety of different viruses. When in the undifferentiated state, these embryonal carcinoma stem cells are as sensitive to infection by encephalomyocarditis, Sindbis, vaccinia and vesicular stomatitis viruses as are embryo fibroblasts derived from the same mouse strain. The undifferentiated teratocarcinoma cells, unlike the fibroblasts, are entirely refractory to infection with murine leukemia virus. If the stem cells are allowed to differentiate to form a variety of differentiated cell types, they become permissive for murine leukemia virus replication at a low level. Several techniques were used to elucidate the block to murine leukemia virus infection. In the 1 nullipotent cell line which does not differentiate in vivo or in vitro, virus adsorption and penetration are not restricted (as measured by infection with murine leukemia virus pseudotypes of vesicular stomatitis virus), but an integrated proviral DNA copy cannot be detected. In a pluripotent stem cell line, proviral DNA sequences are detected, but neither transcription into viral specific RNA nor viral specific protein synthesis is observed. The control of murine leukemia virus replication in the cells is apparently a function of the stage of differentiation and perhaps also of the genetic composition of the teratocarcinoma stem cells.