Huebner K, Tsuchida N, Green C, Croce C M
J Exp Med. 1979 Aug 1;150(2):392-405. doi: 10.1084/jem.150.2.392.
Murine teratocarcinoma stem cells are nonpermissive for productive infection by a variety of DNA (polyoma and SV40 virus) and RNA (murine leukemia and sarcoma virus) tumor viruses whereas differentiated murine cells derived from the stem cells are permissive for productive (or abortive in the case of SV40) infection by these same viruses. The block to productive infection by these oncogenic viruses is at a postpenetration step in the replication cycle of these viruses but the precise level of the block has not been established for any of these viruses. In this report we describe teratocarcinoma-derived stem and differentiated cell lines which should be especially useful in determining the level of the block to replication of ecotropic murine leukemia virus in murine teratocarcinoma stem cells. The stem cell line, OTT6050AF1 BrdU, which is completely nonpermissive to productive infection by Moloney murine leukemia virus and consists of 97% pluripotent stem cells, contains DNA copies of an RNA tumor virus which is indistinguishable from the N-tropic murine leukemia virus of AKR mice. The stem cells are negative for expression of viral reverse transcriptase, p30 and gp69/71 and no virus is found by XC plaque assay or other biological tests. Differentiated cells established from the same teratocarcinoma tumor are 100% positive for viral gp69/71, p30, and produce large amounts of reverse transcriptase activity and N-tropic virus as detected by biological assay. The virus isolated from the differentiated cells is closely related, if not identical to AKR N-tropic virus by nucleic acid hybridization studies and is thus not an endogenous virus of the 129 strain of mice. The teratocarcinoma tumor from which the cell lines were established had been carried in 129 mice and perhaps at some time in the mouse passage history the tumors were infected (nonproductively) with the N-tropic virus. Regardless of the origin of this viral DNA, the OTT6050A derived stem and differentiated cell lines should be extremely useful in defining in stem cells the step at which ecotropic murine leukemia virus replication is blocked.
小鼠畸胎瘤干细胞对多种DNA肿瘤病毒（多瘤病毒和SV40病毒）和RNA肿瘤病毒（小鼠白血病病毒和肉瘤病毒）的增殖性感染具有抗性，而源自这些干细胞的分化小鼠细胞对这些相同病毒的增殖性（或在SV40病毒的情况下为流产性）感染具有敏感性。这些致癌病毒对增殖性感染的阻断发生在病毒复制周期的穿透后步骤，但尚未确定这些病毒中任何一种的确切阻断水平。在本报告中，我们描述了源自畸胎瘤的干细胞系和分化细胞系，它们在确定嗜亲性小鼠白血病病毒在小鼠畸胎瘤干细胞中的复制阻断水平方面应特别有用。干细胞系OTT6050AF1 BrdU对莫洛尼小鼠白血病病毒的增殖性感染完全具有抗性，由97%的多能干细胞组成，含有一种RNA肿瘤病毒的DNA拷贝，该病毒与AKR小鼠的N嗜性小鼠白血病病毒无法区分。干细胞的病毒逆转录酶、p30和gp69/71表达呈阴性，通过XC空斑试验或其他生物学检测未发现病毒。从同一畸胎瘤肿瘤建立的分化细胞对病毒gp69/71、p30呈100%阳性，并产生大量逆转录酶活性和通过生物学检测检测到的N嗜性病毒。通过核酸杂交研究，从分化细胞中分离出的病毒与AKR N嗜性病毒密切相关（如果不是完全相同的话），因此不是129品系小鼠的内源性病毒。建立细胞系所用的畸胎瘤肿瘤是在129小鼠中传代的，也许在小鼠传代历史的某个时候，肿瘤被N嗜性病毒（非增殖性）感染。无论这种病毒DNA的来源如何，源自OTT6050A的干细胞系和分化细胞系在确定嗜亲性小鼠白血病病毒在干细胞中复制被阻断的步骤方面应该非常有用。
