Lewis A M, Breeden J H, Wewerka Y L, Schnipper L E, Levine A S
Cold Spring Harb Symp Quant Biol. 1975;39 Pt 1:651-6. doi: 10.1101/sqb.1974.039.01.078.
Adenovirus 2 does not produce tumors when injected into newborn hamsters, and this failure is not corrected by the acquisition of the portion of the SV40 genome present in any of the nondefective Ad2-SV40 hybrid viruses. However, nonhybrid Ad2 will transform hamster cells in vitro, and these transformed cells will produce tumors when injected into newborn hamsters. This finding, taken in conjunction with other studies (Graham et al., this volume; McAllister et al., 1969; McDougall et al., this volume; Williams 1973), suggests that the categorization of Ad2 and Ad5 as "nononcogenic" viruses is a reflection of host response rather than an intrinsic property of the viruses. However, transformation of hamster cells by Ad2 is inefficient, requiring 10(7)-10(8) PFU to produce a focus of transformed cells. Transformation of hamster kidney cells by the nondefective hybrids cannot be associated with portions of the SV40 genome. During the transformation process, complex interactions must occur between the hamster cell genome and the viral genome of Ad2 or the nondefective hybrids. Thus while it appears that there is very little Ad2 DNA in one nonhybrid Ad2-transformed cell line, there is a larger amount of Ad2 DNA in all of the hybrid virus-transformed cell lines. Moreover, while one Ad2+ND2-transformed line has apparently lost the SV40 portion of the viral genome, it is present and transcribed in another line transformed by the same virus. Finally, in the lines of nondefective hybrid-transformed cells examined thus far, there is extensive transcription from the Ad2 H strand. This pattern of transcription differs from transcription of the viral genome in most hybrid Ad2-transformed hamster and rat cells in which L-strand transcripion predominates.
将腺病毒2注射到新生仓鼠体内不会产生肿瘤,而且通过获得任何非缺陷型Ad2 - SV40杂交病毒中存在的SV40基因组部分也无法纠正这种无致瘤性。然而,非杂交的Ad2能在体外转化仓鼠细胞,这些转化细胞注射到新生仓鼠体内会产生肿瘤。这一发现与其他研究(格雷厄姆等人,本卷;麦卡利斯特等人,1969年;麦克杜格尔等人,本卷;威廉姆斯,1973年)相结合,表明将Ad2和Ad5归类为“非致癌”病毒反映的是宿主反应,而非病毒的内在特性。然而,Ad2对仓鼠细胞的转化效率很低,需要10⁷ - 10⁸个空斑形成单位才能产生一个转化细胞集落。非缺陷型杂交病毒对仓鼠肾细胞的转化与SV40基因组的部分无关。在转化过程中,仓鼠细胞基因组与Ad2或非缺陷型杂交病毒的病毒基因组之间必定会发生复杂的相互作用。因此,虽然在一个非杂交Ad2转化的细胞系中似乎只有很少量的Ad2 DNA,但在所有杂交病毒转化的细胞系中都有较多的Ad2 DNA。此外,虽然一个Ad2 + ND2转化的细胞系显然已经丢失了病毒基因组的SV40部分,但在另一个由同一病毒转化的细胞系中它却存在并转录。最后,在迄今为止检测的非缺陷型杂交转化细胞系中,Ad2 H链有广泛的转录。这种转录模式与大多数杂交Ad2转化的仓鼠和大鼠细胞中以L链转录为主的病毒基因组转录不同。