Feldman L T, Imperiale M J, Nevins J R
Proc Natl Acad Sci U S A. 1982 Aug;79(16):4952-6. doi: 10.1073/pnas.79.16.4952.
Adenovirus mutants carrying a defective E1A gene, such as dl312, are unable to express any of the early viral genes upon infection of HeLa cells. However, efficient expression of the other early adenovirus genes was obtained when dl312-infected HeLa cells were coinfected with pseudorabies virus, a herpesvirus. By employing a temperature-sensitive pseudorabies mutant (tsG1) it was demonstrated that the herpesvirus function responsible for the induction of adenovirus transcription was the immediate early gene, a gene required for the activation of herpesvirus early gene expression and the maintenance of early and late herpesvirus transcription. Specifically, HeLa cells coinfected with dl312 and tsG1, when shifted to the nonpermissive temperature, lost their capacity to express the early adenovirus genes. Furthermore, activation of early adenovirus gene expression in herpesvirus coinfection occurred earlier and at a higher level than in wild-type adenovirus infection. Therefore, the herpesvirus immediate early protein not only activates the early adenovirus transcription units but apparently does so more efficiently than the adenovirus E1A gene product. Because of this fact, we argue that the activation, either by the E1A protein or the herpesvirus immediately early protein, most likely occurs indirectly through interaction with a cellular protein rather than by a direct recognition of regulatory sequences at the adenovirus promoters.
携带缺陷型E1A基因的腺病毒突变体，如dl312，在感染HeLa细胞后无法表达任何早期病毒基因。然而，当用伪狂犬病病毒（一种疱疹病毒）与感染了dl312的HeLa细胞共感染时，可实现腺病毒其他早期基因的高效表达。通过使用温度敏感型伪狂犬病突变体（tsG1），证明负责诱导腺病毒转录的疱疹病毒功能是立即早期基因，该基因是激活疱疹病毒早期基因表达以及维持疱疹病毒早期和晚期转录所必需的。具体而言，共感染了dl312和tsG1的HeLa细胞，当转移到非允许温度时，失去了表达腺病毒早期基因的能力。此外，疱疹病毒共感染时腺病毒早期基因表达的激活比野生型腺病毒感染发生得更早且水平更高。因此，疱疹病毒立即早期蛋白不仅能激活腺病毒早期转录单元，而且显然比腺病毒E1A基因产物更有效地做到这一点。基于这一事实，我们认为，无论是由E1A蛋白还是疱疹病毒立即早期蛋白激活，最有可能是通过与一种细胞蛋白相互作用间接发生的，而不是通过直接识别腺病毒启动子处的调控序列。
