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首页> 外文期刊>Molecular and Cellular Biology >Regulation of adenovirus gene expression in human WI38 cells by an E1B-encoded tumor antigen.
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Regulation of adenovirus gene expression in human WI38 cells by an E1B-encoded tumor antigen.

机译：E1B编码的肿瘤抗原对人WI38细胞中腺病毒基因表达的调节。

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Adenovirus mutants carrying alterations in the gene encoding the E1B 19-kilodalton tumor antigen (19K protein) cause enhanced cytopathic effect (cyt phenotype) and the degradation of host-cell chromosomal DNA (deg phenotype) upon infection of human HeLa or KB cells. Furthermore, E1B 19K gene mutant viruses are defective for cellular transformation. We report that these mutant viruses possess a host-range phenotype for growth in human cells. In human HeLa cells the mutant viruses grew to the same levels as the wild-type virus, but they were severely defective for growth in KB cells. In human WI38 cells, the E1B 19K gene mutant viruses had a substantial growth advantage over the wild-type virus, yielding 500-fold-higher titers. Viral DNA synthesis was reduced 10- to 20-fold in WI38 cells infected with the wild-type virus relative to that synthesized by the E1B mutant viruses. Viral early and late protein synthesis was similarly reduced in wild type- relative to mutant-infected cells. These reduced levels of early gene expression in wild-type virus-infected cells were paralleled by comparably reduced levels of early cytoplasmic mRNA. The primary cause of this host-range phenotype appeared at the level of early gene transcription, since transcription of viral early genes in the mutant-infected cells was substantially greater than levels found in cells infected with the wild-type virus. These results implicate the E1B 19K tumor antigen in the regulation of adenovirus early gene expression. Specifically, the E1B 19K protein directly or indirectly exerts a negative effect on early gene transcription accounting for efficient gene expression from the E1B mutant viruses in WI38 cells. Based on these findings it is probable that the cyt and deg phenotypes observed in mutant-infected HeLa and KB cells are the result of the pleiotropic effect of this altered gene regulation.
机译：感染人类HeLa或KB细胞后，携带编码E1B 19-千金尔顿肿瘤抗原（19K蛋白）的基因发生改变的腺病毒突变体会引起增强的细胞病变作用（细胞表型）和宿主细胞染色体DNA的降解（度表型）。此外，E1B 19K基因突变病毒不能进行细胞转化。我们报告说，这些突变病毒拥有在人类细胞中生长的宿主范围表型。在人类HeLa细胞中，突变病毒的生长水平与野生型病毒相同，但它们对于KB细胞的生长具有严重缺陷。在人类WI38细胞中，E1B 19K基因突变病毒比野生型病毒具有明显的生长优势，其效价高500倍。相对于由E1B突变病毒合成的WI38细胞，病毒DNA合成在被野生型病毒感染的WI38细胞中降低了10到20倍。相对于突变体感染的细胞，野生型中病毒的早期和晚期蛋白质合成相似地减少。在野生型病毒感染的细胞中，这些早期基因表达水平的降低与早期细胞质mRNA水平的降低相对应。这种宿主范围表型的主要原因是在早期基因转录水平上出现的，因为在突变体感染的细胞中病毒早期基因的转录水平大大高于在野生型病毒感染的细胞中发现的水平。这些结果暗示了E1B 19K肿瘤抗原参与了腺病毒早期基因表达的调控。具体而言，E1B 19K蛋白直接或间接对早期基因转录产生负面影响，这说明了WI38细胞中E1B突变病毒的有效基因表达。基于这些发现，很可能在突变体感染的HeLa和KB细胞中观察到的cyt和deg表型是这种基因调控改变的多效作用的结果。

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