Ricciardi R P, Jones R L, Cepko C L, Sharp P A, Roberts B E
Proc Natl Acad Sci U S A. 1981 Oct;78(10):6121-5. doi: 10.1073/pnas.78.10.6121.
Host-range mutants of adenovirus 5 that contain a defect in region E1A (0-4.5 units) fail to replicate in HeLa cells and to transform rodent cells. In HeLa cells, these mutants synthesize only the two RNAs from E1A that share the same 5' and 3' termini but differ in length by the amount of internal sequence removed by splicing. RNA from wild-type virus, selected by hybridization to DNA from region E1A, translates into polypeptides of Mr 51,000 and 48,000 that are highly acidic in isoelectric focusing gels. These acidic Mr 51,000 and Mr 48,000 polypeptides are encoded by the longer and shorter E1A RNAs, respectively. Two of the host-range mutants, H5hr1 and H5hr2, fail to synthesize the Mr 51,000 polypeptide but do produce the Mr 48,000 polypeptide and a novel polypeptide thought to be a truncated portion of the Mr 51,000 polypeptide. H5hr1 and H5hr2 are hypothesized to have termination codons in sequences found only in RNA encoding the Mr 51,000 polypeptide. This prediction is verified for H5hr1 by DNA sequence analysis. The other three host-range mutants (H5hr3-5) synthesize both acidic polypeptides and are predicted to be missense. These results strongly imply that the Mr 51,000 polypeptide, alone or in combination with the Mr 48,000 polypeptide, is needed to regulate expression of adjacent viral genes during the early phase of adenovirus infection.
腺病毒5型的宿主范围突变体在E1A区域（0 - 4.5单位）存在缺陷，无法在HeLa细胞中复制，也不能转化啮齿动物细胞。在HeLa细胞中，这些突变体仅合成来自E1A的两种RNA，它们具有相同的5'和3'末端，但长度因剪接去除的内部序列量而不同。通过与E1A区域的DNA杂交筛选出的野生型病毒RNA，可翻译出分子量为51,000和48,000的多肽，在等电聚焦凝胶中呈高酸性。这些酸性的分子量为51,000和48,000的多肽分别由较长和较短的E1A RNA编码。两个宿主范围突变体H5hr1和H5hr2无法合成分子量为51,000的多肽，但能产生分子量为48,000的多肽以及一种被认为是分子量为51,000多肽截短部分的新多肽。据推测，H5hr1和H5hr2在仅存在于编码分子量为51,000多肽的RNA序列中有终止密码子。通过DNA序列分析证实了H5hr1的这一预测。其他三个宿主范围突变体（H5hr3 - 5）能合成两种酸性多肽，预计为错义突变。这些结果强烈表明，在腺病毒感染的早期阶段，分子量为51,000的多肽单独或与分子量为48,000的多肽共同作用，是调节相邻病毒基因表达所必需的。
