Zhang S, Mak S, Branton P E
Department of Biology, McMaster University, Hamilton, Ontario, Canada.
Virology. 1992 Dec;191(2):793-802. doi: 10.1016/0042-6822(92)90255-n.
Early region 1B (E1B) of human adenoviruses encodes two major proteins. The 19-kDa polypeptide appears to prevent E1A-induced cytolysis and DNA degradation. The larger E1B product of approximately 55 kDa, which is essential for viral replication, plays a role in the accumulation and stability of viral mRNAs and the late shutoff of host metabolism. For serotype 12 (Ad12), this 482-residue (482R) protein is essential for viral DNA replication. In the present report we have used a series of mutants to examine the roles of Ad12 482R and the 19-kDa, 163R protein in the metabolism of early viral mRNAs. No specific effects on the accumulation of early (or late) mRNAs were detected with any of the mutants affecting 163R. With mutant dl42, which encodes an altered 482R product that lacks residues 114-155, both viral DNA replication and late viral protein synthesis were defective. Accumulation of E1A transcripts in the nucleus and cytoplasm resembled wt. The levels of mRNAs from early regions E1B, E2A and E3 at later times during infection were somewhat lower than those of wt, but this decrease may have been due to the absence of progeny viral DNA in dl42-infected cells. However, the accumulation of both E2B and E4 mRNAs at all times was severely reduced. These data suggested that the requirement of 482R for Ad12 DNA replication may be related to its specific role in the metabolism of E2B and E4 mRNAs that encode products necessary for viral DNA synthesis.
人类腺病毒的早期区域1B（E1B）编码两种主要蛋白质。19 kDa的多肽似乎可防止E1A诱导的细胞溶解和DNA降解。约55 kDa的较大E1B产物对病毒复制至关重要，它在病毒mRNA的积累和稳定性以及宿主代谢的晚期关闭中发挥作用。对于12型血清型（Ad12），这种482个氨基酸残基（482R）的蛋白质对病毒DNA复制至关重要。在本报告中，我们使用了一系列突变体来研究Ad12 482R和19 kDa、163R蛋白质在早期病毒mRNA代谢中的作用。影响163R的任何突变体均未检测到对早期（或晚期）mRNA积累的特异性影响。对于编码缺少114 - 155位残基的改变的482R产物的突变体dl42，病毒DNA复制和晚期病毒蛋白合成均存在缺陷。E1A转录本在细胞核和细胞质中的积累与野生型相似。感染后期来自早期区域E1B、E2A和E3的mRNA水平略低于野生型，但这种下降可能是由于dl42感染的细胞中没有子代病毒DNA。然而，E2B和E4 mRNA在所有时间的积累均严重减少。这些数据表明，Ad12 DNA复制对482R的需求可能与其在编码病毒DNA合成所需产物的E2B和E4 mRNA代谢中的特定作用有关。
