Department of Biological Sciences, University of Warwick, Gibbet Hill Rd., Coventry CV4 7AL, United Kingdom.
J Virol. 2010 Jul;84(14):7096-104. doi: 10.1128/JVI.00107-10. Epub 2010 May 5.
During human adenovirus 5 infection, a temporal cascade of gene expression leads ultimately to the production of large amounts of the proteins needed to construct progeny virions. However, the mechanism for the activation of the major late gene that encodes these viral structural proteins has not been well understood. We show here that two key positive regulators of the major late gene, L4-22K and L4-33K, previously thought to be expressed under the control of the major late promoter itself, initially are expressed from a novel promoter that is embedded within the major late gene and dedicated to their expression. This L4 promoter is required for late gene expression and is activated by a combination of viral protein activators produced during the infection, including E1A, E4 Orf3, and the intermediate-phase protein IVa2, and also by viral genome replication. This new understanding redraws the long-established view of how adenoviral gene expression patterns are controlled and offers new ways to manipulate that gene expression cascade for adenovirus vector applications.
在人类腺病毒 5 感染期间，基因表达的时间级联最终导致产生大量构建子代病毒粒子所需的蛋白质。然而，激活编码这些病毒结构蛋白的主要晚期基因的机制尚未得到很好的理解。我们在这里表明，两个主要晚期基因的关键正调控因子 L4-22K 和 L4-33K，以前被认为是在主要晚期启动子自身的控制下表达的，最初是从一个嵌入主要晚期基因并专门用于其表达的新启动子表达的。这个 L4 启动子是晚期基因表达所必需的，它被在感染过程中产生的病毒蛋白激活剂激活，包括 E1A、E4 Orf3 和中间阶段蛋白 IVa2，也被病毒基因组复制激活。这种新的理解重新描绘了人们长期以来对腺病毒基因表达模式如何受到控制的看法，并为腺病毒载体应用中对该基因表达级联的操纵提供了新的途径。
