Labow M A, Hermonat P L, Berns K I
J Virol. 1986 Oct;60(1):251-8. doi: 10.1128/JVI.60.1.251-258.1986.
The defective human parvovirus, adeno-associated virus (AAV), requires multiple functions provided by a coinfecting helper virus for viral replication. In addition, it has recently been shown that at least one AAV gene is also required for AAV DNA replication. In this paper, we investigate the autoregulation of the AAV genome by analyzing the expression of mutant AAV genomes upon transfection into adenovirus-infected human cells. Evidence is presented which indicates that the AAV genome regulates its own gene expression in at least two ways. First, either the AAV p5 gene or both the p5 and p19 genes appear to encode a trans activator of AAV transcription. Frameshift mutations within the p5 or p19 gene severely inhibited the synthesis and accumulation of all AAV transcripts. The defective accumulation of transcripts could be complemented in trans, in a manner independent of DNA replication, by cotransfection with a capsid deletion mutant. Second, evidence is presented which suggests that the p5 and p19 genes contain negative cis-active regulatory elements. Deletion of sequences within the p5 and p19 genes enhanced the accumulation of the p5 transcript in cis upon complementation with an AAV capsid deletion mutant, whereas certain deletions enhanced p40 RNA accumulation in the absence of trans activation by the p5 gene.
有缺陷的人类细小病毒——腺相关病毒（AAV），需要共感染的辅助病毒提供多种功能才能进行病毒复制。此外，最近研究表明，AAV DNA复制至少还需要一个AAV基因。在本文中，我们通过分析突变型AAV基因组转染到腺病毒感染的人类细胞后的表达情况，来研究AAV基因组的自我调节。有证据表明，AAV基因组至少通过两种方式调节其自身的基因表达。首先，AAV p5基因或p5和p19基因似乎都编码一种AAV转录的反式激活因子。p5或p19基因内的移码突变严重抑制了所有AAV转录本的合成和积累。转录本的缺陷性积累可以通过与衣壳缺失突变体共转染，以一种独立于DNA复制的方式进行反式互补。其次，有证据表明p5和p19基因含有负性顺式作用调节元件。p5和p19基因内序列的缺失在与AAV衣壳缺失突变体互补时，会顺式增强p5转录本的积累，而某些缺失在没有p5基因反式激活的情况下会增强p40 RNA的积累。
