一种指导环状腺相关病毒复制和包装的顺式作用元件。
A cis-acting element that directs circular adeno-associated virus replication and packaging.
作者信息
Musatov Sergei, Roberts Jill, Pfaff Donald, Kaplitt Michael
机构信息
Laboratory of Neurobiology and Behavior, The Rockefeller University, Weill Medical College of Cornell University, 525 East 68th Street, New York, NY 10021, USA.
出版信息
J Virol. 2002 Dec;76(24):12792-802. doi: 10.1128/jvi.76.24.12792-12802.2002.
Abstract
A novel pathway of adeno-associated virus (AAV) replication marked by the assembly of circular monomer duplex intermediates (cAAV) has been recently discovered. In the present report we identify a single AD domain of the inverted terminal repeat as a minimal origin of cAAV replication. A small internal palindrome (BB'), necessary for optimal Rep-inverted terminal repeat interaction, does not contribute to the efficiency of cAAV replication, while the terminal resolution site is an essential cis-acting element. Furthermore, recombinant cAAV vectors that encompass only the AD domain replicate exclusively in a circular form and no detectable linear duplex replicative intermediates are generated, suggesting that both pathways of AAV replication are independent and can be separated. In addition, we show that cAAVs are efficient templates for encapsidation of single-stranded DNA genomes, an observation that assigns a biological role for these novel replication species. Together, these findings shed new light on the current model of AAV replication and packaging.
摘要
最近发现了一种以环状单体双链中间体（cAAV）组装为标志的腺相关病毒（AAV）复制新途径。在本报告中，我们确定了反向末端重复序列的单个AD结构域是cAAV复制的最小起始位点。一个小的内部回文序列（BB'）对于Rep-反向末端重复序列的最佳相互作用是必需的，但对cAAV复制效率没有贡献，而末端切割位点是一个必需的顺式作用元件。此外，仅包含AD结构域的重组cAAV载体仅以环状形式复制，未产生可检测到的线性双链复制中间体，这表明AAV的两种复制途径是独立的且可以分离。此外，我们表明cAAV是单链DNA基因组包装的有效模板，这一观察结果赋予了这些新型复制产物生物学作用。总之，这些发现为当前的AAV复制和包装模型提供了新的线索。
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