Dutheil Nathalie, Yoon-Robarts Miran, Ward Peter, Henckaerts Els, Skrabanek Lucy, Berns Kenneth I, Campagne Fabien, Linden R Michael
Carl C. Icahn Institute for Gene Therapy and Molecular Medicine, Mount Sinai School of Medicine, One Gustave L. Levy Pl., Box 1496, New York, NY 10029, USA.
J Virol. 2004 Aug;78(16):8917-21. doi: 10.1128/JVI.78.16.8917-8921.2004.
The nonpathogenic human adeno-associated virus (AAV) has developed a mechanism to integrate its genome into human chromosome 19 at 19q13.4 (termed AAVS1), thereby establishing latency. Here, we provide evidence that the chromosomal signals required for site-specific integration are conserved in the mouse genome proximal to the recently identified Mbs85 gene. These sequence motifs can be specifically nicked by the viral Rep protein required for the initiation of site-specific AAV DNA integration. Furthermore, these signals can serve as a minimal origin for Rep-dependent DNA replication. In addition, we isolated the mouse Mbs85 proximal promoter and show transcriptional activity in three mouse cell lines.
非致病性人类腺相关病毒(AAV)已形成一种机制,可将其基因组整合到人类19号染色体19q13.4处(称为AAVS1),从而建立潜伏状态。在此,我们提供证据表明,位点特异性整合所需的染色体信号在最近鉴定的Mbs85基因附近的小鼠基因组中是保守的。这些序列基序可被位点特异性AAV DNA整合起始所需的病毒Rep蛋白特异性切割。此外,这些信号可作为Rep依赖性DNA复制的最小起始点。另外,我们分离出了小鼠Mbs85近端启动子,并在三种小鼠细胞系中显示出转录活性。