Adeno-associated virus site-specifically integrates into a muscle-specific DNA region.
Adeno-associated virus site-specifically integrates into a muscle-specific DNA region.
复制标题
腺相关病毒位点特异性地整合到肌肉特异性 DNA 区域中。
DOI：
10.1073/pnas.080079397
复制
发表时间：
2000
影响因子：
11.1
通讯作者：
Linden,RM
中科院分区：
文献类型：
--
作者：
Dutheil,N;Shi,F;Dupressoir,T;Linden,RM
The nonpathogenic human virus adeno-associated virus type 2 (AAV) has evolved the potentially unique strategy to establish latency by site-specifically integrating its genome into human chromosome 19 (19q13.3-qter) at a locus designatedAAVS1. This nonhomologous, site-specific recombination of viral DNA with the human genome provides a basis for developing targeted gene therapy vectors. To assess whether the region surroundingAAVS1might have contributed to the selection of the specific integration site, we have investigated this locus. Here, we show thatAAVS1is closely linked to the slow skeletal troponin T gene,TNNT1, which has been mapped previously to 19q13.4. In support of this idea, we demonstrate that site-specific AAV DNA integration can result in the formation ofTNNT1-AAV junctions. The question now arises whether muscle represents a natural target tissue for latent AAV infection. This possibility is of additional interest in view of recent observations that muscle tissue is particularly well suited for AAV-mediated gene transfer. The question also occurs whether latent infection by AAV can lead to phenotypic changes of the multinucleated muscle fiber cells.
