GENE-TRANSFER BY RETROVIRUS VECTORS OCCURS ONLY IN CELLS THAT ARE ACTIVELY REPLICATING AT THE TIME OF INFECTION
GENE-TRANSFER BY RETROVIRUS VECTORS OCCURS ONLY IN CELLS THAT ARE ACTIVELY REPLICATING AT THE TIME OF INFECTION
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DOI：
10.1128/mcb.10.8.4239
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发表时间：
1990-08-01
影响因子：
5.3
通讯作者：
MILLER, AD
中科院分区：
文献类型：
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作者：
MILLER, DG;ADAM, MA;MILLER, AD
先前的报道表明，逆转录病毒感染在非复制（静止期[以下称为静止期]）细胞中受到抑制。当细胞在感染后长达一周的时间内被允许复制时，显示发生静止细胞的感染，这表明未整合的逆转录病毒可以在释放复制阻断后以能够整合的形式持续存在。然而，这些研究因使用可复制的病毒而变得复杂，这种病毒可以在受感染的细胞中传播。我们已经使用了复制缺陷型逆转录病毒载体，以比较稳定和复制大鼠胚胎成纤维细胞的基因转移效率。与之前的结果一致，基因转移在静止细胞与复制细胞中被抑制100倍。与先前报道的结果相反，感染的阻断不能通过刺激静止细胞在感染后6小时至10天分裂来缓解。因此，对于成功的逆转录病毒感染，感染的细胞必须在感染时复制。这些结果对逆转录病毒载体用于基因转移具有重要意义。
Previous reports have shown that retrovirus infection is inhibited in nonreplicating (stationary-phase [hereafter called stationary]) cells. Infection of stationary cells was shown to occur when the cells were allowed to replicate at times up to a week after infection, suggesting that an unintegrated retrovirus could persist in a form that was competent to integrate after release of the block to replication. However, those studies were complicated by the use of replication-competent virus, which can spread in the infected cells. We have used a replication-defective retrovirus vector to compare the efficiency of gene transfer in stationary and replicating rat embryo fibroblasts. In agreement with previous results, gene transfer was inhibited 100-fold in stationary versus replicating cells. In contrast to previously reported results, the block to infection could not be relieved by stimulating stationary cells to divide at times from 6 h to 10 days after infection. Thus, for successful retroviral infection, the infected cells must be replicating at the time of infection. These results have important implications for the use of retroviral vectors for gene transfer.