Pentoxifylline suppresses transduction by HIV-1-based vectors.
Pentoxifylline suppresses transduction by HIV-1-based vectors.
复制标题
己酮可可碱抑制基于 HIV-1 的载体的转导。
DOI：
10.1159/000109752
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发表时间：
2007
期刊：
影响因子：
4.6
通讯作者：
Daniel,Rene
中科院分区：
文献类型：
--
作者：
Smith,JohannaA;Nunnari,Giuseppe;Preuss,Mirjam;Pomerantz,RogerJ;Daniel,Rene
喷替福林，一种与咖啡因有关的化合物，被证明可以抑制人类免疫缺陷病毒1型（HIV-1）的复制。这种效应被认为是通过抑制肿瘤坏死因子-α（TNFα）介导的长末端重复序列（LTR）驱动的表达来介导的。我们现在证明，喷替福林有效地抑制转导的HIV-1为基础的载体。后一种效应与LTR驱动的表达无关，并且与感染细胞中整合过程完成效率降低相关。最后，在表达显性负性ATR蛋白的细胞中，以及在表现出低水平ATR活性的原代人细胞中，喷替福林的作用显著降低，这表明喷替福林对HIV-1转导和复制的作用至少部分是由ATR激酶的抑制介导的。
Pentoxifylline, a caffeine-related compound, was shown to suppress human immunodeficiency virus type 1 (HIV-1) replication. This effect is thought to be mediated by inhibition of tumor necrosis factor-alpha (TNFα)-mediated long-terminal repeat (LTR)-driven expression. We now demonstrate that pentoxifylline efficiently inhibits transduction by HIV-1-based vectors. This latter effect is independent of LTR-driven expression, and correlates with a reduced efficiency of the completion of the integration process in infected cells. Finally, the effect of pentoxifylline is dramatically reduced in cells expressing a dominant negative ATR protein, and in primary human cells that exhibit low level of ATR activity, suggesting that the effect of pentoxifylline on HIV-1 transduction and replication is at least partly mediated by suppression of the ATR kinase.