Inhibition of HIV-1 replication by RNA interference of p53 expression
Inhibition of HIV-1 replication by RNA interference of p53 expression
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DOI：
10.1189/jlb.0306189
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发表时间：
2006-09-01
影响因子：
5.5
通讯作者：
Este, Jose A.
中科院分区：
文献类型：
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作者：
Pauls, Eduardo;Senserrich, Jordi;Este, Jose A.
P53的表达和激活与人类免疫缺陷病毒(HIV)疾病进展速度加快有关，最有可能的是通过诱导CD4+T细胞死亡，但也通过其在病毒调节蛋白控制病毒基因转录方面的协同作用。在这里，我们显示了在HIV-1报告细胞(HeLa P4-R5 MAGI)和淋巴样细胞(SupT1)中P53的RNA干扰阻止了HIV-1和TAT诱导的HIV-1启动子的转录和急性感染细胞中的HIV-1复制，表明P53在HIV-1转录中起协同作用。与在P53 DNA结合域上编码几个突变的SupT1细胞相反，在HeLa P4-R5 MAGI与持续感染的HIV-1细胞共培养中，HIV-1诱导的合胞体的死亡减少。据我们所知，这是第一次证明了P53在HIV-1复制中功能丧失的影响，这一作用独立于其经典的DNA结合活性。我们的结果表明，P53在HIV-1感染中有两个独立的作用：在HIV长末端重复转录中的协同作用和病毒诱导的细胞死亡。
p53 expression and activation have been associated to faster human immunodeficiency virus (HIV) disease progression, most probably by inducing CD4+ T cell death but also through its cooperative effect in the control of viral gene transcription by viral regulatory proteins. Here, we show that RNA interference of p53 in HIV-1 reporter (HeLa P4-R5 MAGI) and lymphoid (SupT1) cell fines blocked HIV-1 and Tat-induced transcription from the HIV-1 promoter and HIV-1 replication in acutely infected cells, suggesting a cooperative role of p53 in HIV-1 transcription. Contrary to SupT1 cells, which encode several mutations on the p53 DNA binding domain, death of HIV-1-induced syncytia was reduced in cocultures of HeLa P4-R5 MAGI with persistently infected HIV-1 cells. To our knowledge, this is the first demonstration of the effect of the loss of function of p53 in HIV-1 replication, which is independent on its classical DNA binding activity. Our results suggest two independent roles for p53 in HIV-1 infection: cooperation in HIV long-terminal repeat transcription and virus-induced cell death.