C/EBP activators are required for HIV-1 replication and proviral induction in monocytic cell lines

C/EBP activators are required for HIV-1 replication and proviral induction in monocytic cell lines
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DOI:
10.1016/s1074-7613(00)80313-1
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发表时间:
1996-07-01
期刊:
影响因子:
32.4
通讯作者:
Calame, KL
Calame, KL
中科院分区:
医学1区
文献类型:
--
作者:
Henderson, AJ;Connor, RI;Calame, KL

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先前的工作表明,C/EBP位点和C/EBP转录激活因子对于单核细胞/巨噬细胞中的HIV-1 LTR活性是必需的。我们研究了C/EBP蛋白在HIV-1诱导和复制中的作用。显性阴性C/EBP蛋白LIP的异位表达抑制HIV-1 mRNA和病毒在活化的U1细胞中的产生,表明C/EBP蛋白是前病毒诱导所必需的。过表达C/EBP激活因子NF-IL-6的U1系在细胞活化后比对照系产生更多的病毒mRNA和病毒颗粒,表明C/EBP蛋白限制病毒转录。在两个C/EBP位点内携带突变的HIV-1在U937前单核细胞中复制的能力被削弱,表明这些位点是复制所必需的。这些数据鉴定了C/EBP蛋白作为单核细胞/巨噬细胞中HIV-1表达的调节剂。
Previous work has shown that C/EBP sites and C/EBP transcriptional activators are necessary for HIV-1 LTR activity in monocytes/macrophages. We have investigated the role that C/EBP proteins play in induction and replication of HIV-1. Ectopic expression of the dominant negative C/EBP protein LIP inhibited HIV-1 mRNA and virus production in activated U1 cells, demonstrating that C/EBP proteins are required for provirus induction. U1 lines overexpressing C/EBP activator NF-IL-6 produced more viral mRNA and virus particles following cellular activation than control lines, demonstrating that C/EBP proteins are limiting for virus transcription. HIV-1 harboring mutations within two C/EBP sites were crippled in their ability to replicate in U937 promonocytic cells, indicating that these sites are required for replication. These data identify C/EBP proteins as regulators of HIV-1 expression in monocytes/macrophages.