Identification of HIV-1 Tat-Associated Proteins Contributing to HIV-1 Transcription and Latency.
Identification of HIV-1 Tat-Associated Proteins Contributing to HIV-1 Transcription and Latency.
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DOI：
10.3390/v9040067
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发表时间：
2017-04-01
期刊：
影响因子：
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通讯作者：
Zhu J
中科院分区：
文献类型：
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作者：
Jean MJ;Power D;Kong W;Huang H;Santoso N;Zhu J
人类免疫缺陷病毒1型（HIV-1）达特是一种病毒编码的反式激活因子，在病毒转录中起核心作用。我们使用我们最近开发的体外翻译开放阅读框架（ORF）（PLATO）方法的平行分析来鉴定与HIV-1达特相关的宿主蛋白。从这个蛋白质组学分析，我们确定了89 Tat相关蛋白（TAP）。我们将我们的结果与达特或长末端重复序列（LTR）相关蛋白的其他数据集相结合。对于其中的一些蛋白质（NAT 10、TINP 1、XRCC 5、SIN 3A），我们证实它们与达特有很强的关联。这些TAP还抑制Tat介导的HIV-1转录。消除对HIV-1转录的抑制有利于逆转整合后潜伏的HIV-1前病毒。我们证明，这些转录抑制TAP有助于HIV-1的潜伏期在Jurkat潜伏期（J-LAT）细胞。因此，我们的蛋白质组学分析突出了以前未被重视的TAP，这些TAP在维持HIV-1潜伏期方面发挥了作用，并且可以作为“休克和杀死”HIV-1治愈策略的潜在药理学靶点进行进一步研究。
Human immunodeficiency virus type 1 (HIV-1) Tat is a virus-encoded trans-activator that plays a central role in viral transcription. We used our recently developed parallel analysis of in vitro translated open reading frames (ORFs) (PLATO) approach to identify host proteins that associate with HIV-1 Tat. From this proteomic assay, we identify 89 Tat-associated proteins (TAPs). We combine our results with other datasets of Tat or long terminal repeat (LTR)-associated proteins. For some of these proteins (NAT10, TINP1, XRCC5, SIN3A), we confirm their strong association with Tat. These TAPs also suppress Tat-mediated HIV-1 transcription. Removing suppression of HIV-1 transcription benefits the reversal of post-integrated, latent HIV-1 proviruses. We demonstrate that these transcriptionally suppressing TAPs contribute to HIV-1 latency in Jurkat latency (J-LAT) cells. Therefore, our proteomic analysis highlights the previously unappreciated TAPs that play a role in maintaining HIV-1 latency and can be further studied as potential pharmacological targets for the “shock and kill” HIV-1 cure strategy.