Y-box-binding protein 1 supports the early and late steps of HIV replication.
Y-box-binding protein 1 supports the early and late steps of HIV replication.
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DOI：
10.1371/journal.pone.0200080
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Debyser Z
中科院分区：
文献类型：
--
作者：
Weydert C;van Heertum B;Dirix L;De Houwer S;De Wit F;Mast J;Husson SJ;Busschots K;König R;Gijsbers R;De Rijck J;Debyser Z
人类免疫缺陷病毒（HIV）依赖于细胞蛋白质，即所谓的辅因子，来完成其复制周期。为了寻找新的治疗靶点，我们鉴定了DNA和RNA结合蛋白Y盒结合蛋白1（YB-1）作为支持HIV复制早期和晚期步骤的辅因子。YB-1耗竭导致HIV-1在不同细胞系中的复制减少10倍。对复制缺陷的分析表明，由于干扰病毒RNA代谢，YB-1的敲低与病毒体产生的2- 5倍减少有关。使用单轮病毒感染实验，我们证明了早期HIV-1复制也取决于细胞YB-1水平。更确切地说，使用定量PCR和荧光标记病毒颗粒的体内核输入测定，我们表明YB-1敲低导致HIV-1逆转录和核输入之间的阻断。相互作用的研究表明，YB-1与整合酶，虽然与HIV整合酶的直接相互作用不能明确证明。总之，我们的研究结果表明YB-1影响HIV复制的多个阶段。未来对YB-1与病毒之间相互作用的研究将揭示这种蛋白质是否有资格成为新的抗病毒靶点。
The human immunodeficiency virus (HIV) depends on cellular proteins, so-called cofactors, to complete its replication cycle. In search for new therapeutic targets we identified the DNA and RNA binding protein Y-box-binding Protein 1 (YB-1) as a cofactor supporting early and late steps of HIV replication. YB-1 depletion resulted in a 10-fold decrease in HIV-1 replication in different cell lines. Dissection of the replication defects revealed that knockdown of YB-1 is associated with a 2- to 5-fold decrease in virion production due to interference with the viral RNA metabolism. Using single-round virus infection experiments we demonstrated that early HIV-1 replication also depends on the cellular YB-1 levels. More precisely, using quantitative PCR and an in vivo nuclear import assay with fluorescently labeled viral particles, we showed that YB-1 knockdown leads to a block between reverse transcription and nuclear import of HIV-1. Interaction studies revealed that YB-1 associates with integrase, although a direct interaction with HIV integrase could not be unambiguously proven. In conclusion, our results indicate that YB-1 affects multiple stages of HIV replication. Future research on the interaction between YB-1 and the virus will reveal whether this protein qualifies as a new antiviral target.
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