Cellular and molecular mechanisms of HIV-1 integration targeting.

Cellular and molecular mechanisms of HIV-1 integration targeting.
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DOI:
10.1007/s00018-018-2772-5
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发表时间:
2018-07
期刊:
Cellular and molecular life sciences : CMLS
影响因子:
--
通讯作者:
Singh PK
Singh PK
中科院分区:
其他
文献类型:
--
作者:
Engelman AN;Singh PK

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整合是HIV-1复制的核心,并有助于塑造持续存在于艾滋病患者体内的细胞储存库。HIV-1与特定的细胞因子相互作用,靶向整合到染色质基因密集区域内转录活性基因的内部区域。病毒衣壳与几种与病毒核输入有关的蛋白相互作用,包括切割和多聚腺苷化特异性因子6,以抑制整合到异染色质。病毒整合酶蛋白与转录共激活因子晶状体上皮源性生长因子p75相互作用,主要定位整合在基因体中。整合酶还可以感知目标DNA扭曲和核苷酸序列,以帮助微调在整合位点断裂的特定磷酸二酯键。针对HIV-1整合靶向的病毒-宿主相互作用的研究有助于开发一类新型的整合酶抑制剂,并可能有助于提高基于病毒的基因治疗载体的安全性。
Integration is central to HIV-1 replication and helps mold the reservoir of cells that persists in AIDS patients. HIV-1 interacts with specific cellular factors to target integration to interior regions of transcriptionally active genes within gene dense regions of chromatin. The viral capsid interacts with several proteins that are additionally implicated in virus nuclear import, including cleavage and polyadenylation specificity factor 6, to suppress integration into heterochromatin. The viral integrase protein interacts with transcriptional co-activator lens epithelium-derived growth factor p75 to principally position integration within gene bodies. The integrase additionally senses target DNA distortion and nucleotide sequence to help fine tune the specific phosphodiester bonds that are cleaved at integration sites. Research into virus-host interactions that underlie HIV-1 integration targeting has aided the development of a novel class of integrase inhibitors and may help to improve the safety of viral-based gene therapy vectors.
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