Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, 450 Brookline Avenue, CLS-1010, Boston, MA, 02215, USA.
Department of Medicine, Harvard Medical School, A-111, 25 Shattuck Street, Boston, MA, 02115, USA.
Cell Mol Life Sci. 2018 Jul;75(14):2491-2507. doi: 10.1007/s00018-018-2772-5. Epub 2018 Feb 7.
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.
整合是 HIV-1 复制的核心，有助于塑造在 AIDS 患者中持续存在的细胞库。HIV-1 与特定的细胞因子相互作用，将整合靶向到染色质中基因密集区转录活跃基因的内部区域。病毒衣壳与几种额外涉及病毒核输入的蛋白质相互作用，包括切割和多聚腺苷酸化特异性因子 6，以抑制整合到异染色质中。病毒整合酶蛋白与转录共激活因子晶状体上皮衍生生长因子 p75 相互作用，主要将整合定位在基因体内。整合酶还感知靶 DNA 扭曲和核苷酸序列，以帮助微调整合位点切割的特定磷酸二酯键。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。
