由VAP-A,ORP3和Rab7复合体介导的HIV-1诱导的核侵染解释了激活的T细胞感染的原因
Mark F Santos1, Germana Rappa1, Jana Karbanová2
1Touro University Nevada College of Osteopathic Medicine, Henderson, NV, USA.
Nature communications
|August 10, 2023
概括
人类免疫缺陷病毒1 (HIV-1) 使用Rab7+晚期内和VOR复合体来形成核膜侵入 (NEI) 进入核. 这一途径对于T细胞中HIV-1感染的生产性至关重要.
科学领域:
- 细胞生物学 细胞生物学
- 病毒学 病毒学
- 分子生物学分子生物学
背景情况:
- 核入口对于人类免疫缺陷病毒1 (HIV-1) 生产性感染至关重要.
- 控制HIV-1核进口的精确分子机制仍未完全阐明.
研究的目的:
- 研究涉及HIV-1核入侵的细胞通路和分子参与者.
- 确定潜在的治疗点来抑制HIV-1感染.
主要方法:
- 使用的HeLa细胞和原始激活的CD4+T细胞感染了伪型HIV-1.
- 使用基因沉默 (VAP-A,ORP3) 和药物治疗来破坏VOR复合体和Rab7结合.
- 分析了核包膜侵蚀 (NEI) 和HIV-1核转移的形成.
主要成果:
- 含有HIV-1的Rab7+晚期内分泌体通过VOR复合体 (VAP-A,ORP3,Rab7) 促进NEI的形成.
- 破坏VOR复合体或Rab7结合抑制HIV-1核转移和生产性感染.
- 在耐性静止CD4+T细胞中,ORP3没有过酸化,VOR复合体/NEI形成不存在.
结论:
- 一个涉及VOR复合体和NEI的新型细胞通路促进HIV-1进入核.
- 这条通路在允许细胞中活跃,但在耐性静止T细胞中不存在.
- VOR复合物及其相关分子代表了HIV-1和其他可能需要进入核的病毒的潜在治疗点.
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