在自发控制HIV-1的个体中明显的病毒储存
Chenyang Jiang1,2, Xiaodong Lian1,2, Ce Gao1
1Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
Nature
|August 28, 2020
概括
精英控制者在没有药物的情况下自然控制HIV-1, 通过在特定的静止基因组位置保存完整的病毒DNA. 这种独特的前病毒储存结构可能是有效治愈HIV-1的关键.
科学领域:
- 病毒学
- 免疫学
- 遗传学
背景情况:
- 持续的,无药物控制的HIV-1 (人类免疫缺陷病毒1型) 是罕见的,发生在<0.5%的感染个体中,被称为精英控制者.
- 了解精英控制者的病毒储存的特征对于开发功能性HIV-1治疗至关重要.
研究的目的:
- 在精英控制器中描述病毒储存库及其集成点.
- 确定自然HIV-1控制的潜在结构相关性.
主要方法:
- 下一代几乎全长的HIV-1基因组的测序.
- 对应的染色体整合部位的分析.
- 对宿主基因组特征的研究,包括染色质可访问性和表观遗传标记.
主要成果:
- 精英控制器中的临时病毒储存通常包括完整的HIV-1序列的寡克隆到近单克隆集群.
- 在不同的基因组部位整合完整的前病毒序列,最好是在19号染色体上的中心卫星DNA或特定基因中.
- 整合地点距离转录起点和可访问的染色体更远,
结论:
- 一个独特的预病毒储库配置,以整合到异色区域为特征,是自然HIV-1控制的结构相关.
- 病毒储备的质量, 不仅仅是数量, 是实现功能性HIV-1治愈的关键特征.
- 在一个精英控制器中没有可检测的完整的前病毒DNA,这表明在罕见的情况下可以杀菌治疗.
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