在潜伏和活跃感染期间的HIV-1整合景观
Lillian B Cohn1, Israel T Silva2, Thiago Y Oliveira1
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
Cell
|January 31, 2015
概括
作为治愈障碍的HIV-1储存体,主要存在于具有缺陷前病毒的静止CD4 ((+) T细胞中. 分裂的T细胞含有非完好无损的病毒,这表明针对潜伏的HIV-1储存库的策略.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 遗传学 是一个遗传学.
背景情况:
- 治愈HIV-1的主要障碍是CD4 ((+) T细胞内潜伏的前病毒储备.
- 了解这些潜伏感染细胞的特征对于开发有效的根除策略至关重要.
研究的目的:
- 在不同患者群体中研究HIV-1的整合特征,以描述潜藏的储存库.
- 为了确定克隆扩张和非扩张T细胞内的前病毒状态.
主要方法:
- 对来自病毒病患者,抗逆转录病毒疗法患者和病毒病控制者的CD4 (((+) T细胞中的HIV-1整合部位的分析.
- 对T细胞克隆进行完整的前病毒检测.
- 调查集成地点偏好,包括Alu重复.
主要成果:
- 克隆扩张的T细胞占整合的多数,在治疗期间增加,但不含完整的病毒.
- 单个集成事件的细胞在治疗中减少,幸存细胞显示在静默基因组区域集成的丰富.
- 艾滋病毒-1整合显示出对Alu重复的偏好,这些重复形成了局部热点.
结论:
- 分裂,克隆扩张的T细胞携带有缺陷的前病毒.
- 具有复制能力的HIV-1储存体主要位于相对静止的CD4 ((+) T细胞中.
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