潜存储库中的具有复制能力的非诱导性前病毒增加了治愈HIV-1的障碍
Ya-Chi Ho1, Liang Shan, Nina N Hosmane
1Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Cell
|November 19, 2013
概括
潜伏的HIV-1前病毒存在于休息的CD4 (((+) T细胞中,阻碍了治愈. 发现完整的,非诱导的前病毒具有复制能力,显著增加了潜在储库的估计大小.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 抗逆转录病毒疗法 (ART) 无法治愈HIV-1感染,原因是休息的CD4 ((+) T细胞中持续存在的潜伏前病毒.
- T细胞激活诱导<1%的潜伏前病毒释放传染性病毒,非诱导前病毒通常被认为是有缺陷的.
研究的目的:
- 描述非诱导潜伏HIV-1前病毒的性质和复制能力.
- 重新评估潜伏HIV-1储存库的大小及其对实现治愈的影响.
主要方法:
- 从接受治疗的HIV-1患者中分析了213个非诱导的前病毒克隆.
- 直接测序和基因组合成以重建全长完整的原病毒克隆.
- 评估长终端重复 (LTR) 功能和病毒生长动力学.
主要成果:
- 11.7%的非诱导前病毒克隆具有完整的基因组与正常的LTR功能,与88.3%含有缺陷的基因组形成鲜明对比.
- 重建完整的非诱导型病毒表现出与诱导型病毒相比的生长动力学.
- 发现非诱导的前病毒与未甲基化促进体集成到活性转录单元中.
结论:
- 在潜存储库中存在具有复制能力的非诱导HIV-1前病毒.
- 潜伏的HIV-1储备可能比以前估计的要大得多,可能高达60倍.
- 这些完好无损的前病毒的存在构成了治愈HIV-1的重大障碍.
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