艾滋病毒从细胞传播到细胞传播允许持续复制,尽管抗逆转录病毒疗法
Alex Sigal1, Jocelyn T Kim, Alejandro B Balazs
1Division of Biology, California Institute of Technology, Pasadena, California 91125, USA.
Nature
|August 19, 2011
概括
感染人类免疫缺陷病毒 (HIV) 的多细胞感染会减少药物敏感性,而不会发生突变. 细胞间传播是关键的传播途径,在抗逆转录病毒疗法期间允许HIV复制,这可能会阻碍治愈.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 药理学 药理学是指药理学的学科.
背景情况:
- 抗逆转录病毒疗法 (ART) 抑制了人类免疫缺陷病毒 (HIV) 复制,但药物不敏感的储备仍然存在.
- 延迟和持续复制是这种持久的HIV储存机制的建议.
研究的目的:
- 研究一种在ART期间持续HIV复制的新机制.
- 探索每细胞多种感染和细胞间传播如何促进药物耐药性.
主要方法:
- 一个模型的实验验证,其中每个细胞的多个感染可以在没有突变的情况下降低药物敏感性.
- 评估细胞间艾滋病毒传播的药物敏感性与在诺福维尔和埃法维伦兹的存在下细胞自由的艾滋病毒感染.
- 在临床药物度下,利用随机感染模型来分析从细胞传播到细胞传播的HIV复制.
主要成果:
- 每个细胞的多次感染可以降低艾滋病毒对特诺福维尔的敏感性,而不需要耐药突变.
- 与无细胞感染相比,细胞对细胞的艾滋病毒传播对抗逆转录病毒药物tenofovir和efavirenz的敏感性明显较低.
- 通过细胞间传播的HIV复制可以在临床药物度的存在下间歇地发生,而没有显著的突变积累.
结论:
- 每个细胞的多种感染和细胞间传播代表了在ART期间持续的HIV复制的重要机制.
- 这种传播方式可能导致药物敏感性降低,可能导致治疗失败,并导致病毒持久性.
- 细胞间传播可能是治愈艾滋病毒感染的障碍,并可能对免疫系统产生不利影响.
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