艾滋病毒通过内分细胞分裂和与内分细胞的动氨酸依赖融合进入细胞
Kosuke Miyauchi1, Yuri Kim, Olga Latinovic
1Institute of Human Virology and Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Cell
|May 5, 2009
概括
人类免疫缺陷病毒 (HIV-1) 通过内细胞突变进入细胞,而不是通过直接的血膜融合. 完整的融合发生在内体内,这个过程依赖于病毒葡萄糖蛋白和dynamin.
科学领域:
- 病毒学 病毒学
- 细胞生物学 细胞生物学
- 传染性疾病 传染性疾病
背景情况:
- 包裹病毒通常通过与内分泌体的pH依赖的融合进入细胞.
- 对于像HIV-1这样的pH独立病毒的进入机制,特别是融合部位,仍然未被定义.
- 以前的假设表明,HIV-1与宿主细胞的血直接融合.
研究的目的:
- 确定HIV-1进入和融合的确切地点和机制.
- 研究细胞内和细胞内对HIV-1感染的作用.
- 为了确定HIV-1融合对特定细胞因子 (如dynamin) 的依赖.
主要方法:
- 基于人群的病毒内容传递到细胞质中的测量.
- 单个病毒颗粒的时间分辨率成像.
- 使用dynasore,一个dynamin抑制剂的抑制研究.
主要成果:
- 证明完整的HIV-1融合发生在内体内,而不是在血上.
- 血中的融合在脂质混合阶段停滞不前.
- 在内体细胞融合之前,HIV-1 经历受体介导的内细胞分裂,从而减少了表位暴露.
结论:
- 艾滋病毒-1 感染是通过内细胞分裂 (endocytosis) 开始的,随后是细胞内内基因组内的融合.
- 内体融合依赖于病毒包膜糖蛋白和宿主细胞蛋白质dynamin.
- 这种机制有助于HIV-1通过在进入过程中最大限度地减少表面表皮层暴露来逃避免疫检测.
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