腺病毒血清型5的hexon介导肝脏基因转移
Simon N Waddington1, John H McVey, David Bhella
1Department of Haematology, Haemophilia Centre and Haemostasis Unit, Royal Free and University College Medical School, London NW3 2PF, UK.
Cell
|February 13, 2008
概括
腺病毒通过凝血因子X与子蛋白结合,而不是纤维蛋白,向肝细胞. 这种相互作用是肝脏基因转移的关键,揭示了子体内子体的新作用.
科学领域:
- 病毒学 病毒学
- 基因治疗 基因治疗
- 分子生物学分子生物学
背景情况:
- 腺病毒是常见的基因转移载体.
- 腺病毒向肝脏限制了它们的有效性.
- 科克萨基病毒和腺病毒受体 (CAR) 在体外调解细胞结合,但在体内不调解肝脏转导.
研究的目的:
- 为了阐明腺病毒肝脏转导的机制.
- 为了确定负责向肝脏的腺病毒组件.
- 为了研究凝血因子X (FX) 在腺病毒肝脏感染中的作用.
主要方法:
- 研究了FX和腺病毒血清型5 (Ad5) 之间的相互作用.
- 使用结构分析绘制了Ad5上FX的绑定位置.
- 评估了FX Gla域和血清蛋白酶域在肝脏感染中的作用.
- 在多种人类腺病毒血清型中测试了结合.
主要成果:
- FX 结合到 Ad5 六子蛋白,而不是纤维蛋白.
- 这种相互作用涉及FX Gla域和Ad5六边形超变区.
- 结合FX发生在多种人类腺病毒血清型中.
- 通过FX-Ad5复合体的肝脏感染是由FX血清蛋白酶域中的氨酸结合异位体介导的.
结论:
- 腺病毒肝脏转导是由FX与赫克逊蛋白结合的媒介.
- 这种相互作用绕过了CAR受体路径.
- 赫克森蛋白在促进体内肝脏基因转移方面发挥了意想不到的作用.
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