寨卡病毒使用多个伪结结构产生非编码RNA,该结构混细胞外核酶
Benjamin M Akiyama1, Hannah M Laurence1,2,3, Aaron R Massey4
1Department of Biochemistry and Molecular Genetics, University of Colorado Denver School of Medicine, Aurora, CO 80045, USA.
Science (New York, N.Y.)
|December 10, 2016
概括
寨卡病毒 (ZIKV) 通过劫持细胞酶产生亚基因组黄病毒RNA (sfRNA). 了解这种涉及xrRNA结构的机制是对抗ZIKV相关的先天缺陷的关键.
科学领域:
- 病毒学
- 分子生物学
- 核糖核酸生物学
背景情况:
- 寨卡病毒 (ZIKV) 爆发与胎儿小头症有关,需要对其分子感染机制进行研究.
- 相关的黄病毒在感染宿主中产生致病性非编码的亚基因组黄病毒RNA (sfRNA).
- 这些sfRNAs是在病毒利用结构化RNAs (称为xrRNAs) 与细胞外核酶相互作用时产生的.
研究的目的:
- 研究ZIKV在各种细胞类型中的sfRNAs的产生.
- 阐明特定RNA结构 (xrRNAs) 在ZIKV sfRNA生物发生和外核酶耐药性的作用.
- 了解ZIKV致病性的分子基础,并确定潜在的治疗点.
主要方法:
- 在ZIKV感染的子上皮细胞,人类上皮细胞,小鼠神经元和蚊子细胞中检测和表征sfRNAs.
- 在体外测试以评估突变对xrRNA结构和外核酶耐药性的影响.
- 对ZIKV xrRNA进行结构分析,以了解其与细胞因子的相互作用.
主要成果:
- ZIKV感染导致多种细胞类型的sfRNAs产生,包括灵长类动物,人类,老鼠和昆虫细胞.
- 一个特定的复杂RNA折叠 (xrRNA) 负责ZIKV sfRNA的产生.
- 破坏xrRNA结构的突变显著降低了体外核酶耐药性和感染期间的sfRNA形成.
结论:
- 通过对细胞外核酶产生抗性,ZIKV xrRNA 结构对于 sfRNA 生产至关重要.
- 这种sfRNA生成机制在致病性黄病毒中很可能存在.
- 阐明ZIKV xrRNA结构提供了有关弗拉维病毒病原性和潜在干预策略的见解.
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