允许的二次基因突变使得流感病毒对oseltamivir的耐药性演变成为可能
Jesse D Bloom1, Lizhi Ian Gong, David Baltimore
1Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
概括
在His274-->Tyr274突变赋予流感病毒的oseltamivir耐药性. 二次突变使这种耐药菌株能够通过恢复病毒适应性来占主导地位.
科学领域:
- 病毒学 病毒学
- 抗微生物耐药性 抗微生物耐药性
背景情况:
- 在N1流感神经氨基酶中的His274-->Tyr274 (H274Y) 突变赋予了对oseltamivir的耐药性.
- 此前,人们认为这种突变会降低病毒的适应性,阻碍其传播.
研究的目的:
- 从2007-2008年开始,调查含有H274Y的季节性H1N1流感病毒迅速流行背后的机制.
- 了解在存在H274Y突变时病毒健康如何恢复.
主要方法:
- 对细胞表面神经氨基酶水平与H274Y突变相关的分析.
- 确定补偿H274Y.引起的适应性缺陷的二次突变.
主要成果:
- H274Y突变减少了到达细胞表面的神经氨基酶的数量.
- 确定了能够抵消这种缺陷并恢复病毒健康的二次突变.
- 这些允许性突变在季节性H1N1分离物中H274Y广泛出现之前发生.
结论:
- 奥塞尔塔米维尔耐药性的演变是由先前存在的允许突变促进的,允许对H274Y突变的耐受性.
- 了解这种进化途径可能有助于预测其他流感菌株未来的奥塞尔塔米维尔耐药性发展.
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