Chikungunya virus adaptation to Aedes albopictus mosquitoes does not correlate with acquisition of cholesterol dependence or decreased pH threshold for fusion reaction.
Chikungunya virus adaptation to Aedes albopictus mosquitoes does not correlate with acquisition of cholesterol dependence or decreased pH threshold for fusion reaction.
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DOI：
10.1186/1743-422x-8-376
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发表时间：
2011-07-29
期刊：
影响因子：
4.8
通讯作者：
Higgs S
中科院分区：
文献类型：
--
作者：
Tsetsarkin KA;McGee CE;Higgs S
基孔肯雅病毒（CHIKV）是一种由蚊子传播的甲病毒，最近在非洲热带、印度洋盆地和东南亚引起了几次大规模的关节炎疾病爆发/流行。 CHIKV 对该病毒的新重要蚊子载体的遗传适应（E1-A226V 替换）促进了这一重新出现事件；白纹伊蚊。然而，解释 E1-A226V 突变对该载体中 CHIKV 适应性的积极影响的分子机制仍然很大程度上未知。之前我们证明 E1-A226V 取代也与胆固醇耗尽的细胞中 CHIKV 生长减弱有关。在这项研究中，我们使用一组对胆固醇敏感性不同的 CHIKV 克隆，研究了胆固醇依赖性和伊蚊之间可能的关系。白纹伊蚊传染性。我们证明这两种表型之间没有明显的机制相关性。我们还表明，E1-A226V 突变增加了 CHIKV 融合反应的 pH 依赖性；然而，随后的遗传分析未能支持 CHIKV 对较低 pH 值的依赖与蚊子感染表型之间的关联。 E1-A226V突变可能作用于CHIKV生命周期的不同步骤，影响病毒的多种功能。
Chikungunya virus (CHIKV) is a mosquito transmitted alphavirus that recently caused several large scale outbreaks/epidemics of arthritic disease in tropics of Africa, Indian Ocean basin and South-East Asia. This re-emergence event was facilitated by genetic adaptation (E1-A226V substitution) of CHIKV to a newly significant mosquito vector for this virus; Aedes albopictus. However, the molecular mechanism explaining the positive effect of the E1-A226V mutation on CHIKV fitness in this vector remains largely unknown. Previously we demonstrated that the E1-A226V substitution is also associated with attenuated CHIKV growth in cells depleted by cholesterol. In this study, using a panel of CHIKV clones that varies in sensitivity to cholesterol, we investigated the possible relationship between cholesterol dependence and Ae. albopictus infectivity. We demonstrated that there is no clear mechanistic correlation between these two phenotypes. We also showed that the E1-A226V mutation increases the pH dependence of the CHIKV fusion reaction; however, subsequent genetic analysis failed to support an association between CHIKV dependency on lower pH, and mosquito infectivity phenotypes. the E1-A226V mutation probably acts at different steps of the CHIKV life cycle, affecting multiple functions of the virus.