Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
Virol J. 2011 Jul 29;8:376. doi: 10.1186/1743-422X-8-376.
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.
基孔肯雅病毒（CHIKV）是一种通过蚊子传播的甲病毒，最近在非洲热带地区、印度洋盆地和东南亚引发了几次大规模的关节炎疾病爆发/流行。这种重新出现的事件是由 CHIKV 对这种病毒的一种新的重要蚊子媒介（白纹伊蚊）的遗传适应性（E1-A226V 取代）促成的。然而，解释 E1-A226V 突变对 CHIKV 在该媒介中适应性的积极影响的分子机制在很大程度上仍然未知。此前我们证明，E1-A226V 取代也与胆固醇耗竭细胞中 CHIKV 生长减弱有关。
在这项研究中，我们使用了一组在对胆固醇的敏感性上有所不同的 CHIKV 克隆，研究了胆固醇依赖性和白纹伊蚊感染性之间可能存在的关系。
我们证明这两种表型之间没有明确的机制相关性。我们还表明，E1-A226V 突变增加了 CHIKV 融合反应对 pH 值的依赖性；然而，随后的遗传分析未能支持 CHIKV 对较低 pH 值的依赖性与蚊子感染性表型之间的关联。
E1-A226V 突变可能在 CHIKV 生命周期的不同阶段起作用，影响病毒的多种功能。
