Data Mining Department, Institute for Infocomm Research, Fusionopolis, Singapore, Singapore.
PLoS One. 2010 Feb 26;5(2):e9291. doi: 10.1371/journal.pone.0009291.
After two decades of quiescence, epidemic resurgence of Chikungunya fever (CHIKF) was reported in Africa, several islands in the Indian Ocean, South-East Asia and the Pacific causing unprecedented morbidity with some cases of fatality. Early phylogenetic analyses based on partial sequences of Chikungunya virus (CHIKV) have led to speculation that the virus behind recent epidemics may result in greater pathogenicity. To understand the reasons for these new epidemics, we first performed extensive analyses of existing CHIKV sequences from its introduction in 1952 to 2009. Our results revealed the existence of a continuous genotypic lineage, suggesting selective pressure is active in CHIKV evolution. We further showed that CHIKV is undergoing mild positive selection, and that site-specific mutations may be driven by cell-mediated immune pressure, with occasional changes that resulted in the loss of human leukocyte antigen (HLA) class I-restricting elements. These findings provide a basis to understand Chikungunya virus evolution and reveal the power of post-genomic analyses to understand CHIKV and other viral epidemiology. Such an approach is useful for studying the impact of host immunity on pathogen evolution, and may help identify appropriate antigens suitable for subunit vaccine formulations.
在沉寂了二十年之后，基孔肯雅热（CHIKF）在非洲、印度洋的几个岛屿、东南亚和太平洋地区再次爆发，造成了前所未有的发病率，有些病例还出现了死亡。早期基于基孔肯雅病毒（CHIKV）部分序列的系统进化分析表明，近期流行的病毒可能具有更高的致病性。为了了解这些新流行的原因，我们首先对 1952 年至 2009 年引入的现有 CHIKV 序列进行了广泛的分析。我们的结果表明存在连续的基因型谱系，表明选择压力在 CHIKV 的进化中起作用。我们进一步表明，CHIKV 正在经历温和的正选择，并且特定位点的突变可能是由细胞介导的免疫压力驱动的，偶尔的变化导致人类白细胞抗原（HLA）I 类限制元件的丢失。这些发现为了解基孔肯雅病毒的进化提供了基础，并揭示了后基因组分析在了解 CHIKV 和其他病毒流行病学方面的强大功能。这种方法有助于研究宿主免疫对病原体进化的影响，并可能有助于确定适合亚单位疫苗配方的适当抗原。
