Institute for Human Infections and Immunity, Center for Tropical Diseases, and Department of Pathology, University of Texas Medical Branch, Galveston, Texas, United States of America.
PLoS Pathog. 2011 Dec;7(12):e1002412. doi: 10.1371/journal.ppat.1002412. Epub 2011 Dec 8.
The adaptation of Chikungunya virus (CHIKV) to a new vector, the Aedes albopictus mosquito, is a major factor contributing to its ongoing re-emergence in a series of large-scale epidemics of arthritic disease in many parts of the world since 2004. Although the initial step of CHIKV adaptation to A. albopictus was determined to involve an A226V amino acid substitution in the E1 envelope glycoprotein that first arose in 2005, little attention has been paid to subsequent CHIKV evolution after this adaptive mutation was convergently selected in several geographic locations. To determine whether selection of second-step adaptive mutations in CHIKV or other arthropod-borne viruses occurs in nature, we tested the effect of an additional envelope glycoprotein amino acid change identified in Kerala, India in 2009. This substitution, E2-L210Q, caused a significant increase in the ability of CHIKV to develop a disseminated infection in A. albopictus, but had no effect on CHIKV fitness in the alternative mosquito vector, A. aegypti, or in vertebrate cell lines. Using infectious viruses or virus-like replicon particles expressing the E2-210Q and E2-210L residues, we determined that E2-L210Q acts primarily at the level of infection of A. albopictus midgut epithelial cells. In addition, we observed that the initial adaptive substitution, E1-A226V, had a significantly stronger effect on CHIKV fitness in A. albopictus than E2-L210Q, thus explaining the observed time differences required for selective sweeps of these mutations in nature. These results indicate that the continuous CHIKV circulation in an A. albopictus-human cycle since 2005 has resulted in the selection of an additional, second-step mutation that may facilitate even more efficient virus circulation and persistence in endemic areas, further increasing the risk of more severe and expanded CHIK epidemics.
基孔肯雅热病毒（CHIKV）适应新的传播媒介——白纹伊蚊，是其自 2004 年以来在世界许多地区多次引发大规模关节炎疾病流行的主要因素。虽然 CHIKV 对 A. albopictus 的最初适应步骤确定涉及 E1 包膜糖蛋白中的 A226V 氨基酸取代，该取代于 2005 年首次出现，但在该适应性突变在几个地理位置被趋同选择后，人们很少关注 CHIKV 的后续进化。为了确定 CHIKV 或其他节肢动物传播病毒的第二步适应性突变是否在自然界中发生选择，我们测试了 2009 年在印度喀拉拉邦发现的另一个包膜糖蛋白氨基酸变化的影响。该取代 E2-L210Q 显著增加了 CHIKV 在白纹伊蚊中形成播散性感染的能力，但对 CHIKV 在替代蚊媒 A. aegypti 或脊椎动物细胞系中的适应性没有影响。使用感染性病毒或表达 E2-210Q 和 E2-210L 残基的病毒样复制子颗粒，我们确定 E2-L210Q 主要作用于 A. albopictus 中肠上皮细胞的感染水平。此外，我们观察到最初的适应性取代 E1-A226V 对 CHIKV 在 A. albopictus 中的适应性比 E2-L210Q 具有更强的影响，从而解释了在自然界中这些突变选择清扫所需的时间差异。这些结果表明，自 2005 年以来，CHIKV 在 A. albopictus-人类循环中的持续循环导致选择了另一个第二步突变，这可能使病毒在流行地区的循环和持续存在更加高效，进一步增加了更严重和更广泛的 CHIK 流行的风险。
