Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore.
J Virol. 2012 Dec;86(23):13005-15. doi: 10.1128/JVI.01780-12. Epub 2012 Sep 26.
Chikungunya virus (CHIKV) is an alphavirus which causes chronic and incapacitating arthralgia in humans. Although previous studies have shown that antibodies against the virus are produced during and after infection, the fine specificity of the antibody response against CHIKV is not known. Here, using plasma from patients at different times postinfection, we characterized the antibody response against various proteins of the virus. We have shown that the E2 and E3 glycoproteins and the capsid and nsP3 proteins are targets of the anti-CHIKV antibody response. Moreover, we have identified the different regions in these proteins which contain the linear epitopes recognized by the anti-CHIKV antibodies and determined their structural localization. Data also illustrated the effect of a single K(252)Q amino acid change at the E2 glycoprotein that was able to influence antibody binding and interaction between the antibodies and epitope because of the changes of epitope-antibody binding capacity. This study provides important knowledge that will not only aid in the understanding of the immune response to CHIKV infection but also provide new knowledge in the design of modern vaccine development. Furthermore, these pathogen-specific epitopes could be used for future seroepidemiological studies that will unravel the molecular mechanisms of human immunity and protection from CHIKV disease.
基孔肯雅病毒（CHIKV）是一种甲病毒，可导致人类慢性和使人丧失能力的关节炎。尽管先前的研究表明，在感染期间和之后会产生针对该病毒的抗体，但针对 CHIKV 的抗体反应的精细特异性尚不清楚。在这里，我们使用感染后不同时间的患者血浆，对针对病毒的各种蛋白的抗体反应进行了表征。我们已经表明，E2 和 E3 糖蛋白以及衣壳和 nsP3 蛋白是抗 CHIKV 抗体反应的靶标。此外，我们还鉴定了这些蛋白中包含线性表位的不同区域，这些表位被抗 CHIKV 抗体识别，并确定了它们的结构定位。数据还说明了 E2 糖蛋白上单个 K(252)Q 氨基酸变化的影响，该变化能够由于表位-抗体结合能力的变化而影响抗体结合和抗体与表位之间的相互作用。这项研究提供了重要的知识，不仅有助于了解对 CHIKV 感染的免疫反应，而且为现代疫苗开发的设计提供了新的知识。此外，这些病原体特异性表位可用于未来的血清流行病学研究，以揭示人类免疫和对 CHIKV 疾病的保护的分子机制。
