Singapore Immunology Network, Agency for Science, Technology and Research, Biopolis, Singapore.
J Immunol. 2010 May 15;184(10):5903-13. doi: 10.4049/jimmunol.0904181. Epub 2010 Apr 19.
Chikungunya virus (CHIKV) is an alphavirus that causes chronic and incapacitating arthralgia in humans. To date, interactions between the immune system and the different stages of the virus life cycle remain poorly defined. We demonstrated for the first time that CHIKV Ags could be detected in vivo in the monocytes of acutely infected patients. Using in vitro experimental systems, whole blood and purified monocytes, we confirmed that monocytes could be infected and virus growth could be sustained. CHIKV interactions with monocytes, and with other blood leukocytes, induced a robust and rapid innate immune response with the production of specific chemokines and cytokines. In particular, high levels of IFN-alpha were produced rapidly after CHIKV incubation with monocytes. The identification of monocytes during the early phase of CHIKV infection in vivo is significant as infected monocyte/macrophage cells have been detected in the synovial tissues of chronically CHIKV-infected patients, and these cells may behave as the vehicles for virus dissemination. This may explain the persistence of joint symptoms despite the short duration of viremia. Our results provide a better understanding on the basic mechanisms of infection and early antiviral immune responses and will help in the development of future effective control strategies.
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。迄今为止,免疫系统与病毒生命周期的不同阶段之间的相互作用仍未得到明确界定。我们首次证明,在急性感染患者的单核细胞中可以在体内检测到 CHIKV 抗原。使用体外实验系统、全血和纯化的单核细胞,我们证实单核细胞可以被感染并且可以维持病毒生长。CHIKV 与单核细胞和其他血液白细胞的相互作用诱导了强烈而快速的先天免疫反应,产生了特异性趋化因子和细胞因子。特别是,在 CHIKV 与单核细胞孵育后,IFN-α的水平迅速升高。在体内 CHIKV 感染的早期阶段鉴定单核细胞具有重要意义,因为在慢性 CHIKV 感染患者的滑膜组织中已经检测到感染的单核细胞/巨噬细胞,并且这些细胞可能作为病毒传播的载体。这可以解释尽管病毒血症持续时间短,但关节症状仍持续存在的原因。我们的研究结果提供了对感染和早期抗病毒免疫反应的基本机制的更好理解,并将有助于开发未来有效的控制策略。