肠道病毒71型3A蛋白通过增强外泌体的分泌参与病毒感染的研究

已有研究表明外泌体在HIV等病毒感染的过程中发挥了重要的调控作用，但目前尚无外泌体在EV71感染过程中的报道。本课题组发现在EV71感染过程中，外泌体通过携带病毒成份，能直接感染神经母细胞瘤细胞SK-N-SH。同时，我们首次发现EV71的非结构蛋白3A能够影响外泌体的分泌，并锚定于外泌体。本项目拟进一步研究在EV71感染SK-N-SH细胞的过程中， EV71 3A蛋白对外泌体产生过程的调控作用及其分子机制，以及携带3A蛋白的外泌体在病毒感染中的作用。在此基础上，利用EV71感染动物模型——一日龄BALB/C鼠验证3A蛋白促进外泌体分泌、参与感染的作用和机制。将EV71感染的手足口病患者分为轻症和重症两组，通过logistic回归分析患者血清等量外泌体中的3A蛋白含量与疾病发展的相关性，评价其作为疾病发展的预警指标。本项目将阐明EV71通过外泌体途径感染细胞是其致病的一种新机制。

Studies have shown that exosomes play an important role in the regulation of virus infection, such as HIV, but there is no report about the exosomes in the process of EV71 infection. We have found that in the process of enterovirus 71 (EV71) infection, exosomes carrying virus components can infect neuroblastoma cells SK-N-SH. At the same time, we first found that EV71 non-structural protein 3A can affect the secretion of exosomes, and anchored in the exosomes. We will investigate the role and molecular mechanism of 3A protein regulating the secretion of the exosomes, and the function of 3A+ exosome during EV71 infection. On this basis, by using of animal models of EV71 infection, we want to verify that 3A protein could promote the secretion of exosomes, participate in EV71 infection in one-day-old BALB/C rats. Hand, foot and mouth disease (HFMD) patients infected by EV71 were divided into two groups, patients with mild and severe symptom. Regression analysis method are used in the study of correlation between the level of 3A protein in equal exosomes and the development of the disease. We will evaluate the level of 3A protein in equal exosomes as a warning indicator of disease development. This study will clarify that the EV71 infected cells through exosomes is a new pathogenic mechanism.