SOCS蛋白在肠道病毒感染过程中的作用

发布时间：2018-07-24 15:49

【摘要】：手足口病毒71型(EV71)是一种常见的肠道病毒,病毒颗粒是二十面体的球形、对称结构,其遗传物质是单链正股RNA,且仅有一个开放阅读框。该病毒好发生于婴幼儿(5岁以下),多为自限性疾病,少数毒株会引起神经系统疾病,所以对于该种病毒的致病机理以及抗病毒靶点的研究就显得至关重要。SOCS(suppressor of cytokine signaling)蛋白,作为细胞因子信号通路抑制蛋白的成员,目前认为该蛋白家族可以调节LIF(leukemia inhibitory factor)、G-CSF(granulocyte colony-stimulating factor)、IL-6(interleukin-6)、IL-10(interleukin-10)、IFN-λ(interferon-λ)等30多种细胞因子,而这些因子是机体抵抗入侵的外来病原体的主要免疫防御反应。病毒在感染宿主的过程中可以通过劫持宿主中的SOCS蛋白,从而对细胞中的JAK/STAT、NF-κB等与抗病毒因子调控相关的信号通路以及对T细胞的分化的调控调节病毒感染。本文主要讨论SOCS蛋白通过调控JAK-STAT、NF-κB等信号通路,在肠道病毒感染过程中发挥的作用和作用机制。此次实验主要是从体外(RD细胞中)和体内(乳鼠肌肉组织和血液中)两个方面观察SOCS蛋白是否与病毒感染相关。在RD细胞中,我们发现感染病毒后细胞内的SOCS蛋白会特异性的高表达,p STAT、模式识别受体RIG1蛋白也会产生相应的变化。Shut down SOCS蛋白后,可以观察到细胞中病毒的复制能力下降,并且抗病毒因子OAS2、MX1、IL28、IL29在敲除了SOCS蛋白的细胞中的表达也会比正常的细胞中高,这些都间接证明了EV71会通过将SOCS蛋白升高以达到降低抗病毒因子的表达、帮助病毒的感染等目的。同时,我们在感染EV71的乳鼠的肌肉组织中也检测出同样的变化趋势。这个结果显示,SOCS蛋白在病毒感染的过程中主要起到了帮助病毒感染宿主并抑制干扰素信号通路的激活的作用。
[Abstract]:Hand foot and mouth disease virus type 71 (EV71) is a common enterovirus with globular and symmetrical structure of icosahedron. Its genetic material is single-stranded orthoplast RNAs with only one open reading frame. The virus occurs in infants (under 5 years of age) and is mostly self-limited disease. A few strains can cause nervous system diseases, so it is very important to study the pathogenic mechanism and antiviral target of the virus. SOCS (suppressor of cytokine signaling) protein is very important. As a member of cytokine signaling pathway inhibitory protein, it is believed that this protein family can regulate more than 30 cytokines, such as LIF (leukemia inhibitory factor) G-CSF (granulocyte colony-stimulating factor), IL-6 (interleukin-6), IL-10 (interleukin-10), IFN- 位 (interferon- 位), and these cytokines are the main immune defense response of the body against invading foreign pathogens. The virus can hijack the SOCS protein in the host during the process of infection, thus regulating the signal pathway related to antiviral factor regulation and the regulation of T cell differentiation in the cell, such as JAK / STATNF- 魏 B. This paper mainly discusses the role and mechanism of SOCS protein in the process of enterovirus infection by regulating JAK-STAT- NF- 魏 B signaling pathway. In this experiment, we observed whether SOCS protein was related to virus infection in vitro (Rd cells) and in vivo (muscle tissue and blood of neonatal rats). In Rd cells, we found that the specific expression of SOCS protein in Rd cells was high after infection, and the pattern recognition receptor RIG1 protein had a corresponding change .Shut down SOCS protein, we found that the replication ability of the virus in the cells decreased. The expression of the antiviral factor OAS2MX1 / IL28 / IL29 was also higher in the cells that knocked out the SOCS protein than in the normal cells, which indirectly proved that EV71 can reduce the expression of antiviral factors and help the virus infection by increasing the SOCS protein. We also detected a similar trend in muscle tissue of EV71 infected suckling mice. These results suggest that the SOCS protein plays an important role in helping the host and inhibiting the activation of interferon signaling pathway during viral infection.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R512.5

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