肠道病毒71型2A蛋白酶抵抗I型干扰素诱导的抗病毒作用

发布时间：2018-04-05 13:14

  本文选题：先天性免疫　切入点：手足口病　出处：《安徽理工大学》2012年硕士论文

【摘要】：手足口病(hand-foot-mouth disease, HFMD)是由数种肠道病毒引起的全球性的传染病。多发生于5岁以下儿童,可引起手、足、口腔、臀部等部位的疱疹。通常情况下,手足口病发病较轻,少年儿童和成人感染为无症状携带者,但能够传播病毒。病程约为7至10天,少数患儿可引起心肌炎、肺水肿、无菌性脑膜脑炎等并发症,个别重症患儿因病情发展快而导致死亡 流行病学结果显示HFMD以柯萨奇病毒A16型(Cox A16)和肠道病毒71型(EV71)最为常见,CA16引起的HFMD预后较好,多为散发,极少导致HFMD的大规模暴发。EV71感染引起重症和死亡病例较多见。 先天性免疫(innate immunity)指个体出生时即具备,作用范围广,不针对特定抗原的免疫能力,所以也称为非特异性免疫(nonspecific immunity)。在机体的防御机制中具有重要作用,是抵抗病原微生物感染的第一道防线,是机体对多种抗原物质的生理性排斥反应。 先天性免疫应答(innate immune response)的一个重要方面是Ⅰ型干扰素(type I interferon)的合成和分泌。Ⅰ型干扰素由多种细胞在病毒感染时产生,具有早期抗病毒作用,可与细胞膜上的特异性受体结合,并且可以引发级联性的信号放大效应,最终诱导靶细胞产生特异的抗病毒蛋白。 从HFMD的发病特点来看,其潜伏期为2-7天,死亡病例病程约3-5天,在如此短的病程中,机体对EV71病毒感染的获得性免疫应答尚未建立。因此,病毒感染的宿主先天性免疫可能在病毒引起重症和死亡病例的原因中发挥重要的作用。 为了解EV71对先天性免疫中的干扰素系统的作用,本研究使用表达GFP的重组HSV-1评价Ⅰ型干扰素(α,β)作用。干扰素(α,p)作用于培养的HeLa细胞,可以诱导HeLa细胞产生抗病毒作用而抑制HSV-1的GFP的表达。同样,发现EV71病毒也可以在干扰素诱导产生抗病毒蛋白的HeLa细胞中增殖,说明EV71能够抵抗干扰素(α,β)的抗病毒作用。 为进一步了解EV71抵抗干扰素的机制,我们将EV71的2A蛋白酶转染入HeLa细胞,发现2A抑制了干扰素(α、β)的作用,使HSV-1复制明显增强。因此,EV71病毒可能通过干扰Ⅰ型干扰素的作用而逃避宿主的免疫防御,从而造成病毒的持续感染。
[Abstract]:Hand, foot and mouth disease (HFMD) is a global infectious disease caused by several enterovirus.Most cases occur in children under 5 years old, can cause hand, foot, mouth, buttocks and other parts of the herpes.Hand-foot-mouth disease is usually mild, infecting children and adults as asymptomatic carriers but capable of spreading the virus.The course of disease is about 7 to 10 days, a few children can cause myocarditis, pulmonary edema, aseptic meningoencephalitis and other complications.The epidemiological results showed that HFMD caused by coxsackie virus A16 (Coxsackie virus A16) and enterovirus 71 (EV71) were the most common. Most of them were sporadic.Innate immunity refers to an individual born with a wide range of functions, not specific to the immune ability of specific antigen, so it is also called nonspecific immunity.It plays an important role in the defense mechanism of the organism and is the first line of defense against the infection of pathogenic microorganisms. It is also the physiological rejection of many antigens.An important aspect of congenital immune response immune response is the synthesis and secretion of type 鈪，

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