Coxsackievirus B3 inhibits antigen presentation in vivo, exerting a profound and selective effect on the MHC class I pathway.
Coxsackievirus B3 inhibits antigen presentation in vivo, exerting a profound and selective effect on the MHC class I pathway.
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DOI：
10.1371/journal.ppat.1000618
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发表时间：
2009-10
期刊：
影响因子：
6.7
通讯作者：
Whitton JL
中科院分区：
文献类型：
--
作者：
Kemball CC;Harkins S;Whitmire JK;Flynn CT;Feuer R;Whitton JL
许多病毒编码的蛋白质的主要功能是逃避或禁用宿主T细胞反应。然而，大多数病毒容易被宿主T细胞检测到，并诱导相对较强的T细胞应答。在此，我们采用转基因的CD 4+和CD 8 + T细胞作为传感器，以评估在体外和体内的抗原呈递柯萨奇病毒B3（CVB 3），我们表明，这种病毒几乎完全抑制抗原呈递通过MHC I类途径，从而逃避CD 8 + T细胞免疫。相反，CVB 3编码的MHC II类表位的呈递是相对不受阻碍的，并且CVB 3诱导体内CD 4 + T细胞应答，根据几个标准，这些应答是表型正常的。这些细胞表现出效应表型，并成熟为多功能CVB 3特异性记忆CD 4 + T细胞，这些细胞在攻击感染后急剧扩增，并迅速分化为能够分泌多种细胞因子的次级效应细胞。我们的研究结果对柯萨奇病毒感染期间抗原交叉呈递的效率有影响。许多病毒（例如，像天花病毒和疱疹病毒这样的大型DNA病毒）编码几种蛋白质，其主要功能是对抗宿主的免疫反应，但这些蛋白质通常是徒劳的;一般来说，哺乳动物的免疫系统足以穿透病毒的盔甲，使受感染的动物能够产生免疫反应，从而根除或至少抑制传染性病原体。在这里，我们表明，柯萨奇病毒，一个小的RNA病毒，携带一个更强大的打击比其较大的DNA堂兄弟;它几乎完全逃避检测宿主CD 8 + T细胞，这通常是一个抗病毒免疫反应的关键组成部分之一。病毒是如何取得如此成功的？正常情况下，当病毒感染细胞时，某些宿主蛋白质会捕获病毒的小片段并将其展示在细胞表面，从而使它们能够被宿主免疫系统检测到-通常是通过称为CD 8 + T细胞的细胞。我们在这里表明，柯萨奇病毒非常有效地阻止这些“旗帜”以一种可以触发幼稚T细胞反应的形式到达细胞表面;实际上，病毒使细胞对CD 8 + T细胞“不可见”，创造了一个茧，病毒可以在其中繁殖，不受宿主免疫力的干扰。
Many viruses encode proteins whose major function is to evade or disable the host T cell response. Nevertheless, most viruses are readily detected by host T cells, and induce relatively strong T cell responses. Herein, we employ transgenic CD4+ and CD8+ T cells as sensors to evaluate in vitro and in vivo antigen presentation by coxsackievirus B3 (CVB3), and we show that this virus almost completely inhibits antigen presentation via the MHC class I pathway, thereby evading CD8+ T cell immunity. In contrast, the presentation of CVB3-encoded MHC class II epitopes is relatively unencumbered, and CVB3 induces in vivo CD4+ T cell responses that are, by several criteria, phenotypically normal. The cells display an effector phenotype and mature into multi-functional CVB3-specific memory CD4+ T cells that expand dramatically following challenge infection and rapidly differentiate into secondary effector cells capable of secreting multiple cytokines. Our findings have implications for the efficiency of antigen cross-presentation during coxsackievirus infection. Many viruses—for example, large DNA viruses like smallpox virus and herpesviruses—encode several proteins whose major function is to combat the host's immune response, but these proteins usually battle in vain; in general, the mammalian immune system is sufficiently accomplished to penetrate this viral armor, allowing the infected animal to mount an immune response that can eradicate—or, at least, suppress—the infectious agent. Here, we show that coxsackievirus, a small RNA virus, carries a far more powerful punch than its larger DNA cousins; it almost entirely evades detection by host CD8+ T cells, which usually are one of the key components of an antiviral immune response. How does the virus achieve such success? Normally, when a virus infects a cell, certain host proteins capture small fragments of the virus and display them on the cell's surface, allowing them to be detected by the host immune system—usually, by cells called CD8+ T cells. We show here that coxsackievirus very effectively prevents these “flags” from reaching the cell surface in a form that can trigger naïve T cells to respond; in effect, the virus renders the cell “invisible” to CD8+ T cells, creating a cocoon in which the virus can multiply undisturbed by host immunity.
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DOI：
10.1084/jem.20001021
发表时间：
2002-03-04
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Blattman JN;Antia R;Sourdive DJ;Wang X;Kaech SM;Murali-Krishna K;Altman JD;Ahmed R
通讯作者：
Ahmed R
影响因子：
5.4
作者：
Cornell, Christopher T.;Mosses, William B.;Whitton, J. Lindsay
通讯作者：
Whitton, J. Lindsay
影响因子：
30.5
作者：
Bedoui, Sammy;Whitney, Paul G.;Heath, William R.
通讯作者：
Heath, William R.
影响因子：
5.4
作者：
Knowlton, KU;Jeon, ES;Huber, S
通讯作者：
Huber, S
影响因子：
1.5
作者：
Halim, SS;Collins, DN;Ramsingh, AI
通讯作者：
Ramsingh, AI