Coxsackievirus B3 proteins directionally complement each other to downregulate surface major histocompatibility complex class I
Coxsackievirus B3 proteins directionally complement each other to downregulate surface major histocompatibility complex class I
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DOI：
10.1128/jvi.00198-07
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发表时间：
2007-07-01
影响因子：
5.4
通讯作者：
Whitton, J. Lindsay
中科院分区：
文献类型：
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作者：
Cornell, Christopher T.;Mosses, William B.;Whitton, J. Lindsay
小核糖核酸病毒携带少量具有多种功能的蛋白质，可以破坏和利用宿主细胞。我们之前已经证明三种柯萨奇病毒B3 （CVB3）蛋白（2B， 2BC和3A）靶向高尔基复合体并抑制蛋白转运。在这里，我们更详细地研究了这些影响，并评估了主要组织相容性复合体（MHC） I类分子的分布，这些分子是CD8(+) t细胞反应的关键介质。我们报道，在感染期间，伴随病毒蛋白合成，MHC I类表面表达迅速下调。然而，这种现象可能不仅仅是由于抑制逆行贩运；我们提出了一种新的机制，即CVB3 2B和2BC蛋白上调MHC I类（可能还有其他表面蛋白）的内在化，可能是通过聚焦高尔基复合体上的内吞囊泡。因此，我们的研究结果表明，CVB3携带至少三种方向互补的非结构蛋白；3A破坏高尔基复合体以抑制顺行运输，而2B和/或2BC上调内吞作用，迅速从细胞表面去除蛋白质。综上所述，这些作用可能使cvb3感染的细胞对CD8(+) T细胞不可见，并且许多抗病毒效应分子无法接触。这对CVB3的免疫逃避具有重要意义。
Picornaviruses carry a small number of proteins with diverse functions that subvert and exploit the host cell. We have previously shown that three coxsackievirus B3 (CVB3) proteins (2B, 2BC, and 3A) target the Golgi complex and inhibit protein transit. Here we investigate these effects in more detail and evaluate the distribution of major histocompatibility complex (MHC) class I molecules, which are critical mediators of the CD8(+) T-cell response. We report that concomitant with viral protein synthesis, MHC class I surface expression is rapidly downregulated during infection. However, this phenomenon may not result solely from inhibition of anterograde trafficking; we propose a new mechanism whereby the CVB3 2B and 2BC proteins upregulate the internalization of MHC class I (and possibly other surface proteins), perhaps by focusing of endocytic vesicles at the Golgi complex. Thus, our findings indicate that CVB3 carries at least three nonstructural proteins that directionally complement one another; 3A disrupts the Golgi complex to inhibit anterograde transport, while 2B and/or 2BC upregulates endocytosis, rapidly removing proteins from the cell surface. Taken together, these effects may render CVB3-infected cells invisible to CD8(+) T cells and untouchable by many antiviral effector molecules. This has important implications for immune evasion by CVB3.