Inhibition of the secretory pathway by foot-and-mouth disease virus 2BC protein is reproduced by coexpression of 2B with 2C, and the site of inhibition is determined by the subcellular location of 2C
Inhibition of the secretory pathway by foot-and-mouth disease virus 2BC protein is reproduced by coexpression of 2B with 2C, and the site of inhibition is determined by the subcellular location of 2C
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DOI：
10.1128/jvi.00393-06
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发表时间：
2007-02-01
影响因子：
5.4
通讯作者：
Wileman, Thomas
中科院分区：
文献类型：
--
作者：
Moffat, Katy;Knox, Caroline;Wileman, Thomas
用小核糖核酸病毒感染细胞可导致蛋白质分泌的阻断。对于脊髓灰质炎病毒，这是通过3A蛋白实现的，并且随后促炎细胞因子的分泌和主要组织相容性复合物I类蛋白的表面表达的减少可抑制体内宿主免疫应答。口蹄疫病毒（FMDV）是另一种小核糖核酸病毒，可引起反刍动物的持续感染，这表明它也可能抑制免疫反应。内质网（ER）至高尔基体的蛋白质转运被FMDV 2BC蛋白质阻断。2BC在感染过程中被加工成213和2C，并且单个2B和2C蛋白不能阻断分泌，这一观察刺激我们研究2BC加工对分泌途径的影响。尽管2BC被快速加工成213和2C，但在FMDV感染的细胞中，蛋白质向质膜的转运仍然被阻断。阻断可以通过2B和2C的共表达来重建，表明2BC的加工不损害FMDV减缓分泌的能力。在此条件下，2C定位于高尔基体，并且在高尔基体中也发生了运输的阻断。有趣的是，当213与融合到ER保留元件的2C蛋白共表达时，转运中的阻断可以重定向到ER。因此，对于FMDV，分泌中的阻断依赖于2B和2C两者，后者决定阻断的位点。
Infection of cells with picornaviruses can lead to a block in protein secretion. For poliovirus this is achieved by the 3A protein, and the consequent reduction in secretion of proinflammatory cytokines and surface expression of major histocompatibility complex class I proteins may inhibit host immune responses in vivo. Foot-and-mouth disease virus (FMDV), another picornavirus, can cause persistent infection of ruminants, suggesting it too may inhibit immune responses. Endoplasmic reticulum (ER)-to-Golgi apparatus transport of proteins is blocked by the FMDV 2BC protein. The observation that 2BC is processed to 213 and 2C during infection and that individual 2B and 2C proteins are unable to block secretion stimulated us to study the effects of 2BC processing on the secretory pathway. Even though 2BC was processed rapidly to 213 and 2C, protein transport to the plasma membrane was still blocked in FMDV-infected cells. The block could be reconstituted by coexpression of 2B and 2C, showing that processing of 2BC did not compromise the ability of FMDV to slow secretion. Under these conditions, 2C was located to the Golgi apparatus, and the block in transport also occurred in the Golgi apparatus. Interestingly, the block in transport could be redirected to the ER when 213 was coexpressed with a 2C protein fused to an ER retention element. Thus, for FMDV a block in secretion is dependent on both 2B and 2C, with the latter determining the site of the block.