Choe Sunny S, Dodd Dana A, Kirkegaard Karla
Department of Microbiology and Immunology, Stanford University School of Medicine, CA 94305-5127, USA.
Virology. 2005 Jun 20;337(1):18-29. doi: 10.1016/j.virol.2005.03.036.
During poliovirus infection, anterograde traffic between the endoplasmic reticulum and the Golgi is inhibited due to the action of 3A, an 87 amino acid viral protein. The ability of poliovirus protein 3A to inhibit ER-to-Golgi traffic is not required for virus growth. Instead, we have suggested that the inhibition of host protein secretion, shown to reduce the secretion of interferon-beta, IL-6, and IL-8 and the expression of both newly synthesized MHC class I and TNF receptor in the plasma membrane of infected cells, affects growth in host organisms. To determine whether the ability of poliovirus 3A to inhibit ER-to-Golgi traffic is conserved, the ability of 3A proteins from several picornaviruses, including human rhinovirus 14, foot-and-mouth disease virus, enterovirus 71, hepatitis A, and Theiler's virus, was tested. Only the 3A proteins from another poliovirus, Sabin 3, and closely related coxsackievirus B3 inhibited ER-to-Golgi traffic as effectively as the 3A protein from poliovirus Mahoney type 1. Site-directed mutagenesis based on these findings and the three-dimensional structure of the amino-terminal domain of poliovirus 3A protein revealed that residues in the unstructured amino terminus of 3A are critical for the inhibition of host protein secretion.
在脊髓灰质炎病毒感染期间，由于87个氨基酸的病毒蛋白3A的作用，内质网和高尔基体之间的顺向运输受到抑制。脊髓灰质炎病毒蛋白3A抑制内质网到高尔基体运输的能力并非病毒生长所必需。相反，我们认为宿主蛋白分泌的抑制作用影响了病毒在宿主体内的生长，这种抑制作用表现为减少干扰素-β、白细胞介素-6和白细胞介素-8的分泌，以及感染细胞质膜上新合成的MHC I类分子和肿瘤坏死因子受体的表达。为了确定脊髓灰质炎病毒3A抑制内质网到高尔基体运输的能力是否保守，我们测试了几种小RNA病毒的3A蛋白的能力，包括人鼻病毒14型、口蹄疫病毒、肠道病毒71型、甲型肝炎病毒和泰勒氏病毒。只有另一种脊髓灰质炎病毒Sabin 3以及密切相关的柯萨奇病毒B3的3A蛋白，能像脊髓灰质炎病毒Mahoney 1型的3A蛋白一样有效地抑制内质网到高尔基体的运输。基于这些发现以及脊髓灰质炎病毒3A蛋白氨基末端结构域的三维结构进行的定点诱变表明，3A无结构氨基末端的残基对于抑制宿主蛋白分泌至关重要。
