Interaction of tSNARE syntaxin 18 with the papillomavirus minor capsid protein mediates infection
Interaction of tSNARE syntaxin 18 with the papillomavirus minor capsid protein mediates infection
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DOI：
10.1128/jvi.79.11.6723-6731.2005
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发表时间：
2005-06-01
影响因子：
5.4
通讯作者：
Meneses, PI
中科院分区：
文献类型：
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作者：
Bossis, L;Roden, RBS;Meneses, PI
乳头瘤病毒衣壳在感染过程中介导与细胞表面的结合以及病毒颗粒向核周区域的传递。为了更好地了解病毒如何在细胞中传播，我们试图鉴定与次要衣壳蛋白 L2 结合的细胞蛋白。我们已鉴定 Syntaxin 18 是一种与 1 型牛乳头瘤病毒 (BPV1) L2 相互作用的蛋白质。 Syntaxin 18 是一种位于内质网 (ER) 中的靶膜相关可溶性 N-乙基马来酰亚胺敏感因子附着蛋白受体 (tSNARE)。 FIAG 标记的突触蛋白 18 的异位表达会破坏 ER 运输，从而阻止 BPV1 假病毒体感染。此外，FLAG-syntaxin 18 的表达阻止了 BPV1 假病毒颗粒进入与 ER 一致的核周区域。遗传学研究发现了一个高度保守的 L2 结构域 DKILK，包含残基 40 至 44，在感染期间通过与 tSNARE 突触蛋白 18 相互作用介导 BPV1 通过 ER 运输。L2 的 DKILK 基序内的突变不会显着影响病毒粒子形态发生或在细胞表面的结合，从而阻止了 L2 与突触蛋白 18 的相互作用并破坏了 BPV1 感染。
The papillomavirus capsid mediates binding to the cell surface and passage of the virion to the perinuclear region during infection. To better understand how the virus traffics across the cell, we sought to identify cellular proteins that bind to the minor capsid protein L2. We have identified syntaxin 18 as a protein that interacts with bovine papillomavirus type 1 (BPV1) L2. Syntaxin 18 is a target membrane-associated soluble N-ethylmaleimide- sensitive factor-attachment protein receptor (tSNARE) that resides in the endoplasmic reticulum (ER). The ectopic expression of FIAG-tagged syntaxin 18, which disrupts ER trafficking, blocked BPV1 pseudovirion infection. Furthermore, the expression of FLAG-syntaxin 18 prevented the passage of BPV1 pseudovirions to the perinuclear region that is consistent with the ER. Genetic studies identified a highly conserved L2 domain, DKILK, comprising residues 40 to 44 that mediated BPV1 trafficking through the ER during infection via an interaction with the tSNARE syntaxin 18. Mutations within the DKILK motif of L2 that did not significantly impact virion morphogenesis or binding at the cell surface prevented the L2 interaction with syntaxin 18 and disrupted BPV1 infection.