SH pentamer transports K+

The small hydrophobic (SH) protein of respiratory syncytial virus (RSV) possesses viroporin properties, forming pentameric ion channels within lipid-raft structures in the Golgi membrane of infected cells (Gan SW et al. 2008, 2012; Triantafilou K et al. 2013; Li Y et al. 2014). The ion channel activity of viral SH results in imbalance of intracellular ions, thus contributing to the activation of NLRP3 inflammasome (Triantafilou K et al. 2013). RSV lacking SH fails to induce NLRP3-mediated caspase-1 activation and IL-1β secretion in human lung epithelial cells (Triantafilou K et al. 2013). Blocking the ion channel activity of SH with a small molecule called pyronin B reduces RSV virus production in monkey epithelial kidney Vero cells suggesting that targeting ion channel activity of SH could be a potential anti-RSV strategy (Li Y et al. 2014). Biochemical and spectroscopic analysis have shown that SH is a transmembrane protein with a single hydrophobic region spanning the membrane and a cytosolic tail at the carboxyl terminus (Carter Sd et al. 2010; Gan SW et al. 2012; Li Y et al. 2014). It is composed of α-helices in the transmembrane domains and a small α-helix at the C-terminus. SH has been shown to form a pentameric arrangement with a central pore in the transmembrane domain (Carter Sd et al. 2010; Gan SW et al. 2012; Li Y et al. 2014). Molecular modeling studies support the idea that SH functions as a viroporin forming pores that increase membrane permeability to ions and small molecules (Carter Sd et al. 2010; Li Y et al. 2014; Araujo GC et al. 2016). Besides inducing NLRP3 inflammasome formation, SH has been implicated in inhibiting apoptotic cell death potentially through its interaction with B cell associated protein 31 (BAP31) (Li Y et al. 2015). Both processes contribute to the pathogenesis of RSV.<p>This Reactome event shows RSV SH-mediated transport of potassium (K+) ions from the Golgi lumen to the cytosol.

呼吸道合胞病毒（RSV）的小疏水性（SH）蛋白具备病毒孔道特性，能够在感染细胞的内质网膜脂质筏结构中形成五聚体离子通道（Gan SW 等人，2008，2012；Triantafilou K 等人，2013；Li Y 等人，2014）。该病毒SH蛋白的离子通道活性导致细胞内离子失衡，从而促进NLRP3炎症小体的激活（Triantafilou K 等人，2013）。缺乏SH蛋白的RSV无法在人类肺上皮细胞中诱导由NLRP3介导的caspase-1激活和IL-1β分泌（Triantafilou K 等人，2013）。使用名为吡罗红的低分子量化合物阻断SH蛋白的离子通道活性可以降低猴上皮肾Vero细胞中RSV病毒的产生，这表明靶向SH蛋白的离子通道活性可能成为一种潜在的抗RSV策略（Li Y 等人，2014）。生化分析和光谱学分析表明，SH蛋白是一种跨膜蛋白，具有一个跨越膜的单个疏水区域和位于羧基末端的细胞质尾（Carter Sd 等人，2010；Gan SW 等人，2012；Li Y 等人，2014）。它由跨膜区域的α螺旋和一个位于C末端的较小α螺旋组成。SH蛋白已被证明形成一个具有跨膜域中央孔的五聚体结构（Carter Sd 等人，2010；Gan SW 等人，2012；Li Y 等人，2014）。分子建模研究表明，SH蛋白作为病毒孔道发挥作用，形成孔隙以增加膜对离子和小分子的通透性（Carter Sd 等人，2010；Li Y 等人，2014；Araujo GC 等人，2016）。除了诱导NLRP3炎症小体形成外，SH蛋白还与抑制细胞凋亡相关，这可能通过其与B细胞相关蛋白31（BAP31）的相互作用实现（Li Y 等人，2015）。这两个过程均与RSV的发病机制有关。《Reactome》事件展示了RSV SH介导的钾离子（K+）从高尔基腔到细胞质的运输。