Viroporins
Viroporins
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DOI：
10.1007/978-3-319-20149-8_7
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发表时间：
2015-07-16
期刊：
影响因子：
--
通讯作者：
Hyser JM
中科院分区：
文献类型：
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作者：
Hyser JM
病毒编码的离子通道，称为病毒孔蛋白，由多种病毒表达，并且已经发现靶向几乎每个宿主细胞膜和隔室，包括内吞/外吞囊泡、ER、线粒体、高尔基体和质膜。病毒孔蛋白通常是非常小（<100个氨基酸）的整合膜蛋白，其共享共同的结构基序（邻近两亲性α-螺旋的碱性残基的保守簇），但在病毒之间仅具有有限的序列同源性。病毒孔蛋白的离子通道活性是复制所必需的，或者极大地增强复制和致病性。已经使用标准的电生理技术研究了通道特性，包括平面脂质双层、脂质体膜片钳或全细胞电压钳。一般来说，病毒孔蛋白是电压非依赖性非特异性单价阳离子通道，除了甲型流感病毒M2通道由于保守的HXXXW基序而形成高度特异性质子通道。病毒孔蛋白通道电流的范围在高度可变的（“突发样”）波动到良好分辨的单一（“方顶”）转换之间，并且新出现的数据表明通道活性的质量受到许多因素的影响，包括病毒孔蛋白合成/溶解、脂质环境和缓冲液的离子组成，以及病毒孔蛋白本身之间的内在差异。阻断病毒孔蛋白通道活性的化合物在体外和体内都是有效的抗病毒药物。令人惊讶的是，不同的病毒孔蛋白被相同的化合物抑制（例如，amantelatin和amiloride衍生物），尽管序列差异很大，但提高了靶向病毒孔蛋白的广泛作用的抗病毒药物的可能性。病毒孔蛋白的电生理学将继续在阐明病毒孔蛋白在发病机制中的功能作用和开发对抗病毒孔蛋白编码病原体的新药方面发挥关键作用。
Virus encoded ion channels, termed viroporins, are expressed by a diverse set of viruses and have been found to target nearly every host cell membrane and compartment, including endocytic/exocytic vesicles, ER, mitochondria, Golgi, and the plasma membrane. Viroporins are generally very small (<100 amino acids) integral membrane proteins that share common structure motifs (conserved cluster of basic residues adjacent to an amphipathic alpha-helix) but only limited sequence homology between viruses. Ion channel activity of viroporins is either required for replication or greatly enhances replication and pathogenesis. Channel characteristics have been investigated using standard electrophysiological techniques, including planar lipid bilayer, liposome patch clamp or whole-cell voltage clamp. In general, viroporins are voltage-independent non-specific monovalent cation channels, with the exception of the influenza A virus M2 channel that forms a highly specific proton channel due to a conserved HXXXW motif. Viroporin channel currents range between highly variable (‘burst-like’) fluctuations to well resolved unitary (‘square-top’) transitions, and emerging data indicates the quality of channel activity is influenced by many factors, including viroporin synthesis/solubilization, the lipid environment and the ionic composition of the buffers, as well as intrinsic differences between the viroporins themselves. Compounds that block viroporin channel activity are effective antiviral drugs both in vitro and in vivo. Surprisingly distinct viroporins are inhibited by the same compounds (e.g., amantadines and amiloride derivatives), despite wide sequence divergence, raising the possibility of broadly acting antiviral drugs that target viroporins. Electrophysiology of viroporins will continue to play a critical role in elucidating the functional roles viroporins play in pathogenesis and to develop new drugs to combat viroporin-encoding pathogens.