Eukaryotic cells have evolved a myriad of ion channels, transporters, and pumps to maintain and regulate transmembrane ion gradients. As intracellular parasites, viruses also have evolved ion channel proteins, called viroporins, which disrupt normal ionic homeostasis to promote viral replication and pathogenesis. The first viral ion channel (influenza M2 protein) was confirmed only 23 years ago, and since then studies on M2 and many other viroporins have shown they serve critical functions in virus entry, replication, morphogenesis, and immune evasion. As new candidate viroporins and viroporin-mediated functions are being discovered, we review the experimental criteria for viroporin identification and characterization to facilitate consistency within this field of research. Then we review recent studies on how the few Ca(2+)-conducting viroporins exploit host signaling pathways, including store-operated Ca(2+) entry, autophagy, and inflammasome activation. These viroporin-induced aberrant Ca(2+) signals cause pathophysiological changes resulting in diarrhea, vomiting, and proinflammatory diseases, making both the viroporin and host Ca(2+) signaling pathways potential therapeutic targets for antiviral drugs.

中文翻译：

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钙传导性维罗帕林的病理生理后果。

真核细胞已经进化出无数的离子通道，转运蛋白和泵，以维持和调节跨膜离子梯度。作为细胞内的寄生虫，病毒还进化了离子通道蛋白，称为viroporins，可破坏正常的离子稳态，从而促进病毒复制和发病机理。仅在23年前就确认了第一个病毒离子通道（M2流感病毒），此后对M2和许多其他维罗帕林素的研究表明它们在病毒进入，复制，形态发生和免疫逃避中起关键作用。随着新的候选viroporin和viroporin介导的功能的发现，我们审查了viroporin鉴定和表征的实验标准，以促进该研究领域内的一致性。然后，我们回顾了最近的研究，有关如何进行少量Ca（2+）的viroporins利用宿主信号通路，包括存储操作的Ca（2+）进入，自噬和炎症小体激活。这些viroporin诱导的异常Ca（2+）信号引起病理生理变化，导致腹泻，呕吐和促炎性疾病，从而使viroporin和宿主Ca（2+）信号通路成为抗病毒药物的潜在治疗靶点。