Lee Gi Young, Lee Sora, Lee Hye-Ra, Yoo Young Do
Laboratory of Molecular Cell Biology, Graduate School of Medicine, Korea University College of Medicine, Korea University, Seoul 02841, South Korea.
Laboratory of Molecular Cell Biology, Graduate School of Medicine, Korea University College of Medicine, Korea University, Seoul 02841, South Korea; Department of Biosystems and Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, South Korea.
Biochim Biophys Acta. 2016 Sep;1861(9 Pt A):1096-1101. doi: 10.1016/j.bbalip.2016.06.011. Epub 2016 Jun 17.
Viroporin p7 of the hepatitis C virus (HCV) acts as an ion channel for pH equilibration to stabilize HCV particles; most studies of p7 have focused on this role. However, pH equilibration by p7 via its ion channel activity does not fully explain the importance of p7 in HCV particle production. Indeed, several researchers have suggested p7 to have an unidentified ion channel-independent function. Here, we show that p7 has a novel role as a lipid raft adhesion factor, which is independent of its ion channel activity. We found that p7 targets not only the liquid-disordered (Ld) phase, but also the negatively-charged liquid-ordered (Lo) phase that can be represented as a lipid raft. p7 clusters at the phase boundary of the neutral Ld phase and the negatively-charged Lo phase. Interestingly, p7 targeting the Lo phase facilitates membrane-to-membrane adhesion, and this activity is not inhibited by p7 ion channel inhibitors. Our results demonstrated that HCV p7 has dual roles as a viroporin and as a lipid raft adhesion factor. This ion channel-independent function of p7 might be an attractive target for development of anti-HCV compounds.
丙型肝炎病毒（HCV）的病毒孔蛋白p7作为一种用于pH平衡的离子通道，以稳定HCV颗粒；大多数关于p7的研究都集中在这一作用上。然而，p7通过其离子通道活性进行的pH平衡并不能完全解释p7在HCV颗粒产生中的重要性。实际上，几位研究人员已表明p7具有一种未知的非离子通道依赖性功能。在此，我们表明p7具有作为脂筏粘附因子的新作用，这与其离子通道活性无关。我们发现p7不仅靶向液相无序（Ld）相，还靶向可代表脂筏的带负电荷的液相有序（Lo）相。p7聚集在中性Ld相和带负电荷的Lo相的相边界处。有趣的是，靶向Lo相的p7促进膜与膜的粘附，并且这种活性不受p7离子通道抑制剂的抑制。我们的结果表明，HCV p7具有作为病毒孔蛋白和脂筏粘附因子的双重作用。p7的这种非离子通道依赖性功能可能是开发抗HCV化合物的一个有吸引力的靶点。
