Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Trends Microbiol. 2009 Nov;17(11):514-21. doi: 10.1016/j.tim.2009.08.002. Epub 2009 Sep 30.
The alphaviruses and flaviviruses include many important human pathogens, such as the dengue, West Nile, and Chikungunya viruses. These enveloped viruses infect cells by a membrane fusion reaction triggered by the low pH in endosomes. Fusion is mediated by viral membrane proteins through their acid-dependent conversion from a dimer on the virus surface to a homotrimer inserted into the host cell membrane. Here we review recent studies on the regulatory mechanisms that silence these fusion proteins during virus exit and that sense low pH and mediate protein refolding during virus entry. We discuss results using truncated proteins to dissect the fusion reaction, and future research directions including the development of antiviral therapies against these medically important viruses.
甲病毒和黄病毒包括许多重要的人类病原体，如登革热、西尼罗河和基孔肯雅热病毒。这些包膜病毒通过内体中低 pH 值触发的膜融合反应感染细胞。融合是由病毒膜蛋白介导的，通过它们在酸性依赖性下从病毒表面上的二聚体转化为插入宿主细胞膜中的同源三聚体来实现。在这里，我们综述了最近关于调节机制的研究，这些机制在病毒释放时使融合蛋白沉默，并在病毒进入时感应低 pH 值并介导蛋白重折叠。我们讨论了使用截断蛋白来剖析融合反应的结果，以及包括开发针对这些医学上重要病毒的抗病毒疗法在内的未来研究方向。
