White Judith M, Whittaker Gary R
Department of Cell Biology, University of Virginia, Charlottesville, VA, USA.
Department of Microbiology & Immunology, Cornell University, Ithaca, NY, USA.
Traffic. 2016 Jun;17(6):593-614. doi: 10.1111/tra.12389. Epub 2016 Apr 7.
Ari Helenius launched the field of enveloped virus fusion in endosomes with a seminal paper in the Journal of Cell Biology in 1980. In the intervening years, a great deal has been learned about the structures and mechanisms of viral membrane fusion proteins as well as about the endosomes in which different enveloped viruses fuse and the endosomal cues that trigger fusion. We now recognize three classes of viral membrane fusion proteins based on structural criteria and four mechanisms of fusion triggering. After reviewing general features of viral membrane fusion proteins and viral fusion in endosomes, we delve into three characterized mechanisms for viral fusion triggering in endosomes: by low pH, by receptor binding plus low pH and by receptor binding plus the action of a protease. We end with a discussion of viruses that may employ novel endosomal fusion-triggering mechanisms. A key take-home message is that enveloped viruses that enter cells by fusing in endosomes traverse the endocytic pathway until they reach an endosome that has all of the environmental conditions (pH, proteases, ions, intracellular receptors and lipid composition) to (if needed) prime and (in all cases) trigger the fusion protein and to support membrane fusion.
阿里·海伦纽斯于1980年在《细胞生物学杂志》上发表了一篇具有开创性的论文，开启了包膜病毒在内体中融合领域的研究。在随后的这些年里，我们对病毒膜融合蛋白的结构和机制，以及不同包膜病毒融合所在的内体和触发融合的内体信号有了很多了解。基于结构标准，我们现在识别出三类病毒膜融合蛋白以及四种融合触发机制。在回顾了病毒膜融合蛋白和病毒在内体中融合的一般特征后，我们深入探讨了内体中病毒融合触发的三种已明确的机制：通过低pH值、通过受体结合加低pH值以及通过受体结合加蛋白酶的作用。我们最后讨论了可能采用新型内体融合触发机制的病毒。一个关键的要点是，通过在内体中融合进入细胞的包膜病毒会穿过内吞途径，直到它们到达一个具备所有环境条件（pH值、蛋白酶、离子、细胞内受体和脂质组成）的内体，这些条件能够（如有需要）使融合蛋白致敏并（在所有情况下）触发融合蛋白，以支持膜融合。
