Israeli Hadar, Cohen-Dvashi Hadas, Shulman Anastasiya, Shimon Amir, Diskin Ron
Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel.
PLoS Pathog. 2017 Apr 27;13(4):e1006337. doi: 10.1371/journal.ppat.1006337. eCollection 2017 Apr.
Cell entry of many enveloped viruses occurs by engagement with cellular receptors, followed by internalization into endocytic compartments and pH-induced membrane fusion. A previously unnoticed step of receptor switching was found to be critical during cell entry of two devastating human pathogens: Ebola and Lassa viruses. Our recent studies revealed the functional role of receptor switching to LAMP1 for triggering membrane fusion by Lassa virus and showed the involvement of conserved histidines in this switching, suggesting that other viruses from this family may also switch to LAMP1. However, when we investigated viruses that are genetically close to Lassa virus, we discovered that they cannot bind LAMP1. A crystal structure of the receptor-binding module from Morogoro virus revealed structural differences that allowed mapping of the LAMP1 binding site to a unique set of Lassa residues not shared by other viruses in its family, illustrating a key difference in the cell-entry mechanism of Lassa virus that may contribute to its pathogenicity.
许多包膜病毒通过与细胞受体结合进入细胞，随后内化到内吞小室并通过pH诱导的膜融合。人们发现，在两种极具破坏力的人类病原体——埃博拉病毒和拉沙病毒进入细胞的过程中，一个先前未被注意到的受体转换步骤至关重要。我们最近的研究揭示了受体转换为LAMP1对拉沙病毒触发膜融合的功能作用，并表明保守组氨酸参与了这种转换，这表明该病毒家族的其他病毒也可能转换为LAMP1。然而，当我们研究与拉沙病毒基因相近的病毒时，发现它们无法结合LAMP1。莫罗戈罗病毒受体结合模块的晶体结构揭示了结构差异，这些差异使得LAMP1结合位点能够定位到该病毒家族其他病毒所不具有的一组独特的拉沙病毒残基上，这说明了拉沙病毒进入细胞机制中的一个关键差异，这可能与其致病性有关。
