Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
J Biol Chem. 2011 May 20;286(20):17851-60. doi: 10.1074/jbc.M111.233965. Epub 2011 Apr 1.
The fusion (F) proteins of Newcastle disease virus (NDV) and Nipah virus (NiV) are both triggered by binding to receptors, mediated in both viruses by a second protein, the attachment protein. However, the hemagglutinin-neuraminidase (HN) attachment protein of NDV recognizes sialic acid receptors, whereas the NiV G attachment protein recognizes ephrinB2/B3 as receptors. Chimeric proteins composed of domains from the two attachment proteins have been evaluated for fusion-promoting activity with each F protein. Chimeras having NiV G-derived globular domains and NDV HN-derived stalks, transmembranes, and cytoplasmic tails are efficiently expressed, bind ephrinB2, and trigger NDV F to promote fusion in Vero cells. Thus, the NDV F protein can be triggered by binding to the NiV receptor, indicating that an aspect of the triggering cascade induced by the binding of HN to sialic acid is conserved in the binding of NiV G to ephrinB2. However, the fusion cascade for triggering NiV F by the G protein and that of triggering NDV F by the chimeras can be distinguished by differential exposure of a receptor-induced conformational epitope. The enhanced exposure of this epitope marks the triggering of NiV F by NiV G but not the triggering of NDV F by the chimeras. Thus, the triggering cascade for NiV G-F fusion may be more complex than that of NDV HN and F. This is consistent with the finding that reciprocal chimeras having NDV HN-derived heads and NiV G-derived stalks, transmembranes, and tails do not trigger either F protein for fusion, despite efficient cell surface expression and receptor binding.
新城疫病毒(NDV)和尼帕病毒(NiV)的融合(F)蛋白均通过与受体结合而被触发,这两种病毒都是通过第二种蛋白即附着蛋白来介导的。然而,NDV 的血凝素神经氨酸酶(HN)附着蛋白识别唾液酸受体,而 NiV 的 G 附着蛋白则识别 EphrinB2/B3 作为受体。已经评估了由两种附着蛋白的结构域组成的嵌合蛋白在与每种 F 蛋白的融合促进活性方面的作用。具有 NiV G 衍生的球形结构域和 NDV HN 衍生的茎、跨膜和细胞质尾巴的嵌合体能够有效地表达,结合 EphrinB2,并触发 NDV F 促进 Vero 细胞融合。因此,NDV F 蛋白可以通过与 NiV 受体结合而被触发,这表明由 HN 与唾液酸结合诱导的触发级联反应的一个方面在 NiV G 与 EphrinB2 结合中是保守的。然而,通过 G 蛋白触发 NiV F 的融合级联反应和通过嵌合体触发 NDV F 的融合级联反应可以通过受体诱导的构象表位的差异暴露来区分。该表位的增强暴露标志着 NiV G 触发 NiV F,但不是嵌合体触发 NDV F。因此,NiV G-F 融合的触发级联反应可能比 NDV HN 和 F 更复杂。这与以下发现一致,即具有 NDV HN 衍生的头部和 NiV G 衍生的茎、跨膜和尾巴的反向嵌合体不能触发任何 F 蛋白融合,尽管它们能够有效地在细胞表面表达和受体结合。