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IGF1R是呼吸道合胞病毒进入宿主的受体
2020-06-04 14:31

加拿大艾伯塔大学David J. Marchant小组的最新研究发现IGF1R是呼吸道合胞病毒(RSV)进入宿主的受体。这一研究成果于2020年6月3日在线发表在《自然》上。

研究人员揭示了RSV进入细胞的机制,其中细胞外的信号通过介导融合前RSV-F糖蛋白与胰岛素样生长因子1受体的结合,从而引发蛋白激酶C zeta(PKCζ)的激活。这种细胞信号级联反应将核仁素从细胞核招募到细胞质膜,在质膜上它与病毒的RSV-F结合。研究发现抑制PKCζ激活可防止气道类器官中核仁素向RSV颗粒的转运,并减少RSV感染小鼠的病毒复制和疾病发生。

这些发现揭示了一种病毒进入宿主的新机制,其中受体的参与和信号转导将共受体带到细胞表面的病毒颗粒,这可能有助于开发治疗RSV感染的新方法。

据悉,由感染引起的肺炎是人口死亡的主要原因之一。RSV引起的肺部感染严重威胁了人类健康,但几乎没有有效治疗手段。RSV靶点是气道中的纤毛上皮细胞,但尚不了解病毒(如RSV)是如何与这些细胞上的受体相互作用。核仁蛋白是RSV2的进入宿主的共受体,并且还介导流感、副流感病毒、某些肠病毒和引起图拉菌血症的细菌进入细胞。

附:英文原文

Title: IGF1R is an entry receptor for respiratory syncytial virus

Author: Cameron D. Griffiths, Leanne M. Bilawchuk, John E. McDonough, Kyla C. Jamieson, Farah Elawar, Yuchen Cen, Wenming Duan, Cindy Lin, Haeun Song, Jean-Laurent Casanova, Steven Ogg, Lionel Dylan Jensen, Bernard Thienpont, Anil Kumar, Tom C. Hobman, David Proud, Theo J. Moraes, David J. Marchant

Issue&Volume: 2020-06-03

Abstract: Pneumonia resulting from infection is one of the leading causes of death worldwide. Pulmonary infection by the respiratory syncytial virus (RSV) is a large burden on human health, for which there are few therapeutic options1. RSV targets ciliated epithelial cells in the airways, but how viruses such as RSV interact with receptors on these cells is not understood. Nucleolin is an entry coreceptor for RSV2 and also mediates the cellular entry of influenza, the parainfluenza virus, some enteroviruses and the bacterium that causes tularaemia3,4. Here we show a mechanism of RSV entry into cells in which outside-in signalling, involving binding of the prefusion RSV-F glycoprotein with the insulin-like growth factor-1 receptor, triggers the activation of protein kinase C zeta (PKCζ). This cellular signalling cascade recruits nucleolin from the nuclei of cells to the plasma membrane, where it also binds to RSV-F on virions. We find that inhibiting PKCζ activation prevents the trafficking of nucleolin to RSV particles on airway organoid cultures, and reduces viral replication and pathology in RSV-infected mice. These findings reveal a mechanism of virus entry in which receptor engagement and signal transduction bring the coreceptor to viral particles at the cell surface, and could form the basis of new therapeutics to treat RSV infection.

DOI: 10.1038/s41586-020-2369-7

Source: https://www.nature.com/articles/s41586-020-2369-7

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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