细胞内货物受体 ERGIC-53 是产生传染性沙粒病毒、冠状病毒和丝状病毒颗粒所必需的。
The intracellular cargo receptor ERGIC-53 is required for the production of infectious arenavirus, coronavirus, and filovirus particles.
机构信息
Department of Medicine, Division of Immunobiology, University of Vermont, Burlington, VT 05405, USA; Cellular, Molecular and Biomedical Sciences Graduate Program, University of Vermont, Burlington, VT 05405, USA.
出版信息
Cell Host Microbe. 2013 Nov 13;14(5):522-34. doi: 10.1016/j.chom.2013.10.010.
Arenaviruses and hantaviruses cause severe human disease. Little is known regarding host proteins required for their propagation. We identified human proteins that interact with the glycoproteins (GPs) of a prototypic arenavirus and hantavirus and show that the lectin endoplasmic reticulum (ER)-Golgi intermediate compartment 53 kDa protein (ERGIC-53), a cargo receptor required for glycoprotein trafficking within the early exocytic pathway, associates with arenavirus, hantavirus, coronavirus, orthomyxovirus, and filovirus GPs. ERGIC-53 binds to arenavirus GPs through a lectin-independent mechanism, traffics to arenavirus budding sites, and is incorporated into virions. ERGIC-53 is required for arenavirus, coronavirus, and filovirus propagation; in its absence, GP-containing virus particles form but are noninfectious, due in part to their inability to attach to host cells. Thus, we have identified a class of pathogen-derived ERGIC-53 ligands, a lectin-independent basis for their association with ERGIC-53, and a role for ERGIC-53 in the propagation of several highly pathogenic RNA virus families.
沙粒病毒和汉坦病毒可引起严重的人类疾病。但人们对其增殖所需的宿主蛋白知之甚少。我们鉴定了与人源性亲合素相互作用的蛋白，这些蛋白可与典型沙粒病毒和汉坦病毒的糖蛋白（GPs）相互作用，研究表明，作为糖蛋白在早期胞吐途径中运输的载体蛋白，内质网-高尔基体中间腔 53kDa 蛋白（ERGIC-53）与沙粒病毒、汉坦病毒、冠状病毒、正粘病毒和丝状病毒的 GPs 结合。ERGIC-53 通过非依赖于凝集素的机制与沙粒病毒 GPs 结合，运输至沙粒病毒出芽部位，并整合入病毒粒子。ERGIC-53 是沙粒病毒、冠状病毒和丝状病毒增殖所必需的；在其缺失的情况下，含有 GP 的病毒颗粒形成但无感染性，部分原因是它们无法附着于宿主细胞。因此，我们鉴定了一类由病原体衍生的 ERGIC-53 配体，它们与 ERGIC-53 结合的非依赖于凝集素的基础，以及 ERGIC-53 在几种高致病性 RNA 病毒家族增殖中的作用。
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