The Measles Virus Receptor SLAMF1 Can Mediate Particle Endocytosis.
The Measles Virus Receptor SLAMF1 Can Mediate Particle Endocytosis.
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DOI：
10.1128/jvi.02255-16
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发表时间：
2017-04-01
影响因子：
5.4
通讯作者：
Bailey D
中科院分区：
文献类型：
--
作者：
Gonçalves-Carneiro D;McKeating JA;Bailey D
信号淋巴细胞激活分子F1 （SLAMF1）是麻疹病毒（MeV）的微生物传感器和进入受体。在此，我们描述了SLAMF1介导MeV内吞作用的新作用，这与MeV基因组仅在细胞表面融合后才进入细胞的另一种普遍接受的模型形成了对比。我们证明，MeV作用于SLAMF1诱导了剧烈但短暂的形态变化，最显著的是膜泡的形成，这被证明与传入的病毒颗粒共定位，以及感染细胞中肌动蛋白细胞骨架的重排。MeV感染依赖于这些动态的细胞骨架变化以及通过巨噬细胞样途径的液体摄取，因为化学抑制这些过程会抑制进入。此外，我们确定了RhoA-ROCK-myosin II信号轴在MeV内化过程中的作用，强调了这一最近表征的途径在病毒进入过程中的新作用。我们的研究表明，MeV可以劫持通常参与细菌吞噬的微生物传感器，通过复杂的途径驱动内吞作用，该途径与典型的病毒巨噬作用、吞噬作用和机械转导具有共同的特征。这种摄取途径是slamf1阳性细胞所特有的，发生在病毒附着后60分钟内。麻疹病毒仍然是人类死亡的一个重要原因，这项研究为这一重要病原体感染的最初步骤提供了新的线索。麻疹是人类的一种重大疾病，自有记录以来，估计已造成2亿多人死亡。根据世界卫生组织目前的统计数字，每年仍有超过10万人死于疟疾，其中大多数是发展中国家的儿童。麻疹病毒是一种小包膜RNA病毒，在感染过程中感染广泛的细胞。特别是，免疫细胞通过在病毒表面发现的糖蛋白和免疫细胞受体SLAMF1之间的相互作用而被感染。在这项研究中，我们研究了麻疹病毒进入slamf1阳性细胞的步骤，并鉴定了病毒颗粒的内吞摄取。这项研究将影响我们对麻疹病毒相关免疫抑制的理解，以及麻疹病毒作为溶瘤治疗的应用。
The signaling lymphocyte activation molecule F1 (SLAMF1) is both a microbial sensor and entry receptor for measles virus (MeV). Herein, we describe a new role for SLAMF1 to mediate MeV endocytosis that is in contrast with the alternative, and generally accepted, model that MeV genome enters cells only after fusion at the cell surface. We demonstrated that MeV engagement of SLAMF1 induces dramatic but transient morphological changes, most prominently in the formation of membrane blebs, which were shown to colocalize with incoming viral particles, and rearrangement of the actin cytoskeleton in infected cells. MeV infection was dependent on these dynamic cytoskeletal changes as well as fluid uptake through a macropinocytosis-like pathway as chemical inhibition of these processes inhibited entry. Moreover, we identified a role for the RhoA-ROCK-myosin II signaling axis in this MeV internalization process, highlighting a novel role for this recently characterized pathway in virus entry. Our study shows that MeV can hijack a microbial sensor normally involved in bacterial phagocytosis to drive endocytosis using a complex pathway that shares features with canonical viral macropinocytosis, phagocytosis, and mechanotransduction. This uptake pathway is specific to SLAMF1-positive cells and occurs within 60 min of viral attachment. Measles virus remains a significant cause of mortality in human populations, and this research sheds new light on the very first steps of infection of this important pathogen. IMPORTANCE Measles is a significant disease in humans and is estimated to have killed over 200 million people since records began. According to current World Health Organization statistics, it still kills over 100,000 people a year, mostly children in the developing world. The causative agent, measles virus, is a small enveloped RNA virus that infects a broad range of cells during infection. In particular, immune cells are infected via interactions between glycoproteins found on the surface of the virus and SLAMF1, the immune cell receptor. In this study, we have investigated the steps governing entry of measles virus into SLAMF1-positive cells and identified endocytic uptake of viral particles. This research will impact our understanding of morbillivirus-related immunosuppression as well as the application of measles virus as an oncolytic therapeutic.