Density Analysis of Enterovirus D68 Shows Viral Particles Can Associate with Exosomes.
Density Analysis of Enterovirus D68 Shows Viral Particles Can Associate with Exosomes.
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DOI：
10.1128/spectrum.02452-21
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发表时间：
2022-02-23
影响因子：
3.7
通讯作者：
Tyler KL
中科院分区：
文献类型：
--
作者：
Rudy MJ;Coughlan C;Hixon AM;Clarke P;Tyler KL
肠道病毒D 68（EV-D 68）是一种引起呼吸道疾病的新病原体，与主要影响儿童的急性弛缓性肌炎有关。EV-D 68可以感染运动神经元，导致细胞死亡和运动控制的丧失，从而导致弛缓性麻痹。然而，病毒颗粒如何进入中枢神经系统（CNS）仍然是未知的。在这里，我们表明，三种不同密度的EV-D 68颗粒可以从感染的肌肉和神经细胞系（RD和SH-SY 5 Y）分离，使用高速密度离心分离细胞上清液。密度最低的峰由病毒颗粒组成，这些颗粒粘附在称为外泌体的小细胞外囊泡的外表面上。原型（历史）和当代EV-D 68菌株的分析表明，与外来体结合是EV-D 68的普遍特征。我们进一步表明，与外来体的相互作用增加了神经细胞系中的病毒感染性。对与外来体无关的两个较高密度峰的分析显示，在现代（2014）EV-D 68毒株中发现显著量的病毒滴度为1.20 g/cm 3，而该密度在原型Fermon毒株中具有非常低的病毒滴度。重要性尽管肠道病毒D 68（EV-D 68）和急性弛缓性肌病（AFM）之间存在很强的因果关系，但目前仍不清楚EV-D 68如何进入中枢神经系统以及哪些受体使其能够感染运动神经元。我们表明EV-D 68颗粒可以粘附于外泌体，将EV-D 68置于已知与细胞外囊泡相互作用的少数其他小核糖核酸病毒中。病毒污染的外泌体对允许细胞的摄取和感染将对EV-D 68受体的研究产生重大影响，并为病毒进入运动神经元提供可能的途径。这项工作确定了EV-D 68的一种新的细胞进入途径，并可能有助于确定AFM发展的遗传风险因素。
Enterovirus D68 (EV-D68) is an emerging pathogen which causes respiratory disease and is associated with an acute flaccid myelitis that predominately affects children. EV-D68 can infect motor neurons, causing cell death and a loss of motor control leading to flaccid paralysis. However, it remains unknown how viral particles gain entry into the central nervous system (CNS). Here, we show that three distinct densities of EV-D68 particle can be isolated from infected muscle and neural cell lines (RD and SH-SY5Y) using high-speed density centrifugation to separate cell supernatant. The lowest-density peak is composed of viral particles, which have adhered to the exterior surface of a small extracellular vesicle called an exosome. Analysis of prototypic (historic) and contemporary EV-D68 strains suggests that binding to exosomes is a ubiquitous characteristic of EV-D68. We further show that interaction with exosomes increases viral infectivity in a neural cell line. Analysis of the two higher-density peaks, which are not associated with exosomes, revealed that a significant amount of viral titer in the modern (2014) EV-D68 strains is found at 1.20 g/cm3, whereas this density has a very low viral titer in the prototypic Fermon strain. IMPORTANCE Despite the strong causal link between enterovirus D68 (EV-D68) and acute flaccid myelitis (AFM), it remains unclear how EV-D68 gains entry into the central nervous system and what receptors enable it to infect motor neurons. We show that EV-D68 particles can adhere to exosomes, placing EV-D68 among a handful of other picornaviruses which are known to interact with extracellular vesicles. Uptake and infection of permissive cells by virally contaminated exosomes would have major implications in the search for the EV-D68 receptor, as well as providing a possible route for viral entry into motor neurons. This work identifies a novel cellular entry route for EV-D68 and may facilitate the identification of genetic risk factors for development of AFM.
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影响因子：
64.8
作者：
Feng Z;Hensley L;McKnight KL;Hu F;Madden V;Ping L;Jeong SH;Walker C;Lanford RE;Lemon SM
通讯作者：
Lemon SM
DOI：
10.1073/pnas.1521230113
发表时间：
2016-02-23
影响因子：
11.1
作者：
Kowal, Joanna;Arras, Guillaume;Thery, Clotilde
通讯作者：
Thery, Clotilde
影响因子：
5.2
作者：
Cassidy H;Poelman R;Knoester M;Van Leer-Buter CC;Niesters HGM
通讯作者：
Niesters HGM
肠道病毒 D68 与两种单克隆抗体复合物的原子结构定义了不同的病毒中和机制
影响因子：
28.3
作者：
Zheng Q;Zhu R;Xu L;He M;Yan X;Liu D;Yin Z;Wu Y;Li Y;Yang L;Hou W;Li S;Li Z;Chen Z;Li Z;Yu H;Gu Y;Zhang J;Baker TS;Zhou ZH;Graham BS;Cheng T;Li S;Xia N
通讯作者：
Xia N
影响因子：
6.4
作者：
Melia, Charlotte E.;Peddie, Christopher J.;Barcena, Montserrat
通讯作者：
Barcena, Montserrat