ABSTRACT

Enterovirus 71 (EV71) is a non-enveloped virus and it can be released from host cells through a traditional cytolytic manner. Now, we showed EV71 could be spread non-lytically between cells during early viral infection. In order to explain this phenomenon, we separated supernatant fluids of rhabdomyosarcoma (RD) cells cultures infected with EV71 by isopycnic gradient centrifugation. Two populations of virus particles were morphology indistinguishable by transmission electron microscope (TEM). It showed that some EV71 particles were wrapped inside extracellular vesicles which were verified to be exosomes by immunoassay and morphologic analysis. In addition, exosomes containing viral RNA were shed in plasma of EV71-infected encephalitis in children. Our findings indicate that the “non-enveloped” EV71 virions could be wrapped within exosomes which promote their spread in the absence of cell lysis.

Abbreviation: EV71: enterovirus 71; EXO: exosome; RD: rhabdomyosarcoma; TEM: transmission electron microscope; HFMD: hand, foot, and mouth disease; HIV: immunodeficiency virus; HCV: hepatitis C virus; HTLV: Human T-cell lymphotropic virus; HAV: hepatitis A virus; MOI: multiplicity of infection; EVs: extracellular vesicles; VP1: viral capsid protein 1; NTA: nanoparticle tracking analysis; CNS: central nervous system

摘要

肠病毒71（EV71）是一种非包膜病毒，可以通过传统的细胞溶解方式从宿主细胞中释放。现在，我们显示了EV71可以在早期病毒感染过程中非裂解地在细胞之间传播。为了解释这种现象，我们通过等温梯度离心分离了感染了EV71的横纹肌肉瘤（RD）细胞培养物的上清液。通过透射电子显微镜（TEM）无法区分两个病毒颗粒的形态。结果表明，一些EV71颗粒包裹在细胞外囊泡中，通过免疫分析和形态学分析证实它们为外来体。另外，含有病毒RNA的外泌体在儿童被EV71感染的脑炎的血浆中脱落。

缩写：EV71：肠病毒71；EXO：外来体；RD：横纹肌肉瘤；TEM：透射电子显微镜；手足口病：手足口病；HIV：免疫缺陷病毒；HCV：丙型肝炎病毒；HTLV：人T细胞淋巴病毒；HAV：甲型肝炎病毒；MOI：感染复数；电动汽车：细胞外囊泡；VP1：病毒衣壳蛋白1；NTA：纳米颗粒跟踪分析；CNS：中枢神经系统