State Key Laboratory of Veterinary Etiological Biology, National Foot-and-Mouth Disease Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agriculture Science, Lanzhou, 73004, China.
Vet Res. 2020 Jul 16;51(1):91. doi: 10.1186/s13567-020-00812-x.
Seneca Valley virus (SVV) is a non-encapsulated single-stranded positive-strand RNA virus whose transmission routes have not yet been fully elucidated. Exosomes have been implicated in the intercellular transport of a variety of materials, such as proteins, RNA, and liposomes. However, whether exosomes can mediate SVV intercellular transmission remains unknown. In this study, we extracted exosomes from SVV-infected IBRS-2 cells to investigate intercellular transmission. Our results suggest that the intercellular transmission of SVV is mediated by exosomes. The results of co-localization and RT-qPCR studies showed that exosomes harbor SVV and enable the virus to proliferate in both susceptible and non-susceptible cells. Furthermore, the replication of SVV was inhibited when IBRS-2 cells were treated with interfering RNA Rab27a and exosome inhibitor GW4869. Finally, neutralization experiments were performed to further verify whether the virus was encapsulated by the exosomes that mediated transmission between cells. It was found that exosome-mediated intercellular transmission was not blocked by SVV-specific neutralizing antibodies. This study reveals a new transmission route of SVV and provides clear evidence regarding the pathogenesis of SVV, information which can also be useful for identifying therapeutic interventions.
森那布病毒(SVV)是一种无囊膜的单链正链 RNA 病毒,其传播途径尚未完全阐明。外泌体参与多种物质(如蛋白质、RNA 和脂质体)的细胞间运输。然而,外泌体是否可以介导 SVV 的细胞间传播尚不清楚。在这项研究中,我们从 SVV 感染的 IBRS-2 细胞中提取外泌体,以研究细胞间的传播。我们的结果表明,SVV 的细胞间传播是由外泌体介导的。共定位和 RT-qPCR 研究的结果表明,外泌体携带 SVV 并使病毒在易感和非易感细胞中增殖。此外,当用干扰 RNA Rab27a 和外泌体抑制剂 GW4869 处理 IBRS-2 细胞时,SVV 的复制受到抑制。最后,进行了中和实验以进一步验证介导细胞间传播的外泌体是否包裹了病毒。结果发现,SVV 特异性中和抗体不能阻断外泌体介导的细胞间传播。本研究揭示了 SVV 的一种新的传播途径,并为 SVV 的发病机制提供了明确的证据,这些信息也有助于鉴定治疗干预措施。