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源自 PPRV 感染细胞的细胞外囊泡增强信号淋巴细胞激活分子（SLAM）受体的表达，并促进病毒感染。

Extracellular vesicles derived from PPRV-infected cells enhance signaling lymphocyte activation molecular (SLAM) receptor expression and facilitate virus infection.

机构信息

College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China.

Shaanxi Animal Disease Control Center, Xi'an, China.

出版信息

PLoS Pathog. 2022 Sep 9;18(9):e1010759. doi: 10.1371/journal.ppat.1010759. eCollection 2022 Sep.

DOI:10.1371/journal.ppat.1010759
PMID:36084159
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9491601/
Abstract

Peste des petits ruminants virus (PPRV) is an important pathogen that seriously influences the productivity of small ruminants worldwide. PPRV is lymphotropic in nature and SLAM was identified as the primary receptor for PPRV and other Morbilliviruses. Many viruses have been demonstrated to engage extracellular vesicles (EVs) to facilitate their replication and pathogenesis. Here, we provide evidence that PPRV infection significantly induced the secretion levels of EVs from goat PBMC, and that PPRV-H protein carried in EVs can enhance SLAM receptor expression in the recipient cells via suppressing miR-218, a negative miRNA directly targeting SLAM gene. Importantly, EVs-mediated increased SLAM expression enhances PPRV infectivity as well as the expression of various cytokines related to SLAM signaling pathway in the recipient cells. Moreover, our data reveal that PPRV associate EVs rapidly entry into the recipient cells mainly through macropinocytosis pathway and cooperated with caveolin- and clathrin-mediated endocytosis. Taken together, our findings identify a new strategy by PPRV to enhance virus infection and escape innate immunity by engaging EVs pathway.

摘要

小反刍兽疫病毒（PPRV）是一种重要的病原体，严重影响了全球小反刍动物的生产力。PPRV 在性质上具有淋巴趋向性，SLAM 被确定为 PPRV 和其他副粘病毒的主要受体。许多病毒已被证明通过细胞外囊泡（EVs）来促进其复制和发病机制。在这里，我们提供的证据表明，PPRV 感染能显著诱导来自山羊 PBMC 的 EVs 的分泌水平，并且 EVs 中携带的 PPRV-H 蛋白可通过抑制 miR-218 来增强受体细胞中的 SLAM 表达，miR-218 是一种直接靶向 SLAM 基因的负 miRNA。重要的是，EVs 介导的 SLAM 表达增加增强了 PPRV 感染性以及受体细胞中与 SLAM 信号通路相关的各种细胞因子的表达。此外，我们的数据表明，PPRV 相关的 EVs 主要通过巨胞饮途径快速进入受体细胞，并与网格蛋白和小窝蛋白介导的内吞作用相配合。总之，我们的研究结果确定了 PPRV 通过利用 EVs 途径来增强病毒感染和逃避先天免疫的新策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c11e/9491601/674ffbf792f7/ppat.1010759.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c11e/9491601/22346f9a8ae8/ppat.1010759.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c11e/9491601/65afb6134086/ppat.1010759.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c11e/9491601/5a2fdeec9b6d/ppat.1010759.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c11e/9491601/13448b88bf17/ppat.1010759.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c11e/9491601/5d035a5f4fa0/ppat.1010759.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c11e/9491601/a2f49868e8a3/ppat.1010759.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c11e/9491601/5bb6b68ba5c8/ppat.1010759.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c11e/9491601/674ffbf792f7/ppat.1010759.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c11e/9491601/22346f9a8ae8/ppat.1010759.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c11e/9491601/65afb6134086/ppat.1010759.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c11e/9491601/5a2fdeec9b6d/ppat.1010759.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c11e/9491601/13448b88bf17/ppat.1010759.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c11e/9491601/5d035a5f4fa0/ppat.1010759.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c11e/9491601/a2f49868e8a3/ppat.1010759.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c11e/9491601/5bb6b68ba5c8/ppat.1010759.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c11e/9491601/674ffbf792f7/ppat.1010759.g008.jpg

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