1. Extracellular vesicles derived from PPRV-infected cells enhance signaling lymphocyte activation molecular (SLAM) receptor expression and facilitate virus infection.
- Author
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Chen, Yan, Wang, Ting, Yang, Yang, Fang, Yuan, Zhao, Bao, Zeng, Wei, Lv, Daiyue, Zhang, Leyan, Zhang, Yanming, Xue, Qinghong, Chen, Xiwen, Wang, Jingyu, and Qi, Xuefeng
- Subjects
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EXTRACELLULAR vesicles , *VIRUS diseases , *LYMPHOCYTE transformation , *CELL communication , *ENDOCYTOSIS , *PESTE des petits ruminants , *ANIMAL populations - 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. Author summary: Peste des petitsruminants virus (PPRV) infection induces a transient but severe immunosuppression in the host, which threatens both small livestock and endangered susceptible wildlife populations in many countries. Despite extensive research, the mechanism underlying pathogenesis of PPRV infection remains elusive. Our data provide the first direct evidence that the EVs derived from PPRV-infected cells are involved in PPRV replication. In this study, the EVs derived from PPRV-infected goat PBMCs can enhance SLAM expression in the recipient cells, and more importantly, EVs-mediated increased SLAM expression enhances PPRV replication as well as the expression of various cytokines related to SLAM signaling pathway in the recipient cells. Taken together, our research has provided new insight into understanding the effect of EVs on PPRV replication and pathogenesis, and revealed a potential therapeutic target for antiviral intervention. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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