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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caveolins / metabolism
  • Clathrin / metabolism
  • Cytokines / metabolism
  • Extracellular Vesicles* / metabolism
  • Goats / genetics
  • Leukocytes, Mononuclear
  • Lymphocyte Activation
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Peste-des-Petits-Ruminants*
  • Peste-des-petits-ruminants virus* / genetics
  • Signaling Lymphocytic Activation Molecule Family Member 1 / metabolism
  • Virus Diseases*

Substances

  • Caveolins
  • Clathrin
  • Cytokines
  • MicroRNAs
  • Signaling Lymphocytic Activation Molecule Family Member 1

Grants and funding

XQ is supported by grants from The National Natural Science Foundation of China (Grant No.32172841, 31572588), Natural Science basic Research Program of Shaanxi Province (Grant No. 2021JM-102), and Agricultural Special Fund of Shaanxi Province (Grant No.XN17). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.