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Title: Productive entry of foot-and-mouth disease virus via macropinocytosis independent of phosphatidylinositol 3-kinase
Authors: Han, Shi-Chong
Guo, Hui-Chen
Sun, Shi-Qi
Jin, Ye
Wei, Yan-Quan
Feng, Xia
Yao, Xue-Ping
Cao, Sui-Zhong
Xiang Liu, Ding
Liu, Xiang-Tao
Keywords: Virus Replication
DRNTU::Science::Biological sciences
Foot-and-Mouth Disease Virus
Issue Date: 2016
Source: Han, S.-C., Guo, H.-C., Sun, S.-Q., Jin, Y., Wei, Y.-Q., Feng, X., . . . Liu, X.-T. (2016). Productive entry of foot-and-mouth disease virus via macropinocytosis independent of phosphatidylinositol 3-kinase. Scientific Reports, 6, 19294-. doi:10.1038/srep19294
Series/Report no.: Scientific Reports
Abstract: Virus entry is an attractive target for therapeutic intervention. Here, using a combination of electron microscopy, immunofluorescence assay, siRNA interference, specific pharmacological inhibitors, and dominant negative mutation, we demonstrated that the entry of foot-and-mouth disease virus (FMDV) triggered a substantial amount of plasma membrane ruffling. We also found that the internalization of FMDV induced a robust increase in fluid-phase uptake, and virions internalized within macropinosomes colocalized with phase uptake marker dextran. During this stage, the Rac1-Pak1 signaling pathway was activated. After specific inhibition on actin, Na+/H+ exchanger, receptor tyrosine kinase, Rac1, Pak1, myosin II, and protein kinase C, the entry and infection of FMDV significantly decreased. However, inhibition of phosphatidylinositol 3-kinase (PI3K) did not reduce FMDV internalization but increased the viral entry and infection to a certain extent, implying that FMDV entry did not require PI3K activity. Results showed that internalization of FMDV exhibited the main hallmarks of macropinocytosis. Moreover, intracellular trafficking of FMDV involves EEA1/Rab5-positive vesicles. The present study demonstrated macropinocytosis as another endocytic pathway apart from the clathrin-mediated pathway. The findings greatly expand our understanding of the molecular mechanisms of FMDV entry into cells, as well as provide potential insights into the entry mechanisms of other picornaviruses.
DOI: 10.1038/srep19294
Rights: © 2016 The Authors (Nature Publishing Group). This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit
Fulltext Permission: open
Fulltext Availability: With Fulltext
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