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- W2235199084 abstract "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." @default.
- W2235199084 created "2016-06-24" @default.
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- W2235199084 date "2016-01-13" @default.
- W2235199084 modified "2023-10-18" @default.
- W2235199084 title "Productive Entry of Foot-and-Mouth Disease Virus via Macropinocytosis Independent of Phosphatidylinositol 3-Kinase" @default.
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- W2235199084 doi "https://doi.org/10.1038/srep19294" @default.
- W2235199084 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4725844" @default.
- W2235199084 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/26757826" @default.
- W2235199084 hasPublicationYear "2016" @default.
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