Productive entry of foot-and-mouth disease virus via macropinocytosis independent of phosphatidylinositol 3-kinase
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)...
| Main Authors: | , , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
| Published: |
2018
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| Online Access: | https://hdl.handle.net/10356/87484 http://hdl.handle.net/10220/46731 |
| _version_ | 1811679370474946560 |
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| author | 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 |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences 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 |
| author_sort | Han, Shi-Chong |
| collection | NTU |
| description | 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. |
| first_indexed | 2024-10-01T03:08:05Z |
| format | Journal Article |
| id | ntu-10356/87484 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T03:08:05Z |
| publishDate | 2018 |
| record_format | dspace |
| spelling | ntu-10356/874842023-02-28T17:01:46Z Productive entry of foot-and-mouth disease virus via macropinocytosis independent of phosphatidylinositol 3-kinase 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 School of Biological Sciences Virus Replication DRNTU::Science::Biological sciences Foot-and-Mouth Disease Virus 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. Published version 2018-11-29T03:07:17Z 2019-12-06T16:42:53Z 2018-11-29T03:07:17Z 2019-12-06T16:42:53Z 2016 Journal Article 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 https://hdl.handle.net/10356/87484 http://hdl.handle.net/10220/46731 10.1038/srep19294 26757826 en Scientific Reports © 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 http://creativecommons.org/licenses/by/4.0/ 22 p. application/pdf |
| spellingShingle | Virus Replication DRNTU::Science::Biological sciences Foot-and-Mouth Disease Virus 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 Productive entry of foot-and-mouth disease virus via macropinocytosis independent of phosphatidylinositol 3-kinase |
| title | Productive entry of foot-and-mouth disease virus via macropinocytosis independent of phosphatidylinositol 3-kinase |
| title_full | Productive entry of foot-and-mouth disease virus via macropinocytosis independent of phosphatidylinositol 3-kinase |
| title_fullStr | Productive entry of foot-and-mouth disease virus via macropinocytosis independent of phosphatidylinositol 3-kinase |
| title_full_unstemmed | Productive entry of foot-and-mouth disease virus via macropinocytosis independent of phosphatidylinositol 3-kinase |
| title_short | Productive entry of foot-and-mouth disease virus via macropinocytosis independent of phosphatidylinositol 3-kinase |
| title_sort | productive entry of foot and mouth disease virus via macropinocytosis independent of phosphatidylinositol 3 kinase |
| topic | Virus Replication DRNTU::Science::Biological sciences Foot-and-Mouth Disease Virus |
| url | https://hdl.handle.net/10356/87484 http://hdl.handle.net/10220/46731 |
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