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Hokkaido University Collection of Scholarly and Academic Papers >
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Epstein-Barr virus exploits host endocytic machinery for cell-to-cell viral transmission rather than a virological synapse
| Title: | Epstein-Barr virus exploits host endocytic machinery for cell-to-cell viral transmission rather than a virological synapse |
| Other Titles: | Role of endocytic pathway in cell-to-cell EBV transmission |
| Authors: | Nanbo, Asuka Browse this author →KAKEN DB | | Kachi, Kunihiro Browse this author | | Yoshiyama, Hironori Browse this author →KAKEN DB | | Ohba, Yusuke Browse this author →KAKEN DB |
| Keywords: | Epstein-Barr virus | | cell-to-cell viral transmission | | adhesion molecule | | recycling endosome | | endocytosis |
| Issue Date: | Nov-2016 |
| Publisher: | Microbiology Society |
| Journal Title: | Journal of General Virology |
| Volume: | 97 |
| Issue: | 11 |
| Start Page: | 2989 |
| End Page: | 3006 |
| Publisher DOI: | 10.1099/jgv.0.000605 |
| PMID: | 27655016 |
| Abstract: | Epstein-Barr virus (EBV) establishes a lifelong latent infection in B lymphocytes and often is found in epithelial cells. Several lines of evidence indicate that viral transmission mediated by cell-to-cell contact is the dominant mode of infection by EBV for epithelial cells. However, its detailed molecular mechanism has not been fully elucidated. We investigated the role of host membrane trafficking machinery in this process. We have found that adhesion molecules critical for this process are expressed in EBV-positive and -negative Burkitt's lymphoma (BL) cells and multiple epithelial cell lines. Treatment with blocking antibodies against β1 and β2 integrin families and their ligands suppressed EBV transmission in a dose-dependent manner. We also confirmed that adhesion molecules are upregulated in co-cultured BL cells. Immunofluorescence staining revealed that the intracellular adhesion molecule 1 (ICAM-1) distributed to the cell surface and partially co-localized with recycling endosomes in co-cultured BL cells. Moreover, cell-to-cell EBV transmission was inhibited upon blocking endocytic recycling by expression of a dominant-negative form of a small GTPase Rab11 or by knockdown of Rab11, supporting the notion that the endocytic pathway-dependent trafficking of ICAM-1 to the cell surface of BL cells contributes to viral transmission by stabilizing cell-to-cell contact between the donor cells and recipient cells. Finally, we demonstrated that co-cultivation upregulated clathrin-mediated endocytosis in the recipient cells, allowing EBV to be internalized. Taken together, our findings demonstrate that EBV exploits host endocytic machinery in both donor and recipient cells, a process which is facilitated by cell-to-cell contact, thereby promoting successful viral transmission. |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/67567 |
| Appears in Collections: | 医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 南保 明日香
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