Abstract
Human T-cell leukemia virus type 1 (HTLV-1) spreads through cell-to-cell contact by forming a virological synapse. Based on the finding that HTLV-1 envelope glycoprotein (Env) binds to a PDZ domain containing scaffold protein Dlg1, whose function has been implicated in the organization of neuronal and immunological synapses, we examined the role of Dlg1 in the cell-cell infection by HTLV-1. The coculture of an HTLV-1-infected T-cell line MT-2 with an uninfected MOLT-4 induced syncytium, a marker of cell-cell HTLV-1 infection, but an RNA interference-mediated knockdown of Dlg1 in both cells cooperatively reduced the syncytium formation. In HTLV-1-uninfected 293T cells, Dlg1 induced the clustering of GLUT1, a cellular receptor for HTLV-1, but such clustering was abrogated by a deletion of the PDZ domain binding motif of GLUT1 (GLUT1ΔC). GLUT1 expression in MDBK cells induced HTLV-1-mediated syncytium formation, and the activity was much greater than that of GLUT1ΔC. These results suggest that Dlg1, through the interaction with GLUT1 as well as Env, plays a positive role in the syncytium formation induced by HTLV-1.
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Acknowledgments
We thank Dr. Hiroyuki Miyoshi at RIKEN Tsukuba Institute, Dr. Tetsu Akiyama at University of Tokyo, Dr. Reuven Agami at the Netherlands Cancer Institute, and Dr. Hadi Al-Hasani at National Institutes of health for the CSII-EF-RfA plasmid, GFP-hDlg, pSUPER, and pCIS2-HA-GLUT1, respectively. We would like to express our gratitude to Chika Yamamoto and Misako Tobimatsu for their excellent technical assistance. This work was supported in part by a Grant-in-Aid for Scientific Research on Priority Areas and for Scientific Research (C) of Japan.
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Sakiko Yoshida and Masaya Higuchi have contributed equally to this study.
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Yoshida, S., Higuchi, M., Shoji, T. et al. Knockdown of synapse-associated protein Dlg1 reduces syncytium formation induced by human T-cell leukemia virus type 1. Virus Genes 37, 9–15 (2008). https://doi.org/10.1007/s11262-008-0234-0
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DOI: https://doi.org/10.1007/s11262-008-0234-0