title: Knockdown of synapse-associated protein Dlg1 reduces syncytium formation induced by human T-cell leukemia virus type 1.
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 (GLUT1DeltaC). GLUT1 expression in MDBK cells induced HTLV-1-mediated syncytium formation, and the activity was much greater than that of GLUT1DeltaC. 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.
authors.affiliation: Division of Virology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Niigata 951-8510, Japan.
authors.forename: Sakiko
authors.initials: S
authors.lastname: Yoshida
authors.forename: Masaya
authors.initials: M
authors.lastname: Higuchi
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Shoji
authors.forename: Manami
authors.initials: M
authors.lastname: Yoshita
authors.forename: Kojiro
authors.initials: K
authors.lastname: Ishioka
authors.forename: Masahiko
authors.initials: M
authors.lastname: Takahashi
authors.forename: Masayasu
authors.initials: M
authors.lastname: Oie
authors.forename: Yuetsu
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Makoto
authors.initials: M
authors.lastname: Uchiyama
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fujii
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D002450:Cell Communication; D002459:Cell Fusion; D002460:Cell Line; D000074288:Discs Large Homolog 1 Protein; D015870:Gene Expression; D015726:Giant Cells / Q000378:metabolism / Q000821:virology*; D051272:Glucose Transporter Type 1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015490:HTLV-I Infections / Q000378:metabolism / Q000503:physiopathology* / Q000821:virology; D015368:Human T-lymphotropic virus 1 / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D054731:PDZ Domains; D034622:RNA Interference; D011991:Receptors, Virus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D013601:T-Lymphocytes / Q000502:physiology* / Q000821:virology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C513314:DLG1 protein, human; D000074288:Discs Large Homolog 1 Protein; D051272:Glucose Transporter Type 1; D008565:Membrane Proteins; D011991:Receptors, Virus; C495677:SLC2A1 protein, human