title: Phosphatidylglycerol participates in syncytium formation induced by HTLV type 1-bearing cells.
abstract: We previously reported that 71-kDa heat shock cognate protein (HSC70) was expressed on the cell surface of human T cell lymphotropic virus type 1 (HTLV-1)-susceptible cells and that HSC70, beta-actin, and a lipid-like component on the target cell membrane participated in syncytium formation by HTLV-1. We have now identified this lipid-like component to be palmitoyl (16:0)-oleoyl (18:1)-phosphatidylglycerol (POPG), using preparative thin-layer chromatographic fractionation and tandem mass spectrometric analysis. In the syncytium formation assay, exogenously added PG inhibited cell-to-cell transmission of HTLV-1 in a dose-dependent manner. Other phospholipids showed less (PE) or no effect (PC, PS, PI, PA, lysoPC, lysoPE, and CL). Binding experiments showed that PG interacted with three synthetic peptides, gp46--111, gp46--197, and gp21--400, which correspond to regions Lys111--Asp138 and Asp197--Leu216 on the gp46 surface glycoprotein, and to region Cys400--Leu429 on the gp21 transmembrane glycoprotein, respectively, as well as with intact gp46 and gp21 proteins of HTLV-1. On the other hand, HSC70 and beta-actin interacted with gp46--197 and gp46, not with gp46--111. However, the eluate from an affinity column coupled with gp46--111 contained not only PG but also HSC70 and beta-actin, despite the lack of direct interaction between gp46--111 and these proteins. In the in vitro binding assay, HSC70 showed interaction with both PG and beta-actin, while there was no evidence of any interaction between PG and beta-actin. These results suggest that HSC70 molecules on target cell surface interact with both PG in lipid bilayers and intracellular beta-actin and that these three cellular components form a receptor complex that plays a critical role in syncytium formation induced by HTLV-1-bearing cells.
authors.affiliation: Department of Research, Fukuoka Red Cross Blood Center, Fukuoka 818-8588, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Sagara
authors.forename: Y
authors.initials: Y
authors.lastname: Inoue
authors.forename: E
authors.initials: E
authors.lastname: Kojima
authors.forename: C
authors.initials: C
authors.lastname: Ishida
authors.forename: H
authors.initials: H
authors.lastname: Shiraki
authors.forename: Y
authors.initials: Y
authors.lastname: Maeda
mesh_terms: D000199:Actins / Q000378:metabolism; D002460:Cell Line; D002855:Chromatography, Thin Layer; D004305:Dose-Response Relationship, Drug; D015686:Gene Products, env / Q000378:metabolism; D015726:Giant Cells / Q000502:physiology*; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D015368:Human T-lymphotropic virus 1 / Q000187:drug effects / Q000378:metabolism / Q000472:pathogenicity*; D006801:Humans; D013058:Mass Spectrometry; D010715:Phosphatidylglycerols / Q000494:pharmacology / Q000502:physiology*; D011485:Protein Binding; D011991:Receptors, Virus / Q000378:metabolism; D015682:Retroviridae Proteins, Oncogenic / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000473:pathology* / Q000821:virology*; D054299:env Gene Products, Human Immunodeficiency Virus
chemical_list: D000199:Actins; D015686:Gene Products, env; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C494371:HSPA8 protein, human; D010715:Phosphatidylglycerols; D011991:Receptors, Virus; D015682:Retroviridae Proteins, Oncogenic; D054299:env Gene Products, Human Immunodeficiency Virus; C055265:gp21 protein, Human T-lymphotropic virus 1; C055266:gp46 protein, Human T-cell leukemia virus type I