Phosphatidylglycerol Participates in Syncytium Formation Induced by HTLV Type 1-Bearing Cells

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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, β-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 β-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 β-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 β-actin, while there was no evidence of any interaction between PG and β-actin. These results suggest that HSC70 molecules on target cell surface interact with both PG in lipid bilayers and intracellular β-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.