HTLV type 1 envelope glycoprotein gp46 evokes necrosis by binding to receptor complex

In syncytium formation induced by HTLV-1-bearing cells, 71-kDa heat shock c ognate protein (HSC70) functions as a receptor molecule and the receptor co mplex with beta -actin and palmitoyl(16:0)-oleoyl(18:1)-phosphatidylglycero l (PG) is thus formed. We now have evidence that the molecular association between HTLV-1 gp46 envelope protein and HSC70 led to pore formation on the surface of target cell membrane and cell death followed, The peptide segme nt corresponding to the region from Asp-197 to Leu-216 (gp46-197), and whic h serves as a binding site to both HSC70 and PG for syncytium formation, al so had cytotoxic effects on target cell MOLT-4. This cytotoxicity was due t o necrosis, not apoptosis, On the other hand, two other receptor-binding si tes, Lys-111 to Asp-138 on gp46 (gp46-111) and Cys-400 to Leu-429 on gp21 ( gp21-400), and which bound only with PC, had no cytotoxic effects on MOLT-4 cells, The HTLV-2 peptide (gp46-194; Glu-194 to Leu-213) corresponding to the region of HTLV-1 gp46-197 showed no cytotoxicity, and interacted only w ith PG, not with either HSC70 or beta -actin, Amino acid alterations betwee n HTLV-1 gp46-197 and HTLV-2 gp46-194 were significant on the hydrophilic f ace of the amphipathic structure. Taken together, the interaction between H SC70 and gp46 of HTLV-1 through the hydrophilic face of gp46-197 may lead t o pore formation in lipid bilayers to be followed by membrane fusion or cel l death.