Sagara Y, Inoue Y, Kojima E, Shiraki H, Maeda Y
Department of Research, Fukuoka Red Cross Blood Center, Fukuoka 818-8588, Japan.
AIDS Res Hum Retroviruses. 2000 Nov 1;16(16):1701-4. doi: 10.1089/08892220050193173.
In syncytium formation induced by HTLV-1-bearing cells, 71-kDa heat shock cognate protein (HSC70) functions as a receptor molecule and the receptor complex with beta-actin and palmitoyl(16:0)-oleoyl(18:1)-phosphatidylglycerol (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 segment corresponding to the region from Asp-197 to Leu-216 (gp46-197), and which serves as a binding site to both HSC70 and PG for syncytium formation, also had cytotoxic effects on target cell MOLT-4. This cytotoxicity was due to necrosis, not apoptosis. On the other hand, two other receptor-binding sites, Lys-111 to Asp-138 on gp46 (gp46-111) and Cys-400 to Leu-429 on gp21 (gp21-400), and which bound only with PG, had no cytotoxic effects on MOLT-4 cells. The HTLV-2 peptide (gp46-194; Glu194 to Leu-213) corresponding to the region of HTLV-1 gp46-197 showed no cytotoxicity, and interacted only with PG, not with either HSC70 or beta-actin. Amino acid alterations between HTLV-1 gp46-197 and HTLV-2 gp46-194 were significant on the hydrophilic face of the amphipathic structure. Taken together, the interaction between HSC70 and gp46 of HTLV-1 through the hydrophilic face of gp46-197 may lead to pore formation in lipid bilayers to be followed by membrane fusion or cell death.
在由携带HTLV-1的细胞诱导的合胞体形成过程中，71-kDa热休克同源蛋白（HSC70）作为受体分子发挥作用，进而形成了与β-肌动蛋白和棕榈酰（16:0）-油酰（18:1）-磷脂酰甘油（PG）的受体复合物。我们现在有证据表明，HTLV-1 gp46包膜蛋白与HSC70之间的分子缔合导致靶细胞膜表面形成孔道，随后细胞死亡。对应于Asp-197至Leu-216区域（gp46-197）的肽段，它作为合胞体形成时与HSC70和PG的结合位点，对靶细胞MOLT-4也具有细胞毒性作用。这种细胞毒性是由于坏死，而非凋亡。另一方面，gp46上的另外两个受体结合位点，即Lys-111至Asp-138（gp46-111）和gp21上的Cys-400至Leu-429（gp21-400），它们仅与PG结合，对MOLT-4细胞没有细胞毒性作用。与HTLV-1 gp46-197区域相对应的HTLV-2肽段（gp46-194；Glu194至Leu-21）没有细胞毒性，并且仅与PG相互作用，不与HSC70或β-肌动蛋白相互作用。HTLV-1 gp46-197和HTLV-2 gp46-194之间的氨基酸改变在两亲结构的亲水面上很显著。综上所述，HTLV-1的HSC70与gp46通过gp46-197的亲水面相互作用可能导致脂质双层中形成孔道，随后发生膜融合或细胞死亡。
