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 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.
Sagara
Y
Y
Department of Research, Fukuoka Red Cross Blood Center, Fukuoka 818-8588, Japan.
Inoue
Y
Y
Kojima
E
E
Shiraki
H
H
Maeda
Y
Y
D002460:Cell Line; D015686:Gene Products, env / Q000378:metabolism*; D015368:Human T-lymphotropic virus 1 / Q000472:pathogenicity*; D006801:Humans; D009336:Necrosis; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011991:Receptors, Virus / Q000378:metabolism*; D015682:Retroviridae Proteins, Oncogenic / Q000378:metabolism*; D013601:T-Lymphocytes / Q000473:pathology / Q000821:virology*; D014407:Tumor Cells, Cultured
D015686:Gene Products, env; C080823:HTLV-I receptor; D011956:Receptors, Cell Surface; D011991:Receptors, Virus; D015682:Retroviridae Proteins, Oncogenic; C055266:gp46 protein, Human T-cell leukemia virus type I