Heat shock cognate protein 70 is a cell fusion-enhancing factor but not anentry factor for human T-cell lymphotropic virus type I

Heat shock cognate protein 70 (HSC70) has been shown to bind to the peptide corresponding to amino acids 197 to 216 of human T-cell lymphotropic virus type I (HTLV-I) envelope protein, gp46, and an anti-HSC70 monoclonal antib ody (mAb) inhibits HTLV-I-induced syncytium formation. These findings sugge st that HSC70 is necessary for the entry of HTLV-I into its target cells, H ere we showed that HSC70 directly binds to gp46 by co-immunoprecipitation o f HSC70 and gp46 from HTLV-I-producing human T-cell lysate. However, transd uction of human HSC70 cDNA into BaF3 cells, which were found to be highly r esistant to HTLV-I infection, did not support the HTLV-I entry, and HSC70 e xpressed in NIH3T3 cells, which were found to be almost resistant to syncyt ium formation upon cocultivation with HTLV-I-producing cells but sensitive to infection with cell-free HTLV-I, enhanced cell fusion induced by HTLV-I- producing cells, but did not enhance the entry of cell-free HTLV-I into the se cells, The mAb against HSC70 inhibited syncytium formation in NIH3T3 cel ls expressing HSC70, but showed little effect on infection of these cells w ith cell-free HTLV-I, These findings indicate that HSC70 markedly enhances syncytium formation induced by HTLV-I but does not facilitate HTLV-I entry into target cells. (C) 1999 Academic Press.