Inhibition of cell-free human T-cell leukemia virus type 1 infection at a postbinding step by the synthetic peptide derived from an ectodomain of thegp21 transmembrane glycoprotein

To investigate the roles of human T-cell leukemia virus type 1 (HTLV-1) env elope (Env) proteins gp46 and gp21 in the early steps of infection, the eff ects of the 23 synthetic peptides covering the entire Env proteins on trans mission of cell-free HTLV-1 were examined by PCR and by the plaque assay us ing a pseudotype of vesicular stomatis virus (VSV) bearing the Env of HTLV- 1 [VSV(HTLV-1)]. The synthetic peptide corresponding to amino acids 400 to 429 of the gp21 Env protein (gp21 peptide 400-429, Cys-Arg-Phe-Pro-Asn-Ile- Thr-Asn-Ser-His-Val-Pro-Ile-Leu-Gln-Glu-Arg-Pro-Pro-Leu-Glu-Asn-Arg-Val-Leu -Thr-Gly-Trp-Gly-Leu) strongly inhibited infection of cell-free HTLV-1. By using the mutant peptide, Asn407, Ser408, and Leu413, -419, -424, and -429 were confirmed to be important amino acids for neutralizing activity of the gp21 peptide 400-429. Addition of this peptide before or during adsorption of HTLV-1 at 4 degrees C did not affect its entry. However, HTLV-1 infecti on was inhibited about 60% when the gp21 peptide 400-429 was added even 30 min after adsorption of HTLV-1 to cells, indicating that the amino acid seq uence 400 to 429 on the gp21 Env protein plays an important role at the pos tbinding step of HTLV-1 infection. In contrast, a monoclonal antibody repor ted to recognize the gp46 191-196 peptide inhibited the infection of HTLV-1 at the binding step.