HTLV-1 interactions with primary CD4⁺ T cells and MDDCs are blocked by the HSPG-binding domain of VEGF₁₆₅. (A) Schematic representation of the interactions between VEGF_165, heparan sulfate chains, and NRP-1. (Left panel) The interactions between VEGF₁₆₅ exon 7 and heparan sulfate chains (dark blue arrow), between VEGF₁₆₅ exon 8 and the b domain of NRP-1 (light blue arrow), and between the b domain of NRP-1 and heparan sulfate chains (pink arrow). (Right diagram) The impact of these interactions on the formation of HSPG/NRP-1/VEGF₁₆₅ complexes and on NRP-1 dimerization. The subsequent recruitment of VEGF-R2 by VEGF₁₆₅ bound to HSPG/NRP-1 complexes is not depicted. (B) Effect of the VEGF₁₆₅ exon 7 peptide on HTLV-1entry into CD4⁺ T cells. Primary activated CD4⁺ T cells were incubated for 30 minutes with either a peptide homologous to a portion of VEGF₁₆₅ exon 7 or a control peptide of the same length and the levels of HTLV-1 SU binding (left histogram) or HTLV-1 virus internalization (right histogram) determined. The data are normalized to the control peptide (100%) and are the mean ± SD of 1 representative experiment of 2 performed. (C) Effects of HS lyase and exon 7 peptide on HTLV-1 entry into DCs. DCs were resuspended in HS lyase buffer and incubated in the presence or absence of HS lyase. The cells were then washed, incubated for 30 minutes with either the control peptide or VEGF₁₆₅ exon 7 peptide, and incubated with either culture medium (gray lines) or HTLV-1 virions (black lines), and the extent of HTLV-1 virus internalization was determined.