Importantly, amino acid residues that are required for potent inhibitory activity of the HTLV-1 and BLV peptides are not fully resolved in the available HTLV-1 TM structure, yet this information is critical to the development of therapeutically relevant peptide or low-molecular-weight inhibitors of HTLV-1 entry [17, 22] . Moreover, other class I fusion proteins have extended non-helical elements in the C-terminal region of the trimer-of-hairpins and understanding how these elements contribute to the leash in a groove mechanism of fusion protein function will have broad relevance to anti-viral therapies [23, 24] . We therefore sought to examine the structure and function of the BLV TM and to compare this information with data derived from diverse class I fusion proteins and the related HTLV-1 TM structure.