The structure of the C-terminal segment of the BLV LHR and the accumulated data suggest a key role for the conserved arginine (Arg413) in the mechanism of envelope-mediated membrane fusion. Moreover, our recent data indicate that the equivalent arginine residue, Arg422, of the HTLV-1 LHR-mimetic peptide is critical to inhibitory activity [22] . Notably, for the HTLV-1 LHRbased inhibitor residues equivalent to Leu413, Arg416 and Leu419 are also of importance to the biological activity of the peptide [21, 22] . We therefore sought to establish whether or not the conserved arginine in the HTLV-1 LHR docks with the coiled coil in a similar manner to that of BLV and if this residue is important to membrane fusion mediated by the HTLV-1 TM. We generated a small panel of mutants in HTLV-1 envelope, substituting Arg416 of the LHR with alanine and lysine (R416A and R416K), and making similar substitutions for Arg422 (R422A and R422K). Using a monoclonal antibody recognising HTLV-1 SU, we confirmed by Western blotting and flow cytometry that all four mutant envelopes were expressed and post-translationally processed in a manner identical to wild type (Fig. 5A, B) . In syncytium formation assays, the individual alanine substitutions of Arg416 and Arg422 resulted in envelopes that are 91% and 97% less fusogenic than wild-type envelope respectively (Fig. 5C) . Significantly, the lysine substitution of Arg416 produced an envelope that was not significantly less fusogenic than wild type (P.0.05, t-test) (Fig. 5C ). However, Arg422 could not be functionally replaced with lysine, the R422K mutation resulted in an 88% reduction in fusogenic activity. Taken together with the data from the BLV R413K mutant, this suggests that HTLV-1 R422 adopts a near-identical conformation to BLV R413 at the Cterminal segment of the LHR.