It is interesting to note that removal of a steric clash between R403 and the BLV coiled coil yields an envelope that is more fusogenic than wild type. For HTLV-1 an isoleucine, at a position equivalent to residue Arg403 in the BLV LHR, also appears to make a steric clash with the coiled coil and an alanine substitution of this residue in the context of an LHR-based peptide inhibitor yields a peptide with improved coiled coil-binding properties and increased inhibitory activity [21] . It is therefore clear that viral envelope has not evolved to optimise LHR binding to the coiled coil or to maximise fusogenicity. One plausible explanation is that membrane fusion needs to be kept in check. An overly fusogenic envelope may induce rampant membrane fusion and syncytium formation leading to cell death by apoptosis and thereby provide additional stimuli for a robust anti-viral immune response. Clearly, sub-optimal LHR/coiled-coil interactions have been maintained during viral evolution and suggest that the development of compounds that bind to the coiled coil with higher affinity than the LHR may be an achievable anti-viral strategy.