Another surprising finding of this study is that CT609, which harbours the single arginine residue in the CT possesses a reduced fusogenicity relative to that of CT624 and CT613, which cannot be solely explained by its reduced surface expression (Figs. 4, 5, and 6). This observation is clearly different from what we had seen for JSRV Env [19] and is also somewhat different from some though not all of the previous studies on MoMLV [11, 44, 61] . Importantly, the tailless mutants, CT608 and CT606, are virtually fusion-defective (Fig. 4) , collectively leading us to propose that the N-terminal CT proximal to the MSD of XMRV Env is critical for Env-mediated membrane fusion. One possible mechanism is that residues in this region, including the highly conserved arginine present in many transmembrane proteins including the retroviral Envs, may interact with cell membrane and thus modulate lipid movement during the membrane fusion process [62, 63] .