One important objective of this study was to understand the possible roles of the CT of XMRV Env in modulating membrane fusion and cell entry. We showed here that CT624 and CT613, which are truncated at or beyond the putative R peptide cleavage site of the XMRV Env (Fig. 3A) , induced apparent syncytia formation and cell-cell fusion in permissive 293 cells (Figs. 4 and 5), presumably due to the removal of the putative R peptide. Surprisingly, we observed apparent cell-cell fusion of CT624 and CT613 also in CHO cells (Fig. 6B) , which are known to be nonpermissive for XMRV infection, including these two truncation mutants (Table 1) . These results suggest two possibilities: first, CHO cells may express a low but functional level of XPR1 that permits cell-cell fusion of XMRV Env mutants and that the resistance of CHO cells to XMRV infection may be due to a block at the post-fusion steps. This possibility is supported in part by our observation that a soluble form of XMRV SU fusion protein reproducibly binds CHO cells relative to the negative control using secondary antibody alone (Fig. 2) . These binding results also argue against the possibility that potential N-linked glycosylation of XPR1 in CHO accounts for its resistance to XMRV infection, a situation that has been previously shown to be the case for several retroviruses [53, 54] . Second, the XPR1-mediated binding may The MLV titers were determined as described in Table 1 not be the sole trigger for XMRV Env-mediated membrane fusion. This scenario is in line with our finding that overexpression of XPR1 in 293 and CHO cells did not significantly increase the cell-cell fusion activities of XMRV Env truncation mutants despite their increased infection in these cells (Fig. 6B and Table 1 ; data not shown). We also considered the possibility that the XMRV Env truncation mutants may have acquired a receptor-independent, spontaneous cell-cell fusion or are pre-activated in 293T/ GFP cells due to their reduced kinetic barrier required for membrane fusion; however, the lack of infection in the CHO cells for the truncation mutants did not support this hypothesis ( Table 2) . Taken together, we favour the notion that, while XPR1 is a critical receptor for XMRV and is required for membrane fusion and cell entry, other cellular factors as yet to be identified are likely to be involved in cell entry and membrane fusion of XMRV. Consistent with this idea, it has been recently reported that XMRV does not infect BHK cells even when XPR1 is overexpressed in this cell line [47] , and that XMRV can infect A549 cells even though this cell line does not express a functional XPR1 receptor [55] . Hence, identification of additional cellular factors involved in XMRV entry would help to better understand the mechanisms of membrane fusion and cell entry mediated by XMRV Env.