In order to investigate the role of interactions between XMRV Env and its receptor XPR1 in modulating membrane fusion and cell entry of XMRV, we created a soluble form of XMRV SU fused to the human IgG Fc fragment ( Fig. 2A) . The fusion protein was produced by transient transfection of 293T cells and purified using protein A beads using a procedure we had previously described for the JSRV SU fusion protein [43] . As shown in Figure 2B , incubation of XMRV SU-human IgG fusion protein with the permissive HTX cells resulted in an apparent fluorescence shift relative to that of secondary antibody alone (which served as a negative control), and overexpression of XPR1 receptor in HTX cells substantially increased the XMRV SU binding to the cells, indicating that the binding was specific. Similar results were also obtained in the permissive human 293, DU145, A549, dog MDCK, and monkey Vero cells (data not shown). The specific binding of XMRV SU for XPR1 was further confirmed in CHO/XPR1 cells which were established by transduction using a retroviral vector expressing XPR1; but surprisingly, we reproducibly detected a fluorescent shift in the parental CHO cells (Fig. 2B) , which are known to be nonpermissive for XMRV infection [37, 41] (also see Table 1 below).