We next assessed the effects of purified XMRV SU fusion protein on pseudoviral infection in HTX cells. Cells were pre- incubated with different amounts of XMRV SU fusion proteins for 1 h at 4uC, followed by switching the temperature to 37uC to initiate infection in the constant presence of the fusion protein for 6 h. As shown in Figure 2C , the XMRV SU fusion proteins substantially blocked the XMRV pseudoviral infection (p,0.05) in a dose-dependent manner, with the JSRV SU having no apparent effect (p.0.05). As would be expected, the JSRV SU fusion protein specifically blocked the JSRV pseudoviral infection but not that of XMRV (p,0.05) ( Fig. 2C and 2D ). The concentration of soluble XMRV SU required to block 50% of XMRV infection was ,10 ug/ml, which was relatively higher compared that of JSRV SU (,5 mg/ml, which is necessary to block 50% of JSRV infection) ( Fig. 2C and 2D ). Together, these results demonstrate that the soluble XMRV SU fusion protein interacts with the XPR1 receptor on the cell surface and functionally blocks the XMRV pseudoviral infection.