Retroviruses have been historically believed to fuse directly at the plasma membrane of target cells for entry and infection [42] . However, recent studies have shown that some retroviruses, including avian sarcoma leukosis virus (ASLV), mouse mammary tumor virus (MMTV), Jaagsiekte sheep retrovirus (JSRV), enzootic nasal tumor virus (ENTV), foamy virus, EIAV, and ecotropic Moloney MLV (MoMLV) require a low pH or low pH-dependent proteases for cell entry [13, 14, 15, 16, 17, 18, 19, 20, 21] . Here, we produced MoMLV pseudotypes bearing XMRV Env, and investigated the cell entry of XMRV by using classical chemical inhibitors that block pH-dependent viral entry [4] . We first treated human HTX cells (a subclone of HT1080) with a lysosomotropic agent, NH4Cl, and observed that it did not inhibit but rather somewhat enhanced XMRV infection (p.0.05). As expected, the infection of pH-dependent vesicular stomatitis virus (VSV) pseudovirions was dramatically decreased (p,0.01, Fig. 1A ). We next treated cells with a proton-pump inhibitor, Bafilomycin A1 (BafA1), and found interestingly that XMRV infection was again increased (p.0.05), yet that VSV entry was almost completely blocked by BafA1 even at the 5 nM concentration (p,0.01, Fig. 1B ). We noted that entry of 10A1 MLV was also slightly enhanced by BafA1 (p.0.05), but the effect was not dosedependent (Fig. 1B) . Similar effects of NH4Cl and BafA1 on XMRV entry were also observed in 293 and a human prostate cancer cell line, DU145 (data not shown), together supporting the idea that XMRV entry does not require a low pH as do the typical pH-dependent viruses, such as VSV and influenza A [4] .