The modest but reproducible enhancement of XMRV infection in the presence of NH4Cl and BafA1 could be explained by a block of viral particle degradation in the endosomes or lysosomes. To investigate this possibility and explore if XMRV entry requires cellular proteases, we performed pseudoviral infection in the presence or absence of leupeptin or cathepsin III inhibitor, both of which are broad spectra, lysosomal protease inhibitors. XMRV infection was enhanced by both protease inhibitors, albeit the increase was not statistically significant (p.0.05); however, infection of Ebola pseudovirions was dramatically impaired (p,0.01, Fig. 1C and 1D ). We noted that VSV infection was also slightly enhanced by these two protease inhibitors but the effect was not dose-dependent. The effect of these protease inhibitors on Ebola infection was consistent with the notion that Ebola GP-mediated membrane fusion with endosome requires cellular cathepsin B and L [22, 26] . Taken together, these results show that XMRV entry does not require a low pH or low pHdependent cellular proteases, and that endocytosis XMRV may occur for XMRV but this would likely result in virions inactivation through pH-dependent host proteases.