We have shown earlier that S1P-mediated cleavage of GP-C is absolutely required for incorporation of the glycoprotein subunits into the virion envelope and thus for production of infectious LASV [23] . Therefore, we addressed the question of whether a S1P-specific a 1 -AT has the potential to prevent GP incorporation by blocking glycoprotein processing. To this end, a 1 -AT RRIL cells were infected in the presence or absence of doxycycline with either VSVDG/LASVGP or VSVwt as a control. At 24 h postinfection, viral particles released into the cell culture supernatant were purified over a 20% sucrose cushion and analyzed by means of immunoblotting. In viral particles from supernatants of noninduced a 1 -AT RRIL cells and CHO-K1 Tet-On control cells cleaved GP-2 was readily observed, whereas in the particulate material isolated from the supernatant of a 1 -AT RRIL expressing cells no glycoprotein was detected (Fig. 4A) . However, Western Blot analysis for VSV proteins revealed the release of these viral proteins into the supernatant of a 1 -AT RRIL expressing cells, which is consistent with our earlier findings that, in the absence of GP-C cleavage, enveloped non-infectious LASV-like particles containing the matrix protein Z and the ribonucleoprotein (RNP) complex, but devoid of viral glycoproteins, are still released [23] . The lower amount of VSV proteins observed in the cell lysate and supernatant of a 1 -AT RRIL expressing cells reflect lower levels of viral replication, which is due to less efficient virus spread (Fig. 4A) . In contrast to its ability to efficiently block incorporation of LASV GP into virions, the presence of a 1 -AT RRIL had no effect on the release of glycoprotein G containing wild-type VSV particles. The amount of VSV proteins detected in the supernatant from a 1 -AT RRIL expressing cells was similar to the amount of viral proteins observed in supernatants of non-induced cells and CHO-K1 cells, indicating efficient viral replication and cell-to-cell spread of VSVwt despite the presence of a 1 -AT RRIL (Fig. 4B) . Taken together, these data demonstrate that S1P-specific a 1 -antitrypsins have the potential to prevent LASV GP incorporation by inhibiting glycoprotein cleavage, which is an essential prerequisite for infectious progeny.