NE, like many cellular proteases, is expressed as a proenzyme that becomes activated only after its pro-region is removed [54] . We envisioned two models by which NE could facilitate reovirus infection of U937 cells. In the first, NE could directly mediate σ3 degradation, leading to the generation of an ISVP-like particle. In the second, NE could act indirectly by activating another protease. To try to distinguish between these models, we examined the capacity of purified NE to directly mediate σ3 removal from Lang virions in vitro. Purified Lang virions were treated with NE for 1 and 4 h and the treated virus particles were analyzed by SDS-PAGE. As shown in Fig. 5A , NE efficiently removed σ3 from Lang virions; after 1 h very little intact σ3 remained on viral particles. After 4 h of NE treatment, σ3 was completely removed and the underlying µ1C was cleaved to the δ and φ fragments (φ was not retained on the gel). When we assayed the infectivity of the resultant particles by plaque assay we found that NE treatment did not negatively affect the titer of Lang particles (data not shown).