In cell culture, the first step in infection is attachment to cellular receptors through interactions with the viral protein σ1 [4, 5] . σ1 interacts with two known receptors: sialic acid and junctional adhesion molecule 1 [6] [7] [8] . Following binding, virions are internalized by receptor-mediated endocytosis [9] . Endocytosis is an essential step in the viral life cycle under standard infection conditions [10] . Within the endosomal and/or lysosomal compartment, proteases convert virions into particles that resemble in vitro-generated intermediate subvirion particles (ISVPs) [10] [11] [12] [13] [14] . These uncoating intermediates, typically prepared using chymotrypsin or trypsin, lack σ3 and have a cleaved form of µ1. Studies using ISVPs and ISVPs recoated with recombinant outer capsid proteins reveal that σ3 plays a key role in regulating reovirus cell entry by interacting with, protecting, and controlling the conformational status of the underlying penetration protein µ1 [15] [16] [17] [18] . In cells that cannot efficiently mediate σ3 degradation during uncoating, reovirus infection is slow or blocked; these cells can be productively infected by particles that lack σ3 [2] . In vitro, ISVP-like particles can be generated by a variety of proteases in addition to chymotrypsin and trypsin, including proteinase K, thermolysin, endoproteinase lys-C, Cat L, Cat B and Cat S [3, [19] [20] [21] .