Trypsin-mediated cleavage of VP4 is canonically required for productive entry of rotavirus into permissive cells [33, 34, 35, 36] . However, it has previously been reported that murine bone marrow-derived DCs activate following exposure to uncleaved bovine rotavirus [40] , indicating that VP4 cleavage may be dispensable for the induction of the DC response. To investigate the role of trypsin-mediated cleavage of VP4 in both rotavirus infection of, and IFNa production by, human pDCs, we exposed pDCs to RRV grown in the absence of trypsin (non-trypsinized; NT-RRV). Although subsequent exposure to trypsin (thus cleaving VP4) increased infectivity of the uncleaved NT-RRV preparation 63-fold by plaque titration and intracellular NSP2 staining by 20fold in MA104s (data not shown), examination of NSP2 staining showed that similar proportions of pDCs were infected with either the cleaved or uncleaved NT-RRV preparations (p = 0.625; Wilcoxon signed rank test) ( Figure 6A-C) . Likewise, uncleaved NT-RRV induced IFNa production by a similar (p = 0.375; Wilcoxon signed rank test) percentage of pDCs, compared to cleaved NT-RRV ( Figure 6A , 6B and 6D). Thus, cleavage of VP4 by trypsin is dispensable for both pDC infection and IFNa induction by RRV.