Thus, the substantial reduction of the IFNa response following concanamycin A treatment supports the notion that an endosomal receptor, such as TLR7 or TLR9, is involved in the initiation of the pDC response to rotavirus. Hence we predict that dsRNA derived from input virus is exposed following viral degradation, and not replication, as inactivated RRV, but neither genome-free TLPs nor VLPs, is sufficient for pDC activation/maturation and IFNa production. While it is possible that recognition of some combination of VP4, VP7 and dsRNA are required for IFNa induction, we instead believe that viral entry-mediated by VP7 and/or VP4-and subsequent recognition of genomic dsRNA or its degradation products are the critical components of this pathway.