Importantly, this finding may represent an alternative mechanism of IFNa induction in primary human pDCs. The ability of a pDC that takes up rotavirus to mount a vigorous type I IFN response independently of rotavirus mRNA or protein expression provides a potential mechanism by which the host could effectively circumvent the anti-IFN effects of NSP1-mediated IRF degradation [62] . At least three possible mechanisms exist for this phenotype: first, input or self nucleic acid released from necrotic or apoptotic cells may serve as PAMPs in neighboring cells, as has been previously described [64] . As RRV exposure, either to replicationcompetent or inactivated virus, does not induce substantial pDC death (Figure 1) , and as the cytokine response occurs rapidly following infection, this scenario seems unlikely. Secondly, input viral dsRNA may be exposed in the cytosol, the traditional cellular location for rotavirus replication, through the process of viral replication and interact with a cytosolic receptor such as RIG-I or protein kinase R (PKR). Rotavirus and reovirus, both members of the Reoviridae family, have been demonstrated to induce IFNb production in epithelial and human embryonic kidney 293T cells, respectively, via RIG-I, but not PKR or TLR3 [65, 66] . The mechanism by which input viral genomic RNA recognition might occur is unclear, however, as viral dsRNA is thought to remain encapsidated in the DLP and not be free in the cytoplasm during viral replication. Finally, rotavirus particles may be taken up by and degraded within the endosome, where dsRNA or its degradation products, including ssRNA fragments or a single strand of the dsRNA [12] , would be able to interact with TLR3, TLR7 or TLR9. As a biological role for known dsRNA receptors, such as RIG-I, PKR or TLR3, has not been demonstrated in human pDCs [2, 3, 4, 5, 6] , it is unlikely that these receptors are responsible for the observed IFNa induction in this system, although RIG-I like helicases have been recently implicated in the generation of a type I IFN response in pDCs from IFN receptor knockout mice [14] .