The induction of both IFNa and TNFa by rotavirus may create a synergistic effect in the suppression of viral replication, as has been observed following RIG-I stimulus by myxoma virus [67] . Although the precise kinetics of induction are unclear, both TNFa and IFNa are also observed in pDC supernatants following influenza infection [24, 68, 69] . Interestingly, production of IFNa is delayed until 14-20 h following infection with a laboratory strain of H1N1 influenza, at which point ,4 ng/mL per million pDCs is detectable; this production was dependent on viral replication [69] . Conversely, we report that pDCs exposed to either live or inactivated rotavirus secrete approximately 10 ng/mL of IFNa by 6hpi. In agreement with previous findings [14] , the recognition of secreted IFNa is an important component of the amplification of the pDC IFNa response to both live and inactivated rotavirus. As such, the recognition of input viral genome and subsequent induction of an initial IFNa response prior to possible IRF7 inhibition allows for the establishment of an antiviral state by the global pDC population. While inactivated herpes simplex virus also induces IFNa, replication of vesicular stomatitis virus, Sendai virus and human respiratory syncytial virus has been demonstrated to be required for IFNa induction in pDCs [70, 71] . Together, this demonstration of rapid, potent, replication-independent induction of cytokine by a dsRNA virus, largely dependent on endosomal acidification, points to a novel mechanism leading to production of IFNa by human pDCs.