Zebrafish NF-kappaB/p65 Is Required for Antiviral Responses.

Transcriptional programs regulated by the NF-kappaB family are essential for the inflammatory response as well as for innate and adaptive immunity. NF-kappaB activation occurs via two major signaling pathways: the canonical and the noncanonical. The canonical NF-kappaB pathway responds to diverse immune stimulations and leads to rapid but transient activation. As a member of the canonical NF-kappaB family, p65 is thought to be a key regulator of viral infection. Because of the embryonic lethality of p65-null mice, the physiological role of p65 in the antiviral immune response is still unclear. In this study, we generated p65-null zebrafish, which were viable and indistinguishable from their wildtype (WT) siblings under normal conditions. However, p65-null zebrafish were more sensitive to spring viremia of carp virus infection than their WT siblings. Further assays indicated that proinflammatory and antiviral genes, including IFN, were downregulated in p65-null zebrafish after spring viremia of carp virus infection compared with their WT siblings. Our results thus suggested that p65 is required for the antiviral response, activating not only proinflammatory genes but also antiviral genes (including IFN).