Zebrafish hif1β attenuates antiviral innate immunity by suppressing Irf7 transcriptional activity

Abstract HIF1β, which serves as a common binding partner of the aryl hydrocarbon receptor and hypoxia-inducible factor (HIF)-α subunits, plays a key role in 2 cellular signaling pathways: the aryl hydrocarbon receptor and HIF pathways. Whether HIF1β is involved in antiviral innate immunity remains to be determined. In this study, we show that zebrafish hif1β is induced by viral infection. Overexpression of hif1β attenuates cellular antiviral responses. Further mechanistic assays indicate that zebrafish hif1β interacts with irf7 to repress irf7 transcriptional activity. Disruption of hif1β in zebrafish promotes survival following challenge with spring viremia of carp virus. Consistently, antiviral-responsive genes are significantly increased and spring viremia of carp virus replication is reduced in hif1β-null zebrafish. Thus, we uncover an expected role for hif1β in response to viral infection.