Nuclear receptors are
ligand-activated
transcription factors that play an important role in regulating innate
antiviral immunity and other biological processes. However, the role of
nuclear receptors in the host response to infectious bursal disease virus (IBDV)
infection remains elusive. In this study, we show that IBDV
infection or poly(I·C) treatment of DF-1 or HD11 cells markedly decreased
nuclear receptor subfamily 2 group F member 2 (NR2F2) expression. Surprisingly, knockdown, knockout, or inhibition of NR2F2 expression in host cells remarkably inhibited IBDV replication and promoted IBDV/poly(I·C)-induced
type I interferon and
interferon-stimulated genes expression. Furthermore, our data show that NR2F2 negatively regulates the
antiviral innate immune response by promoting the suppressor of
cytokine signaling 5 (SOCS5) expression. Thus, reduced NR2F2 expression in the host response to IBDV
infection inhibited viral replication by enhancing the expression of
type I interferon by targeting SOCS5. These findings reveal that NR2F2 plays a crucial role in
antiviral innate immunity, furthering our understanding of the mechanism underlying the host response to
viral infection. IMPORTANCE Infectious bursal disease (IBD) is an immunosuppressive disease causing considerable economic losses to the poultry industry worldwide.
Nuclear receptors play an important role in regulating innate
antiviral immunity. However, the role of
nuclear receptors in the host response to IBD virus (IBDV)
infection remains elusive. Here, we report that NR2F2 expression decreased in IBDV-infected cells, which consequently reduced SOCS5 expression, promoted
type I interferon expression, and suppressed IBDV
infection. Thus, NR2F2 serves as a negative factor in the host response to IBDV
infection by regulating SOCS5 expression, and intervention in the NR2F2-mediated host response by specific inhibitors might be employed as a strategy for prevention and treatment of IBD.