Characterization of orange-spotted grouper (Epinephelus coioides) interferon regulatory factor 4 regulated by heat shock factor 1 during heat stress in response to antiviral immunity.

Interferon regulatory factor 4 (IRF4), in conjunction with thermogenic regulation, is a negative regulator of immune responses. Therefore, we examined whether temperature changes regulated the antiviral response of IRF4 in nervous necrosis virus (NNV)-infected orange-spotted groupers. We found that osgIRF4 mRNA expression was responsive to poly I:C stimulation and NNV infection. In vitro overexpression of osgIRF4 caused a marked decrease in the promoter activity of the antiviral protein Mx1, and magnified NNV replication. Notably, we showed that the IAD domain of osgIRF4 exerted a dominant inhibitory effect on the Mx1 promoter. Furthermore, on exposure to high temperatures, the action of osgIRF4 was dependent on heat shock factor 1 (HSF1) expression. Additionally, small interfering RNA knockdown of HSF1 abrogated high temperature-mediated osgIRF4 activity. These findings suggest that osgIRF4 is an essential negative regulator of innate antiviral immunity and enhances viral replication during heat stress in the orange-spotted grouper.