Abstract
Interferon (IFN) regulatory factors (IRF) are key transcrip- tion factors in cellular antiviral responses. IRF7, a virus- inducible IRF, expressed primarily in myeloid cells, is required for transcriptional induction of interferon α and antiviral genes. IRF7 is activated by virus-induced phosphory- lation in the cytoplasm, leading to its translocation to the nu- cleus for transcriptional activity. Here, we revealed a nontranscriptional activity of IRF7 contributing to its antiviral functions. IRF7 interacted with the pro-inflammatory tran- scription factor NF-κB-p65 and inhibited the induction of in- flammatory target genes. Using knockdown, knockout, and overexpression strategies, we demonstrated that IRF7 inhibited NF-κB–dependent inflammatory target genes, induced by virus infection or toll-like receptor stimulation. A mutant IRF7, defective in transcriptional activity, interacted with NF-κB-p65 and suppressed NF-κB–induced gene expression. A single- action IRF7 mutant, active in anti-inflammatory function, but defective in transcriptional activity, efficiently suppressed Sendai virus and murine hepatitis virus replication. We, therefore, uncovered an anti-inflammatory function for IRF7, independent of transcriptional activity, contributing to the antiviral response of IRF7.
Document Type
Article
Publication Date
2024
Digital Object Identifier (DOI)
https://doi.org/10.1016/j.jbc.2024.107200
Funding Information
This work was supported in part by the National Institutes of Health grants AI155545 (Sa. C.), AI165521 (Sa. C.), AA027456 (Sa. C.), and Medical Research Society (Sa. C.), and the University of Toledo College of Medicine and Life Sciences startup funds (Sa. C. and R. C.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Repository Citation
Fan, Shumin; Popli, Sonam; Chakravarty, Sukanya; Chakravarty, Ritu; and Chattopadhyay, Saurabh, "Non-transcriptional IRF7 interacts with NF-κB to inhibit viral inflammation" (2024). Markey Cancer Center Faculty Publications. 222.
https://uknowledge.uky.edu/markey_facpub/222
Notes/Citation Information
© 2024 THE AUTHORS. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).