Abstract
The innate immune system features a web of interacting pathways that require exquisite regulation. To identify novel nodes in this immune landscape, we conducted a gain-of-function, genome-wide CRISPR activation screen with influenza A virus. We identified both appreciated and novel antiviral genes, including Jade family PHD zinc finger 3 (JADE3) a protein involved in directing the histone acetyltransferase histone acetyltransferase binding to ORC1 complex to modify chromatin and regulate transcription. JADE3 is both necessary and sufficient to restrict influenza A virus infection. Our results suggest a distinct function for JADE3 as expression of the closely related paralogs JADE1 and JADE2 does not confer resistance to influenza A virus infection. JADE3 is required for both constitutive and inducible expression of the well-characterized antiviral gene interferon-induced transmembrane protein 3 (IFITM3). Furthermore, we find JADE3 activates the NF-kB signaling pathway, which is required for the promotion of IFITM3 expression by JADE3. Therefore, we propose JADE3 activates an antiviral genetic program involving NF-kB–dependent IFITM3 expression to restrict influenza A virus infection.
Original language | English (US) |
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Article number | 107153 |
Journal | Journal of Biological Chemistry |
Volume | 300 |
Issue number | 4 |
DOIs | |
State | Published - Apr 2024 |
Keywords
- CRISPR/Cas9 screen
- IFITM3
- JADE
- NF-kB
- histone acetylation
- inflammation
- influenza A virus
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology