Skip to main content

The functional interactome of PYHIN immune regulators reveals IFIX is a sensor of viral DNA.

Author(s): Diner, Benjamin A; Li, Tuo; Greco, Todd M; Crow, Marni S; Fuesler, John A; et al

To refer to this page use:
Abstract: The human PYHIN proteins, AIM2, IFI16, IFIX, and MNDA, are critical regulators of immune response, transcription, apoptosis, and cell cycle. However, their protein interactions and underlying mechanisms remain largely uncharacterized. Here, we provide the interaction network for all PYHIN proteins and define a function in sensing of viral DNA for the previously uncharacterized IFIX protein. By designing a cell-based inducible system and integrating microscopy, immunoaffinity capture, quantitative mass spectrometry, and bioinformatics, we identify over 300 PYHIN interactions reflective of diverse functions, including DNA damage response, transcription regulation, intracellular signaling, and antiviral response. In view of the IFIX interaction with antiviral factors, including nuclear PML bodies, we further characterize IFIX and demonstrate its function in restricting herpesvirus replication. We discover that IFIX detects viral DNA in both the nucleus and cytoplasm, binding foreign DNA via its HIN domain in a sequence-non-specific manner. Furthermore, IFIX contributes to the induction of interferon response. Our results highlight the value of integrative proteomics in deducing protein function and establish IFIX as an antiviral DNA sensor important for mounting immune responses.
Publication Date: 9-Feb-2015
Citation: Diner, Benjamin A, Li, Tuo, Greco, Todd M, Crow, Marni S, Fuesler, John A, Wang, Jennifer, Cristea, Ileana M. (2015). The functional interactome of PYHIN immune regulators reveals IFIX is a sensor of viral DNA.. Mol Syst Biol, 11 (1)
EISSN: 1744-4292
Language: eng
Type of Material: Journal Article
Journal/Proceeding Title: Mol Syst Biol
Version: Final published version. This is an open access article.

Items in OAR@Princeton are protected by copyright, with all rights reserved, unless otherwise indicated.