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Updated: Nov 28, 2025

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Interrogating Host Antiviral Environments Driven by Nuclear DNA Sensing: A Multiomic Perspective.

Timothy R Howard1, Ileana M Cristea1

  • 1Department of Molecular Biology, Princeton University, Washington Road, Princeton, NJ 08544, USA.

Biomolecules
|December 1, 2020
PubMed
Summary

Nuclear DNA sensors detect foreign DNA in the nucleus, triggering antiviral responses. Proteomics studies reveal how these sensors interact and modify proteins to create an antiviral state.

Keywords:
DNA sensingIFI16cGASinnate immunitymass spectrometrypost-translational modificationsprotein interactionsproteomicstranscriptomicsvirus–host interactions

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Area of Science:

  • Immunology
  • Molecular Biology
  • Virology

Background:

  • Nuclear DNA sensors are key to the innate immune system, identifying pathogens like herpes simplex virus type 1 (HSV-1) and human cytomegalovirus (HCMV) within the cell nucleus.
  • These sensors bind to foreign DNA, initiating antiviral cytokine production and suppressing viral gene expression.
  • Host defense involves complex signaling pathways, including protein-protein interactions (PPIs) and post-translational modifications (PTMs), which remodel the cellular environment.

Purpose of the Study:

  • To review the role of proteomics in characterizing nuclear DNA sensors.
  • To highlight the discovery of functional PPIs and PTMs associated with DNA sensing.
  • To emphasize the importance of multiomic approaches for a systems-level understanding of DNA sensor function.

Main Methods:

  • Review of proteomics approaches applied to nuclear DNA sensor research.
  • Analysis of studies identifying protein-protein interactions (PPIs) and post-translational modifications (PTMs).
  • Examination of proteomic and secretomic changes induced by DNA sensing.

Main Results:

  • Proteomics has been instrumental in identifying functional PPIs and PTMs of nuclear DNA sensors.
  • Studies have characterized proteome and secretome alterations that establish an antiviral environment.
  • The review underscores the contribution of omics techniques to understanding DNA sensing mechanisms.

Conclusions:

  • Proteomics provides critical insights into the molecular mechanisms of nuclear DNA sensing.
  • Integrative multiomic strategies are essential for a comprehensive understanding of DNA sensors and their impact on host defenses.
  • Future research should focus on multiomic efforts to elucidate epigenetic and transcriptomic changes during viral infections.