The “Histone Mimicry” by Pathogens
- 1Laboratory of Immune Cell Epigenetics and Signaling, The Rockefeller University, New York, New York 10065
- 2Laboratory of Methyltransferases in Development and Disease, Institute of Molecular and Cell Biology (IMCB), Singapore 138673
- 3Epinova DPU, Immuno-Inflammation Therapy Area, GlaxoSmithKline, Medicines Research Centre, Stevenage SG1 2NY, United Kingdom
- Correspondence: tarakho{at}mail.rockefeller.edu
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↵4 These authors contributed equally to this work.
Abstract
One of the defining characteristics of human and animal viruses is their ability to suppress host antiviral responses. Viruses express proteins that impair the detection of viral nucleic acids by host pattern-recognition receptors, block signaling pathways that lead to the synthesis of type I interferons and other cytokines, or prevent the activation of virus-induced genes. We have identified a novel mechanism of virus-mediated suppression of antiviral gene expression that relies on the presence of histone-like sequences (histone mimics) in viral proteins. We describe how viral histone mimics can interfere with key regulators of gene expression and contribute to the suppression of antiviral responses. We also describe how viral histone mimics can facilitate the identification of novel mechanisms of antiviral gene regulation and lead to the development of drugs that use histone mimicry for interference with gene expression during diseases.
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