Solid-to-fluid DNA transition inside HSV-1 capsid close to the temperature of infection

Udom Sae-Ueng, Dong Li, Xiaobing Zuo, Jamie B. Huffman, Fred L. Homa, Donald Rau, Alex Evilevitch

Research output: Contribution to journalArticle

Abstract

DNA in the human Herpes simplex virus type 1 (HSV-1) capsid is packaged to a tight density. This leads to tens of atmospheres of internal pressure responsible for the delivery of the herpes genome into the cell nucleus. In this study we show that, despite its liquid crystalline state inside the capsid, the DNA is fluid-like, which facilitates its ejection into the cell nucleus during infection. We found that the sliding friction between closely packaged DNA strands, caused by interstrand repulsive interactions, is reduced by the ionic environment of epithelial cells and neurons susceptible to herpes infection. However, variations in the ionic conditions corresponding to neuronal activity can restrict DNA mobility in the capsid, making it more solid-like. This can inhibit intranuclear DNA release and interfere with viral replication. In addition, the temperature of the human host (37 °C) induces a disordering transition of the encapsidated herpes genome, which reduces interstrand interactions and provides genome mobility required for infection.

Original languageEnglish (US)
Pages (from-to)861-867
Number of pages7
JournalNature chemical biology
Volume10
Issue number10
DOIs
StatePublished - Oct 1 2014

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Sae-Ueng, U., Li, D., Zuo, X., Huffman, J. B., Homa, F. L., Rau, D., & Evilevitch, A. (2014). Solid-to-fluid DNA transition inside HSV-1 capsid close to the temperature of infection. Nature chemical biology, 10(10), 861-867. https://doi.org/10.1038/nchembio.1628