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.
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Change history
04 November 2014
In the version of this article initially published, a callout made to Figure 3a should have referred to Figure 4a in the first paragraph of the subsection entitled "Solid-to-fluid DNA transition inside the HSV-1 capsid" on page 864. The error has been corrected in the HTML and PDF versions of the article.
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Acknowledgements
We acknowledge T. Liu and I. Shefer for their substantial help with the manuscript preparation. We also thank B. Jönsson for discussions that have been inspiring for this work. We are grateful to G. Berry, M. Widom, P. LeDuc, M. Deserno and L. Walker for providing critically important feedback on data analysis. We acknowledge J. Shaw, B. Pittenger and M. Thompson from Bruker Nano Surfaces Division for outstanding support with AFM measurements. We thank A. Templeton for help with proofreading. The SAXS experiments were performed at beamline 12ID-B of the Advanced Photon Source at Argonne National Laboratory. We acknowledge the Advanced Photon Source, which is an Office of Science User Facility operated by Argonne National Laboratory for the US Department of Energy under contract no. DE-AC02-06CH11357. This work was supported by the Swedish Research Council, VR grant 622- 2008-726 (A.E.) and US National Science Foundation grant CHE-1152770 (A.E.). Support was also provided by the Public Health Service Grant AI060836 from the US National Institutes of Health (NIH) (F.L.H.) and by the McWilliams Fellowship in the Mellon College of Science (to U.S.). This work was partially supported by the Intramural Research Program of the National Institutes of Child Health and Human Development-NIH (to D.R.).
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U.S.-U. performed experiments, analyzed data and wrote the paper. D.L. performed experiments, analyzed data and provided analytical tools. X.Z. provided analytical tools and analyzed data. J.B.H. provided reagents and analyzed data. F.L.H. provided reagents and analyzed data. D.R. performed experiments, analyzed data and provided analytical tools. A.E. analyzed data, wrote the paper, provided analytical tools and provided reagents.
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Sae-Ueng, U., Li, D., Zuo, X. et al. Solid-to-fluid DNA transition inside HSV-1 capsid close to the temperature of infection. Nat Chem Biol 10, 861–867 (2014). https://doi.org/10.1038/nchembio.1628
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DOI: https://doi.org/10.1038/nchembio.1628
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