TY - JOUR
T1 - Solid-to-fluid DNA transition inside HSV-1 capsid close to the temperature of infection
AU - Sae-Ueng, Udom
AU - Li, Dong
AU - Zuo, Xiaobing
AU - Huffman, Jamie B.
AU - Homa, Fred L.
AU - Rau, Donald
AU - Evilevitch, Alex
N1 - 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.).
PY - 2014/10/1
Y1 - 2014/10/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/84922061254
UR - https://www.scopus.com/pages/publications/84922061254#tab=citedBy
U2 - 10.1038/nchembio.1628
DO - 10.1038/nchembio.1628
M3 - Article
C2 - 25195012
AN - SCOPUS:84922061254
SN - 1552-4450
VL - 10
SP - 861
EP - 867
JO - Nature chemical biology
JF - Nature chemical biology
IS - 10
ER -