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 - Publisher Copyright:
© 2015 Nature America, Inc.
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.
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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 -