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

Journal Article · Wed Oct 01 04:00:00 EDT 2014 · Nature Chemical Biology

DOI:https://doi.org/10.1038/NCHEMBIO.1628· OSTI ID:1241322

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

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.

• Research Organization: Argonne National Laboratory (ANL)
• Sponsoring Organization: Swedish Research Council; National Science Foundation (NSF); National Institutes of Health (NIH); USDOE Office of Science - Office of Basic Energy Sciences
• DOE Contract Number: AC02-06CH11357
• OSTI ID: 1241322
• Journal Information: Nature Chemical Biology, Journal Name: Nature Chemical Biology Journal Issue: 10 Vol. 10; ISSN 1552-4450
• Publisher: Nature Publishing Group
• Country of Publication: United States
• Language: English