Solid-to-fluid DNA transition inside HSV-1 capsid close to the temperature of infection.-猫眼课题宝

DOI：

10.1038/nchembio.1628

发表时间：

2014-10

期刊：

Nature chemical biology

影响因子：

14.8

通讯作者：

中科院分区：

生物学1区

文献类型：

作者：

Sae-Ueng U;Li D;Zuo X;Huffman JB;Homa FL;Rau D;Evilevitch A

来源链接：

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6528806/

人类单纯疱疹病毒1型(HSV-1)衣壳中的DNA被包装成紧密的密度。这导致了数十个大气压的内部压力，负责将疱疹基因组输送到细胞核中。在这项研究中，我们发现，尽管DNA在衣壳内处于液晶态，但它是液体状的，这有助于在感染期间将其喷射到细胞核中。我们发现，由链间排斥力引起的紧密包装的DNA链之间的滑动摩擦，会被易受疱疹感染的上皮细胞和神经元的离子环境所减少。然而，与神经元活动相对应的离子条件的变化可以限制衣壳中的DNA移动，使其更像固体。这会抑制核内DNA的释放，并干扰病毒复制。此外，人类宿主的温度(37℃)会导致被包裹的疱疹病毒基因组的无序转变，这减少了链间相互作用，并提供了感染所需的基因组迁移率。

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.