Herpes virus genome, the pressure is on.

Herpes virus genome, the pressure is on.
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DOI:
10.1021/ja404008r
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发表时间:
2013-07-31
影响因子:
15
通讯作者:
Evilevitch, Alex
Evilevitch, Alex
中科院分区:
化学1区
文献类型:
--
作者:
Bauer, David W.;Huffman, Jamie B.;Homa, Fred L.;Evilevitch, Alex

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单纯疱疹病毒1型(HSV-1)将其微米长的双链(DS)DNA基因组包装到一个纳米级的蛋白质壳中,称为衣壳。当被限制在衣壳内时,邻近的DNA链经历排斥的静电和水合力以及与包装DNA所需的紧曲率相关的弯曲应力。通过渗透抑制HSV-1衣壳的DNA释放,我们提供了第一个实验证据,表明由于受限的基因组,真核人类病毒内存在数十个大气压的高内压。此外,外部渗透压力的增加逐渐抑制了病毒的喷射,这表明内部压力能够推动整个基因组从病毒衣壳中喷射出来。尽管真核病毒和噬菌体经过了数十亿年的进化,但压力驱动的DNA喷射一直是保守的。这表明它是病毒感染的关键机制,从而为抗病毒治疗提供了一个新的靶点。
Herpes simplex virus type 1 (HSV-1) packages its microns-long double-stranded (ds) DNA genome into a nanometer-scale protein shell, termed the capsid. Upon confinement within the capsid, neighboring DNA strands experience repulsive electrostatic and hydration forces as well as bending stress associated with the tight curvature required of packaged DNA. By osmotically suppressing DNA release from HSV-1 capsids, we provide the first experimental evidence of a high internal pressure of tens of atmospheres within a eukaryotic human virus, resulting from the confined genome. Furthermore, the ejection is progressively suppressed by increasing external osmotic pressures, which reveals that internal pressure is capable of powering ejection of the entire genome from the viral capsid. Despite billions of years of evolution separating eukaryotic viruses and bacteriophages, pressure-driven DNA ejection has been conserved. This suggests it is a key mechanism for viral infection and thus presents a new target for antiviral therapies.
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