Exploring the Balance between DNA Pressure and Capsid Stability in Herpesviruses and Phages
Exploring the Balance between DNA Pressure and Capsid Stability in Herpesviruses and Phages
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DOI：
10.1128/jvi.01172-15
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发表时间：
2015-09-01
影响因子：
5.4
通讯作者：
Evilevitch, A.
中科院分区：
文献类型：
--
作者：
Bauer, D. W.;Li, D.;Evilevitch, A.
我们最近在疱疹病毒和噬菌体中发现，包装的病毒 DNA 会产生数十个大气压的压力，推动衣壳内部壁。我们首次使用差示扫描微量热法直接测量了衣壳中加压 DNA 释放的能量。此外，使用新的量热测定来准确确定诱导 DNA 释放的温度，我们发现内部 DNA 压力对病毒颗粒的稳定性有直接影响。我们发现，DNA 压力和衣壳强度之间的力平衡是各轮感染之间 DNA 保留所需的，在进化上多样化的细菌病毒（噬菌体 lambda 和 P22）以及真核病毒人类单纯疱疹 1 (HSV-1) 之间是保守的。我们的数据还表明，这些病毒的门静脉顶点是整个衣壳结构中最薄弱的点，也是病毒稳定性的致命弱点。这些病毒系统之间的比较表明，DNA堆积密度较高（导致衣壳压力较高）的病毒本质上具有更强的衣壳结构，可防止感染前基因组自发释放。这种力平衡对于病毒的生存和复制至关重要。研究破坏这种平衡的方法可能会导致新的抗突变抗病毒药物的开发。 重要性 病毒通常可以被描述为包含在保护性蛋白质外壳（称为衣壳）内的核酸基因组。对于许多双链 DNA 病毒，将大 DNA 分子限制在小蛋白质衣壳内会导致 DNA 处于高能状态，对衣壳内壁施加数十个大气压的压力。我们表明，病毒颗粒的稳定性（与感染性直接相关）受到包装基因组状态的强烈影响。使用细菌病毒（λ噬菌体）的扫描量热法作为实验模型系统，我们研究了与破坏病毒颗粒稳定性相关的基因组释放的热力学。此外，我们还比较了严格的基因组限制对不同细菌和真核病毒相对稳定性的影响。这些比较揭示了衣壳稳定性和包装基因组密度之间进化上保守的力平衡。
We have recently shown in both herpesviruses and phages that packaged viral DNA creates a pressure of tens of atmospheres pushing against the interior capsid wall. For the first time, using differential scanning microcalorimetry, we directly measured the energy powering the release of pressurized DNA from the capsid. Furthermore, using a new calorimetric assay to accurately determine the temperature inducing DNA release, we found a direct influence of internal DNA pressure on the stability of the viral particle. We show that the balance of forces between the DNA pressure and capsid strength, required for DNA retention between rounds of infection, is conserved between evolutionarily diverse bacterial viruses (phages lambda and P22), as well as a eukaryotic virus, human herpes simplex 1 (HSV-1). Our data also suggest that the portal vertex in these viruses is the weakest point in the overall capsid structure and presents the Achilles heel of the virus's stability. Comparison between these viral systems shows that viruses with higher DNA packing density (resulting in higher capsid pressure) have inherently stronger capsid structures, preventing spontaneous genome release prior to infection. This force balance is of key importance for viral survival and replication. Investigating the ways to disrupt this balance can lead to development of new mutation-resistant antivirals.IMPORTANCEA virus can generally be described as a nucleic acid genome contained within a protective protein shell, called the capsid. For many double-stranded DNA viruses, confinement of the large DNA molecule within the small protein capsid results in an energetically stressed DNA state exerting tens of atmospheres of pressures on the inner capsid wall. We show that stability of viral particles (which directly relates to infectivity) is strongly influenced by the state of the packaged genome. Using scanning calorimetry on a bacterial virus (phage lambda) as an experimental model system, we investigated the thermodynamics of genome release associated with destabilizing the viral particle. Furthermore, we compare the influence of tight genome confinement on the relative stability for diverse bacterial and eukaryotic viruses. These comparisons reveal an evolutionarily conserved force balance between the capsid stability and the density of the packaged genome.