Hysteresis in Hepatitis B Virus (HBV) Requires Assembly of Near-Perfect Capsids.
Hysteresis in Hepatitis B Virus (HBV) Requires Assembly of Near-Perfect Capsids.
复制标题
DOI：
10.1021/acs.biochem.1c00810
复制
发表时间：
2022-04-05
期刊：
影响因子：
2.9
通讯作者：
Zlotnick, Adam
中科院分区：
文献类型：
--
作者：
Starr, Caleb A.;Barnes, Lauren F.;Jarrold, Martin F.;Zlotnick, Adam
B型肝炎病毒（HBV）必须释放其内容物以启动感染，使得衣壳解体对病毒生命周期至关重要。衣壳组装通过弱相互作用的级联进行，以产生均匀的颗粒。然而，存在衣壳解离的滞后，其允许衣壳在它们不能组装的条件下持续存在。在这项研究中，我们试图通过检测尿素诱导的体外组装的HBV衣壳的解离来确定滞后的基础。通常，衣壳样品显示两个库的混合物，通过稳定性区分。不稳定衣壳解离对应于约5 μM的组装伪临界浓度（pcc），与组装反应中观察到的相同。稳定池的解离对应于亚飞摩尔PCC，指示滞后。组装反应中稳定衣壳的分数随着Cp制备的完整性而增加，并且当在更高的离子强度下进行缔合时，其改变Cp构象。当组装条件产生许多动力学捕获（不完整和过度生长）的产品时，不稳定的复合物更普遍。从稳定衣壳分离的Cp重组成稳定和不稳定衣壳的混合物。这些结果表明，滞后产生于一个理想的衣壳晶格，即使在该晶格中的一些取代基有缺陷。一致的结构研究表明，Cp二聚体和Cp衣壳之间的细微差异，我们提出，迟滞时出现HBV衣壳进行晶格依赖性的结构转变。
Hepatitis B Virus (HBV) must release its contents to initiate infection, making capsid disassembly critical to the viral life cycle. Capsid assembly proceeds through a cascade of weak interactions to yield uniform particles. However, there is a hysteresis to capsid dissociation that allows capsids to persist under conditions where they could not assemble. In this study we have sought to define the basis of hysteresis by examining urea induced dissociation of in vitro assembled HBV capsids. In general, capsid samples show a mixture of two pools, differentiated by stability. Labile capsid dissociation corresponds to a ~5 μM pseudo-critical concentration of assembly (pcc), the same as observed in assembly reactions. Dissociation of the stable pool corresponds to a sub-femtomolar pcc, indicative of hysteresis. The fraction of stable capsids in an assembly reaction increases with the integrity of the Cp preparation and when association is performed in higher ionic strength, which modifies Cp conformation. Labile complexes are more prevalent when assembly conditions yield many kinetically trapped (incomplete and overgrown) products. Cp isolated from stable capsids reassembles into a mixture of stable and labile capsids. These results suggest that hysteresis arises from an ideal capsid lattice, even when some of the substituents in that lattice have defects. Consistent with structural studies that show a subtle difference between Cp dimers and Cp in capsid, we propose that hysteresis arises when HBV capsids undergo a lattice-dependent structural transition.
登录
查看更多内容
影响因子：
7.7
作者：
Hadden JA;Perilla JR;Schlicksup CJ;Venkatakrishnan B;Zlotnick A;Schulten K
通讯作者：
Schulten K
影响因子：
5.6
作者：
Pierson EE;Keifer DZ;Kukreja AA;Wang JC;Zlotnick A;Jarrold MF
通讯作者：
Jarrold MF
DOI：
10.1021/acs.jpcb.6b02768
发表时间：
2016-07-07
期刊：
The journal of physical chemistry. B
影响因子：
--
作者：
Lazaro GR;Hagan MF
通讯作者：
Hagan MF
影响因子：
15
作者：
Pierson EE;Keifer DZ;Selzer L;Lee LS;Contino NC;Wang JC;Zlotnick A;Jarrold MF
通讯作者：
Jarrold MF
影响因子：
2.9
作者：
Ceres, P;Zlotnick, A
通讯作者：
Zlotnick, A