通过细胞内模型探索乙型肝炎病毒感染动力学
Exploration of Hepatitis B Virus Infection Dynamics through an Intracellular Model
AI总结：
本研究构建了考虑HBV生命周期多步骤的细胞内感染动力学模型，通过数值求解与全局敏感性分析，明确HBx蛋白、衣壳再循环等对感染的关键影响，为HBV感染机制研究提供参考。
摘要：
细胞群体分析通常能提供宿主中病毒感染的平均信息，而细胞内模型则可捕捉单个细胞的应答反应。本研究的主要目标是全面分析乙型肝炎病毒（HBV）感染的细胞内动力学，并找出最具影响力的因素。本研究考虑了病毒生命周期中观测到的多个细胞内步骤，提出了一种HBV感染细胞内动力学模型。与实验数据对比后发现，该模型的解与实验结果吻合度良好。研究采用经典的四阶Runge-Kutta方法对所提模型进行数值求解，明确研究了HBx蛋白、含dslDNA的中间体、细胞内延迟以及cccDNA初始浓度的作用。为确定所提模型中正向敏感性最高和负向敏感性最高的参数，研究采用广泛使用的拉丁超立方抽样-偏秩相关系数法开展了全局敏感性分析。结果显示，HBx蛋白对感染动力学有显著影响，而细胞内延迟和含dslDNA的中间体对感染的影响并不显著。本研究还表明，亚病毒颗粒可能对感染的进展有潜在促进作用。此外，研究发现衣壳再循环（一种可能为HBV生命周期特有的细胞内过程，即新产生的部分衣壳返回细胞核并扩增cccDNA）在增强感染方面发挥着重要作用。
英文摘要：
Analysis of the cell population generally provides average information about viral infection in a host whereas the intracellular model captures the individual cellular responses. The primary goal of this study is to comprehensively analyze the intracellular dynamics of hepatitis B virus (HBV) infection and to identify the most influential factors. In this study, an intracellular HBV infection dynamics model is proposed by considering several intracellular steps that are observed in the virus life cycle. Upon comparison with the experimental data, it is seen that the model solutions exhibit a good agreement. The well-known fourth-order Runge-Kutta method is applied to numerically solve the proposed model. The effects of HBx proteins, dslDNA containing intermediates, intracellular delay and initial concentration of cccDNAs are explicitly studied. In order to identify the most positively and also the most negatively sensitive parameter of the proposed model, the global sensitivity analysis is performed using the widely-used method, Latin hypercube sampling-partial rank correlation coefficients. As a result, it is observed that HBx proteins have notable impacts on the dynamics of the infection, whereas intracellular delay and dslDNA-containing intermediates may not significantly affect the infection. This study also suggests that sub-viral particles could potentially contribute to the progression of the infection. Furthermore, recycling of capsids (an intracellular process perhaps unique to the HBV life cycle, where a portion of the newly produced capsids return to the nucleus and amplify the cccDNAs) is found to play an important role in enhancing the infection.
机构、总结、中文摘要均由AI分析而来，可能存在错误，请以论文正文为准。
