通过肝细胞增殖与衣壳再循环理解乙型肝炎病毒感染
Understanding Hepatitis B Virus Infection through Hepatocyte Proliferation and Capsid Recycling
AI总结：
本文构建两个整合肝细胞增殖与衣壳再循环的HBV生物数学模型，并用黑猩猩数据校准，揭示急慢性感染及不同增殖模式下的清除与加重机制。
摘要：
未感染和已感染肝细胞的增殖，以及含DNA衣壳的再循环，是在乙型肝炎病毒（HBV）感染清除中发挥重要作用的两大机制。本研究通过两个同时考虑肝细胞增殖和衣壳再循环的计算机生物数学模型，考察该感染的时间动态。两个模型均基于现有文献中的一项关键发现构建：受感染细胞的有丝分裂产生两个未感染子代细胞。在第一个模型中，我们考察规则增殖（持续发生），而第二个模型处理不规则增殖（当肝细胞总数降至其初始容量的70%以下时发生）。模型利用从一只成年黑猩猩获得的实验数据进行校准。研究结果表明，当两类肝细胞以相同速率增殖时，增殖有助于个体从急性感染中快速恢复；而在慢性感染情况下，若增殖频繁发生，感染的严重程度会增加。另一方面，如果受感染细胞的增殖速率慢于未感染细胞，未感染肝细胞的增殖会促使感染增加，但从长期角度看，受感染肝细胞的增殖则起到减轻感染的作用。此外，还观察到规则增殖与不规则增殖的结果之间存在显著且值得注意的差异。
英文摘要：
Proliferation of uninfected as well as infected hepatocytes and recycling of DNA-containing capsids are two major mechanisms playing significant roles in the clearance of hepatitis B virus (HBV) infection. In this study, the temporal dynamics of this infection are investigated through two in silico bio-mathematical models considering both proliferation of hepatocytes and the recycling of capsids. Both models are formulated on the basis of a key finding in the existing literature: mitosis of infected yields in two uninfected progenies. In the first model, we examine regular proliferation (occurs continuously), while the second model deals with the irregular proliferation (happens when the total number of liver cells decreases to less than 70% of its initial volume). The models are calibrated with the experimental data obtained from an adult chimpanzee. Results of this study suggest that when both hepatocytes proliferate with equal rate, proliferation aids the individual in a rapid recovery from the acute infection whereas in the case of chronic infection, the severity of the infection increases if the proliferation occurs frequently. On the other hand, if the infected cells proliferate at a slower rate than uninfected cells, the proliferation of uninfected hepatocytes contributes to increase the infection, but the proliferation of infected hepatocytes acts to reduce the infection from the long-term perspective. Furthermore, it is also observed that the differences between the outcomes of regular and irregular proliferations are substantial and noteworthy.
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