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A Detailed Model and Monte Carlo Simulation for Predicting DIP Genome Length Distribution in Baculovirus Infection of Insect Cells.
Biotechnology and Bioengineering ( IF 3.8 ) Pub Date : 2020-09-16 , DOI: 10.1002/bit.27566
Ashok Das 1 , Soumajit Dutta 2 , Moumita Sen 3 , Abha Saxena 4 , Jitendra Kumar 1 , Lopamudra Giri 4 , David W Murhammer 5 , Jayanta Chakraborty 2
Affiliation  

Baculoviruses have enormous potential for use as biopesticides to control insect pest populations without the adverse environmental effects posed by the widespread use of chemical pesticides. However, continuous baculovirus production is susceptible to DNA mutation and the subsequent production of defective interfering particles (DIPs). The amount of DIPs produced and their genome length distribution are of great interest not only for baculoviruses but for many other DNA and RNA viruses. In this study, we elucidate this aspect of virus replication using baculovirus as an example system and both experimental and modeling studies. The existing mathematical models for the virus replication process consider DIPs as a lumped quantity and do not consider the genome length distribution of the DIPs. In this study, a detailed population balance model for the cell‐virus culture is presented, which predicts the genome length distribution of the DIP population along with their relative proportion. The model is simulated using the kinetic Monte Carlo algorithm, and the results agree well with the experimental results. Using this model, a practical strategy to maintain the DIP fraction to near to its maximum and minimum limits has been demonstrated.

中文翻译:

用于预测昆虫细胞杆状病毒感染中 DIP 基因组长度分布的详细模型和蒙特卡罗模拟。

杆状病毒具有巨大的潜力,可用作生物杀虫剂来控制害虫种群,而不会因广泛使用化学杀虫剂而对环境造成不利影响。然而,连续的杆状病毒生产容易受到 DNA 突变和随后产生的有缺陷的干扰颗粒 (DIP) 的影响。产生的 DIP 的数量及其基因组长度分布不仅对杆状病毒而且对许多其他 DNA 和 RNA 病毒都具有重要意义。在这项研究中,我们使用杆状病毒作为示例系统以及实验和建模研究来阐明病毒复制的这一方面。现有的病毒复制过程数学模型将 DIP 视为一个集总数量,并未考虑 DIP 的基因组长度分布。在这项研究中,提出了细胞病毒培养的详细种群平衡模型,该模型预测了 DIP 种群的基因组长度分布及其相对比例。模型采用动力学蒙特卡罗算法进行模拟,结果与实验结果吻合较好。使用该模型,已经证明了一种将 DIP 分数保持在接近其最大和最小限制的实用策略。
更新日期:2020-09-16
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