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A kinetic and statistical-thermodynamic model for baculovirus infection and virus-like particle assembly in suspended insect cells 收藏

在悬浮昆虫细胞为杆状病毒感染和病毒样颗粒装配的动力学和统计热力学模型
摘要
Virus-like particles (VLPs) are self-assembled structures comprised of virus capsid proteins that closely resemble native virus but are devoid of native viral RNA or DNA and therefore have attracted significant attention as noninfectious vaccines. A mathematical model that characterizes baculovirus infection, protein synthesis and VLP assembly in insect cells was developed. The probability of infection was described by a Poisson distribution and the infected cell population was segregated by the time of infection and the number of infecting viruses in order to examine the contributions of individual cells. Predictions relating to cell growth, virus infection efficiency (tracked by immunofluorescence labeling), replication kinetics, substrate consumption, and cell death in suspended batch cultures agreed well with experiments. For efficient primary infection with virus, a multiplicity of infection (MOI) of 2.5 was necessary. The optimal harvest timing occurred at 40–70% cell viability. The assembly of VLPs comprised of the structural proteins (VP2 and VP3) of the infectious bursal disease virus (IBDV) using a thermodynamically based equilibrium model was described. The complete model suggested that the formation of IBD VLP was thermodynamically favorable and predicted well the baculovirus infection in individual cells or in the culture as a whole. This model can potentially be used to further describe and optimize VLP formation for other virus pathogens.
摘要译文
由病毒衣壳蛋白酷似天然病毒,但缺乏天然病毒RNA或DNA,因此对结构已经吸引了显著关注,因为非传染性疫苗。被开发为特征杆状病毒感染,蛋白质合成和组装VLP在昆虫细胞中的数学模型。通过泊松分布刻划和感染细胞群体分离的感染的时间,以便检查各个单元的贡献感染病毒的数量。与细胞生长,病毒感染效率(通过免疫荧光标记跟踪),复制动力学,基质消耗的预测,和细胞死亡的悬浮分批培养同意很好地与实验。对于与病毒高效原发感染,感染复数(MOI)为2.5是必要的。最佳收获定时发生在40%-70%细胞生存力。的VLP包含使用热力学基于均衡模型的感染性囊病病毒(IBDV)的结构蛋白(VP2和VP3)的组件被描述。完整的模型表明,IBD VLP的形成是热力学有利和预测以及杆状病毒感染单个细胞或文化作为一个整体。这个模型可以潜在地用于进一步描述和优化的VLP形成为其他病毒病原体。
Yu-Chen Hu[a][b]; William E. Bentley[a][b]. A kinetic and statistical-thermodynamic model for baculovirus infection and virus-like particle assembly in suspended insect cells[J]. Chemical Engineering Science, 2000,55(19): 3991–4008