Boettcher Marvin A, Klein Heinrich C R, Schwarz Ulrich S
Institute for Theoretical Physics, Heidelberg University, Germany.
Phys Biol. 2015 Jan 30;12(1):016014. doi: 10.1088/1478-3975/12/1/016014.
Many viruses rely on the self-assembly of their capsids to protect and transport their genomic material. For many viral systems, in particular for human viruses like hepatitis B, adeno or human immunodeficiency virus, that lead to persistent infections, capsomeres are continuously produced in the cytoplasm of the host cell while completed capsids exit the cell for a new round of infection. Here we use coarse-grained Brownian dynamics simulations of a generic patchy particle model to elucidate the role of the dynamic supply of capsomeres for the reversible self-assembly of empty T1 icosahedral virus capsids. We find that for high rates of capsomere influx only a narrow range of bond strengths exists for which a steady state of continuous capsid production is possible. For bond strengths smaller and larger than this optimal value, the reaction volume becomes crowded by small and large intermediates, respectively. For lower rates of capsomere influx a broader range of bond strengths exists for which a steady state of continuous capsid production is established, although now the production rate of capsids is smaller. Thus our simulations suggest that the importance of an optimal bond strength for viral capsid assembly typical for in vitro conditions can be reduced by the dynamic influx of capsomeres in a cellular environment.
许多病毒依靠其衣壳的自组装来保护和运输其基因组物质。对于许多病毒系统,特别是对于像乙型肝炎病毒、腺病毒或人类免疫缺陷病毒等导致持续性感染的人类病毒而言,衣壳粒在宿主细胞的细胞质中持续产生,而完整的衣壳则离开细胞以进行新一轮感染。在此,我们使用一个通用的多斑点粒子模型的粗粒度布朗动力学模拟,来阐明衣壳粒的动态供应对空的T1二十面体病毒衣壳可逆自组装的作用。我们发现,对于衣壳粒流入速率较高的情况,只有在一个狭窄的键强度范围内才可能实现连续衣壳产生的稳态。对于小于和大于此最佳值的键强度,反应体积分别会被小的和大的中间体挤满。对于衣壳粒流入速率较低的情况,存在一个更宽的键强度范围,在此范围内会建立连续衣壳产生的稳态,尽管此时衣壳的产生速率较小。因此,我们的模拟表明,在细胞环境中衣壳粒的动态流入可以降低体外条件下典型的病毒衣壳组装中最佳键强度的重要性。