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丙型肝炎病毒 NS5A 蛋白在 ER 表面的动态定量分析。

Quantitative Analysis of Hepatitis C NS5A Viral Protein Dynamics on the ER Surface.

机构信息

Goethe Center for Scientific Computing (G-CSC), Goethe Universität Frankfurt, Kettenhofweg 139, 60325 Frankfurt am Main, Germany.

Ruhr-Universität Bochum, High Performance Computing in the Engineering Sciences, Universitätsstrasse 150, 44801 Bochum, Germany.

出版信息

Viruses. 2018 Jan 8;10(1):28. doi: 10.3390/v10010028.

DOI:10.3390/v10010028
PMID:29316722
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5795441/
Abstract

Exploring biophysical properties of virus-encoded components and their requirement for virus replication is an exciting new area of interdisciplinary virological research. To date, spatial resolution has only rarely been analyzed in computational/biophysical descriptions of virus replication dynamics. However, it is widely acknowledged that intracellular spatial dependence is a crucial component of virus life cycles. The hepatitis C virus-encoded NS5A protein is an endoplasmatic reticulum (ER)-anchored viral protein and an essential component of the virus replication machinery. Therefore, we simulate NS5A dynamics on realistic reconstructed, curved ER surfaces by means of surface partial differential equations (sPDE) upon unstructured grids. We match the in silico NS5A diffusion constant such that the NS5A sPDE simulation data reproduce experimental NS5A fluorescence recovery after photobleaching (FRAP) time series data. This parameter estimation yields the NS5A diffusion constant. Such parameters are needed for spatial models of HCV dynamics, which we are developing in parallel but remain qualitative at this stage. Thus, our present study likely provides the first quantitative biophysical description of the movement of a viral component. Our spatio-temporal resolved ansatz paves new ways for understanding intricate spatial-defined processes central to specfic aspects of virus life cycles.

摘要

探索病毒编码成分的生物物理特性及其对病毒复制的要求是跨学科病毒学研究的一个令人兴奋的新领域。迄今为止，在病毒复制动力学的计算/生物物理描述中，空间分辨率很少被分析。然而，人们普遍认识到，细胞内的空间依赖性是病毒生命周期的一个关键组成部分。丙型肝炎病毒编码的 NS5A 蛋白是一种内质网 (ER) 锚定的病毒蛋白，也是病毒复制机制的重要组成部分。因此，我们通过非结构网格上的曲面偏微分方程 (sPDE) 模拟 NS5A 在真实重建的弯曲 ER 表面上的动力学。我们匹配了 NS5A 的扩散常数，使得 NS5A 的 sPDE 模拟数据能够重现实验性的 NS5A 荧光恢复后光漂白 (FRAP) 时间序列数据。这种参数估计得到了 NS5A 的扩散常数。这些参数对于正在并行开发的 HCV 动力学的空间模型是必要的，但在现阶段仍然是定性的。因此，我们目前的研究可能为病毒成分的运动提供了第一个定量的生物物理描述。我们的时空分辨方案为理解病毒生命周期中特定方面的复杂空间定义过程开辟了新的途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b87/5795441/eab869e71218/viruses-10-00028-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b87/5795441/40c27e392c02/viruses-10-00028-g0A1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b87/5795441/3fb28ec494da/viruses-10-00028-g0A2.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b87/5795441/45f18d33741a/viruses-10-00028-g0A5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b87/5795441/cddc90e39ed9/viruses-10-00028-g0A6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b87/5795441/e420682176c5/viruses-10-00028-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b87/5795441/b5aa09be25db/viruses-10-00028-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b87/5795441/1db810fe343c/viruses-10-00028-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b87/5795441/aab51573bb40/viruses-10-00028-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b87/5795441/8baa5e4f6003/viruses-10-00028-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b87/5795441/78b84a905ee8/viruses-10-00028-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b87/5795441/3d0113c0c285/viruses-10-00028-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b87/5795441/eab869e71218/viruses-10-00028-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b87/5795441/40c27e392c02/viruses-10-00028-g0A1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b87/5795441/3fb28ec494da/viruses-10-00028-g0A2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b87/5795441/024cd9a83dfa/viruses-10-00028-g0A3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b87/5795441/2a39e419db7e/viruses-10-00028-g0A4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b87/5795441/45f18d33741a/viruses-10-00028-g0A5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b87/5795441/cddc90e39ed9/viruses-10-00028-g0A6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b87/5795441/e420682176c5/viruses-10-00028-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b87/5795441/b5aa09be25db/viruses-10-00028-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b87/5795441/1db810fe343c/viruses-10-00028-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b87/5795441/aab51573bb40/viruses-10-00028-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b87/5795441/8baa5e4f6003/viruses-10-00028-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b87/5795441/78b84a905ee8/viruses-10-00028-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b87/5795441/3d0113c0c285/viruses-10-00028-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b87/5795441/eab869e71218/viruses-10-00028-g008.jpg

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