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模拟甲型流感病毒血凝素蛋白介导的流感病毒与健康细胞之间的相互作用:融合前膜变形

Modelling HA protein-mediated interaction between an influenza virus and a healthy cell: pre-fusion membrane deformation.

作者信息

Vaidya Naveen K, Huang Huaxiong, Takagi Shu

机构信息

Department of Mathematics and Statistics, York University, Toronto, Canada M3J 1P3.

出版信息

Math Med Biol. 2007 Sep;24(3):251-70. doi: 10.1093/imammb/dqm002. Epub 2007 Mar 22.

Abstract

We present a mathematical model for pre-fusion interaction between an influenza virus and a healthy cell. Our model describes the role played by hemagglutinin (HA) protein clusters in bringing the viral membrane into close contact with the host cell membrane as a first step of the fusion process between the two membranes. The viral membrane is modelled as a lipid bilayer with bending rigidity. Using the calculus of variations, we compute the deformation of the viral membrane under the influence of HA protein clusters. Our numerical results support the hypothesis of dimple formation in the fusion site proposed in the literature. The asymmetric nature of the protein molecules due to various reasons such as tilting is the primary cause for the dimple formation. We discuss the effects of spontaneous curvature, the protein cluster radius, fusion-site size and the bending moment exerted by the protein cluster. We also examine the effects of membrane tension and the presence of a host cell on the dimple shape. Our results support previous experimental observations.

摘要

我们提出了一种流感病毒与健康细胞之间融合前相互作用的数学模型。我们的模型描述了血凝素(HA)蛋白簇在使病毒膜与宿主细胞膜紧密接触中所起的作用,这是两个膜融合过程的第一步。病毒膜被建模为具有弯曲刚度的脂质双层。利用变分法,我们计算了HA蛋白簇影响下病毒膜的变形。我们的数值结果支持了文献中提出的融合位点形成凹坑的假设。由于倾斜等各种原因导致的蛋白质分子不对称性是凹坑形成的主要原因。我们讨论了自发曲率、蛋白簇半径、融合位点大小以及蛋白簇施加的弯曲力矩的影响。我们还研究了膜张力和宿主细胞的存在对凹坑形状的影响。我们的结果支持了先前的实验观察。

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