Estimating the Stoichiometry of Human Immunodeficiency Virus Entry
Estimating the Stoichiometry of Human Immunodeficiency Virus Entry
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DOI：
10.1128/jvi.01764-08
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发表时间：
2009-02-01
影响因子：
5.4
通讯作者：
Regoes, Roland R.
中科院分区：
文献类型：
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作者：
Magnus, Carsten;Rusert, Peter;Regoes, Roland R.
为了进入靶细胞，人类免疫缺陷病毒（HIV）首先附着在细胞上并与细胞膜融合。附着和融合涉及病毒体表面上的包膜糖蛋白三聚体和靶细胞表面上的CD 4受体和趋化因子辅助受体。进入的化学计量，即感染所需的三聚体和CD 4之间的键数，是未知的。假型病毒体表达由功能性和非功能性包膜蛋白组成的混合三聚体，已被用于研究病毒进入需要多少三聚体-受体相互作用。然而，为了从这些病毒的体外感染性测定中产生的数据中提取关于进入的化学计量的信息，需要数学模型。在这里，我们描述的数学模型，可以用来推断的化学计量的进入。通过将我们最简单的模型拟合到以前发布的数据（X。Yang，S.库尔特瓦角Ren，S. Lee和J. Sodroski，J. Virol.七十九：12132-12147，2005），我们估计HIV感染靶细胞所需的三聚体-受体相互作用的数目约为8，这高于先前的估计。我们还考虑模型扩展，解释了一些系统的偏差的数据从最简单的模型的预测。然而，这些扩展的模型产生非常不同的估计化学计量的进入范围从2到19。这些结果强烈表明，根据我们目前对HIV进入的了解，不能可靠地估计该过程的化学计量。我们的研究确定了需要定义的参数，以使估计的HIV进入的化学计量。
To enter target cells, human immunodeficiency virus (HIV) first attaches to the cells and fuses with the cell membrane. Attachment and fusion involve envelope glycoprotein trimers on the surface of the virion and the CD4 receptor and chemokine coreceptors on the surface of the target cell. The stoichiometry of entry, that is, the number of bonds between such trimers and CD4 that are required for infection, is unknown. Pseudotyped virions that express mixed trimers consisting of functional and nonfunctional envelope proteins have been used to study how many trimer-receptor interactions are required for virus entry. However, to extract information on the stoichiometry of entry from data generated in in vitro infectivity assays with such viruses, mathematical models are required. Here, we describe mathematical models that can be used to infer the stoichiometry of entry. By fitting our simplest model to previously published data (X. Yang, S. Kurteva, X. Ren, S. Lee, and J. Sodroski, J. Virol. 79: 12132-12147, 2005), we estimated that the number of trimer-receptor interactions required for HIV to infect a target cell is approximately eight, which is higher than previous estimates. We also consider model extensions that explain some systematic deviations of the data from the prediction of the simplest model. However, these extended models yield very different estimates of the stoichiometry of entry ranging from 2 to 19. These results strongly suggest that, based on our present knowledge of HIV entry, the stoichiometry of this process cannot be reliably estimated. Our study identifies parameters that need to be defined to render the estimation of the stoichiometry of HIV entry possible.