Gerg Anthony, Dobrovolny Hana M
Department of Physics & Astronomy, Texas Christian University, Fort Worth, TX 76129, USA.
Viruses. 2025 Apr 18;17(4):583. doi: 10.3390/v17040583.
Human Immunodeficiency Virus (HIV) Type-1 has been studied heavily for decades, yet one area that is still poorly understood is the virus' ability to cause cell-cell fusion. In HIV, the fusion process is mediated by viral surface glycoproteins that bind to CD4 cell receptors. This virus-mediated cell fusion creates multi-nucleated cells called syncytia that can affect infection dynamics. Syncytia formation is often studied using a cell-cell fusion assay, in which donor cells expressing the viral surface protein fuse with acceptor cells expressing the cell receptor. A mathematical model capable of reproducing the dynamics of the cell-cell fusion assay was recently developed and can be used to quantify changes in syncytia formation. In this study, we use this mathematical model to quantify the changes in syncytia formation in HIV as the surface density of the glycoproteins is varied. We find that we need to modify the model to explicitly include a density-dependent syncytia formation rate that allows us to capture the dynamics of the cell-cell fusion assay as the density of the glycoproteins changes. With this modification, we find that cell-cell fusion of the HXB2 strain, which uses the CXCR4 coreceptor, shows a threshold-like behavior, while cell-cell fusion of the Sf162 strain, which uses the CCR5 co-receptor, shows a more gradual change as surface density decreases.
几十年来，人们对1型人类免疫缺陷病毒（HIV）进行了大量研究，但该病毒引发细胞间融合的能力这一领域仍未得到充分理解。在HIV中，融合过程由与CD4细胞受体结合的病毒表面糖蛋白介导。这种病毒介导的细胞融合会产生称为多核体的多核细胞，这可能会影响感染动态。多核体形成通常使用细胞间融合试验进行研究，在该试验中，表达病毒表面蛋白的供体细胞与表达细胞受体的受体细胞融合。最近开发了一种能够再现细胞间融合试验动态的数学模型，可用于量化多核体形成的变化。在本研究中，我们使用该数学模型来量化随着糖蛋白表面密度变化时HIV中多核体形成的变化。我们发现需要修改模型以明确纳入密度依赖性多核体形成速率，这使我们能够在糖蛋白密度变化时捕捉细胞间融合试验的动态。通过这种修改，我们发现使用CXCR4共受体的HXB2毒株的细胞间融合表现出类似阈值的行为，而使用CCR5共受体的Sf162毒株的细胞间融合随着表面密度降低表现出更逐渐的变化。
