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Quantifying Impact of HIV Receptor Surface Density Reveals Differences in Fusion Dynamics of HIV Strains
Anthony Gerg1, Hana M Dobrovolny1
1Department of Physics & Astronomy, Texas Christian University, Fort Worth, TX 76129, USA.
Insights
Understanding Human Immunodeficiency Virus (HIV) cell-cell fusion is crucial. This study quantifies syncytia formation dynamics by modifying a mathematical model to include density-dependent rates, revealing strain-specific fusion behaviors.
Area of Science:
- Virology
- Mathematical Biology
- Immunology
Background:
- Human Immunodeficiency Virus (HIV) Type-1 infection dynamics are influenced by cell-cell fusion, a poorly understood process.
- Viral glycoproteins mediate HIV-induced fusion, leading to syncytia formation, which impacts infection progression.
- Syncytia formation is typically assessed via cell-cell fusion assays, quantifying the interaction between virus-expressing cells and receptor-bearing cells.
Purpose of the Study:
- To quantify changes in HIV syncytia formation by varying viral surface glycoprotein density.
- To refine a mathematical model for cell-cell fusion assays by incorporating density-dependent syncytia formation rates.
- To investigate strain-specific differences in HIV cell-cell fusion dynamics.
Main Methods:
- Utilized a recently developed mathematical model for cell-cell fusion assays.
- Modified the model to explicitly include a density-dependent syncytia formation rate.
- Quantified syncytia formation by varying the surface density of viral glycoproteins for different HIV strains.
Main Results:
- The modified mathematical model accurately captured syncytia formation dynamics across varying glycoprotein densities.
- HIV HXB2 strain (CXCR4 coreceptor) exhibited threshold-like cell-cell fusion behavior with decreasing surface density.
- HIV Sf162 strain (CCR5 co-receptor) demonstrated a more gradual decrease in cell-cell fusion as surface density was reduced.
Conclusions:
- A density-dependent syncytia formation rate is essential for accurately modeling HIV cell-cell fusion dynamics.
- HIV strains display distinct cell-cell fusion patterns based on coreceptor usage and glycoprotein density.
- This refined model provides a quantitative tool to study HIV fusion mechanisms and potential therapeutic targets.
Abstract:
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.
