# Quantifying the Sensitivity of HIV-1 Viral Entry to Receptor and Coreceptor Expression

**Authors:** Bhaven Mistry, Maria R. D'Orsogna, Nicholas E. Webb, Benhur Lee, Tom Chou  
**arXiv:** [1805.03281](https://arxiv.org/abs/1805.03281)  
**Date:** 2018-05-08  
**Summary page:** https://www.summarizepaper.com/en/paper/1805.03281v1/

## Key points

- Infection by many viruses involves fusion of viral and cellular lipid membranes, entry of viral contents into target cell, and integration of viral DNA into host cell
- Membrane fusion and viral capsid entry facilitated by adsorption to cell surface, receptor binding, and coreceptor binding
- HIV-1 targets CD4+ helper T-cells in human immune system, binds to CD4 receptor and CCR5 coreceptor before initiating fusion
- Previous experiments conducted using 293-Affinofile cell line to understand relationship between CD4/CCR5 concentrations and infectivity
- Three kinetic models proposed to describe potential mechanistic processes involved in HIV entry
- Models fitted to infectivity measurements from 293-Affinofile cells exposed to different strains of HIV-1 for comparison and contrast
- Model fitting allows interpretation of infectivity clusters among different strains in terms of kinetic parameters and inference regarding receptor/coreceptor binding stoichiometries
- Provides framework for quantitative investigation of effectiveness of fusion inhibitors and neutralizing antibodies on HIV infection dynamics
- Study offers insights into understanding HIV-1 viral entry dynamics and foundation for developing more effective therapeutic strategies targeting this stage

## Summary

Infection by many viruses involves the fusion of viral and cellular lipid membranes, followed by the entry of viral contents into the target cell and integration of viral DNA into the host cell. The initial steps of membrane fusion and viral capsid entry are facilitated by adsorption to the cell surface, as well as receptor and coreceptor binding. HIV-1 specifically targets CD4+ helper T-cells in the human immune system, binding to the receptor CD4 and coreceptor CCR5 before initiating fusion. To better understand the relationship between CD4/CCR5 concentrations and infectivity, previous experiments were conducted using a cell line called 293-Affinofile. This cell line allowed for independent control of CD4 and CCR5 expression levels. After exposing these cells to various strains of HIV-1, researchers measured infectivity by determining the fraction of infected cells. In order to design and evaluate drug therapies that target the inhibition of HIV entry processes, it is crucial to establish an accurate functional relationship between CD4/CCR5 concentrations and infectivity. To achieve this goal, three kinetic models were proposed to describe potential mechanistic processes involved in HIV entry. These models were then fitted to infectivity measurements obtained from 293-Affinofile cells exposed to different strains of HIV-1, allowing for comparison and contrast among different outcomes. This approach not only enables interpretation of how infectivity clusters among different strains of HIV-1 in terms of mechanistic kinetic parameters but also allows for inference regarding nontrivial stoichiometries of receptor and coreceptor binding. Additionally, this model fitting provides a framework through which researchers can quantitatively investigate the effectiveness of fusion inhibitors and neutralizing antibodies on HIV infection dynamics. Overall, this study offers valuable insights into understanding HIV-1 viral entry dynamics and provides a foundation for developing more effective therapeutic strategies targeting this critical stage in infection.