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Updated: Feb 25, 2026
Ex Vivo Infection of Human Lymphoid Tissue and Female Genital Mucosa with Human Immunodeficiency Virus 1 and Histoculture
Published on: October 12, 2018
Number of infection events per cell during HIV-1 cell-free infection
Yusuke Ito1, Azaria Remion2,3,4, Alexandra Tauzin2,3,4
1Department of Biology, Faculty of Sciences, Kyushu University, Fukuoka, 819-0395, Japan.
Insights
Coinfection with human immunodeficiency virus type 1 (HIV-1) is non-random, driven by target cell susceptibility. A new mathematical model explains this non-randomness, showing infection events follow a negative-binomial distribution.
Area of Science:
- Virology
- Mathematical Biology
- Immunology
Background:
- Human immunodeficiency virus type 1 (HIV-1) genetic changes occur via mutation and recombination.
- Recombination requires single-cell coinfection by two HIV-1 strains.
- Observed coinfection events are more frequent and non-random than expected by chance.
Purpose of the Study:
- To develop a quantitative framework for understanding non-random HIV-1 coinfection.
- To explicitly model target cell heterogeneity in HIV-1 infection dynamics.
- To analyze experimental data of cell-free HIV-1 single and double infections.
Main Methods:
- Developed a novel mathematical model incorporating continuous target cell susceptibility distribution.
- Analyzed existing experimental datasets of cell-free HIV-1 infection.
- Compared model predictions with experimental outcomes for single and double infections.
Main Results:
- Target cell susceptibility differences explain the non-random distribution of coinfection events.
- The number of infection events per cell in cell-free HIV-1 infection follows a negative-binomial distribution.
- The developed mathematical model successfully reproduces experimental datasets.
Conclusions:
- Heterogeneity in target cell susceptibility is a key driver of non-random HIV-1 coinfection.
- The negative-binomial distribution accurately describes HIV-1 infection events per cell.
- This quantitative framework enhances understanding of HIV-1 transmission dynamics.
Abstract:
HIV-1 accumulates changes in its genome through both recombination and mutation during the course of infection. For recombination to occur, a single cell must be infected by two HIV strains. These coinfection events were experimentally demonstrated to occur more frequently than would be expected for independent infection events and do not follow a random distribution. Previous mathematical modeling approaches demonstrated that differences in target cell susceptibility can explain the non-randomness, both in the context of direct cell-to-cell transmission, and in the context of free virus transmission (Q. Dang et al., Proc. Natl. Acad. Sci. USA 101:632-7, 2004: K. M. Law et al., Cell reports 15:2711-83, 2016). Here, we build on these notions and provide a more detailed and extensive quantitative framework. We developed a novel mathematical model explicitly considering the heterogeneity of target cells and analysed datasets of cell-free HIV-1 single and double infection experiments in cell culture. Particularly, in contrast to the previous studies, we took into account the different susceptibility of the target cells as a continuous distribution. Interestingly, we showed that the number of infection events per cell during cell-free HIV-1 infection follows a negative-binomial distribution, and our model reproduces these datasets.
