Number of infection events per cell during HIV-1 cell-free infection
Human Immunodeficiency Virus type 1 (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. Although the heterogeneity of target cell susceptibility was proposed as a possible mechanism for the non-randomness, the quantitative evaluation of its impact on coinfection frequency is lacking, especially for cell-free infection in vitro. Here, we developed a novel mathematical model considering the heterogeneity of target cells and analysed datasets of cell-free HIV-1 single and double infection experiments in cell culture. Interestingly, we showed that the number of infection events per cell during cell-free HIV-1 infection follows a negative-binomial distribution, and our novel model reproduces these datasets. Furthermore, our quantitative analyses reveal that the average number of infection events increases from 1.02 to 1.65 as the amount of inoculated HIV-1 increases, and the multiple infection frequency increases to 17%. These findings demonstrate that cell-free HIV-1 infection has an important role in driving virus recombination. Therefore, spatially separated HIV-1 variants from different organs might be able to recombine within patients via cell-free infection.
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