Cell-to-cell infection by HIV contributes over half of virus infection
- Kyushu University, Japan
- Japan Science and Technology Agency, Japan
- Kyoto University, Japan
- University of Tokyo, Japan
- Hospital Saint Louis, France
- Université Paris Diderot, Sorbonne Paris Cité, France
- Tokyo University of Agriculture, Japan
Figures
Figure 1
Cell culture systems and the basic reproduction number under cell-to-cell and cell-free infection.
(A) Static and shaking cultures of Jurkat cells. The static and shaking cell cultures allow human immunodeficiency virus type 1 (HIV-1) to perform both cell-free and cell-to-cell infection, and only …
Figure 2 with 3 supplements
Dynamics of HIV-1 infection in Jurkat cells through cell-free and cell-to-cell infection.
Jurkat cells were inoculated with HIV-1 (at multiplicity of infection 0.1) in the static and shaking cell cultures. Panels A and B show the time-course of experimental data for the numbers of …
Figure 2—figure supplement 1
No effect of the shaking procedure on HIV-1 cell-free infection.
Jurkat cells were infected with HIV-1 (at multiplicity of infection 1) as described in ‘Materials and methods’, and the infected cells were cultured in the static and the shaking condition. By …
Figure 2—figure supplement 2
Dynamics of Jurkat cell growth.
Dynamics of Jurkat cell growth in the static and shaking cell cultures. By harvesting the cells for 37 days (A) in the static and (B) in the shaking cell cultures, the growth kinetics of Jurkat …
Figure 2—figure supplement 3
Dot plots of infected cells by flow cytometry.
Representative results of flow cytometry (experiment 1). Time-course results of flow cytometry analyses on experiment 1 of static (left) and shaking (right) cultures are respectively shown. The …
Figure 3
Distribution of the basic reproduction numbers, generation time, and Malthus coefficient.
The distribution of the basic reproduction number, R0, the number of secondary infected cells through the cell-free infection, Rcf, and the cell-to-cell infection, Rcc, calculated from all accepted …
Figure 4
Simulating cell-to-cell infection of HIV-1.
Using our estimated parameters, the pure cell-to-cell infection is simulated in silico (solid curves). The simulated values are located between the time course of experimental data under the static …
Author response image 1
Punctual model for parameter estimation.
The time course of experimental data for the numbers of uninfected cells (top) and infected cells (middle), and the amount of viral p24 antigen (bottom) in the static (left) and shaking (right) …
Tables
Table 1
Parameters estimated by mathematical-experimental analysis
| Parameter name | Symbol | Unit | Exp. 1 | Exp. 2 | Exp. 3 | Ave. ± S.D. |
|---|---|---|---|---|---|---|
| Parameters obtained from simultaneous fit to time-course experimental dataset | ||||||
| Rate constant for cell-free infection | β | 10−6 × (p24 day)−1 | 5.59* (3.54–8.41)† | 3.27 (2.05–5.01) | ‡3.70 (2.28–5.77) | 4.18 ± 1.41 |
| Rate constant for cell-to-cell infection | ω | 10−6 × (cell day)−1 | 0.88 (0.45–1.39) | 1.25 (0.70–1.97) | 1.13 (0.64–1.79) | 1.09 ± 0.33 |
| Production rate of total viral protein | p | day−1 | 0.37 (0.22–0.59) | 0.59 (0.34–0.92) | 0.54 (0.31–0.86) | 0.50 ± 0.16 |
| Death rate of infected cells | δ | day−1 | 0.45 (0.32–0.64) | 0.54 (0.38–0.75) | 0.50 (0.36–0.68) | 0.50 ± 0.10 |
| Quantities derived from fitted values | ||||||
| Basic reproduction number through cell-free infection | Rcf | – | 2.88 (2.34–3.53) | 2.27 (1.98–2.66) | 2.43 (2.04–2.95) | 2.44 ± 0.23 |
| Basic reproduction number through cell-to-cell infection | Rcc | – | 2.95 (1.48–4.70) | 3.65 (1.77–6.05) | 3.39 (1.82–5.38) | 3.39 ± 0.91 |
| Basic reproduction number | R0 | – | 5.83 (4.20–7.75) | 5.92 (3.99–8.46) | 5.83 (4.21–7.89) | 5.83 ± 0.94 |
| Contribution of cell-to-cell infection | – | 0.50 (0.34–0.63) | 0.60 (0.44–0.72) | 0.57 (0.43–0.70) | 0.57 ± 0.07 | |
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*
Mean value.
-
†
95% confidence interval.
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‡
Average and standard deviation of merged values in experiment 1, 2, and 3.
Table 2
Generation time and Malthus coefficient of virus infection
| Cell culture system | Exp. 1 | Exp. 2 | Exp. 3 | Ave. ± S.D. |
|---|---|---|---|---|
| Generation time of HIV-1 | ||||
| Static cell culture | 2.51* days | 2.08 days | 2.22 days | (2.22 ± 0.32)‡ days |
| (1.78–3.38) days | (1.54–2.78) days | (1.69–2.93) days | – | |
| Shaking cell culture | 2.73† days | 2.34 days | 2.47 days | (2.47 ± 0.32) days |
| (1.99–3.59) days | (1.77–3.06) days | (1.91–3.18) days | – | |
| Malthus coefficient of HIV-1 | ||||
| Static cell culture | 1.61 day−1 | 2.03 day−1 | 1.86 day−1 | (1.86 ± 0.37) day−1 |
| (1.10–2.27) day−1 | (1.32–3.01) day−1 | (1.26–2.72) day−1 | – | |
| Shaking cell culture | 0.57 day−1 | 0.46 day−11 | 0.49 day−1 | (0.49 ± 0.05) day−1 |
| (0.47–0.67) day−1 | (0.38–0.56) day−1 | (0.39–0.61) day−1 | – | |
-
*
Mean value.
-
†
95% confidence interval.
-
‡
Average and standard deviation of merged values in experiment 1, 2, and 3.
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HIV-1, human immunodeficiency virus type 1.
Additional files
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Supplementary file 1
Technical details of MCMC computations.
- https://doi.org/10.7554/eLife.08150.012
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Supplementary file 2
Estimated parameter values for Jurkat cell growth.
- https://doi.org/10.7554/eLife.08150.013
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Supplementary file 3
Estimated initial values for HIV-1 infection.
- https://doi.org/10.7554/eLife.08150.014
