Model predictions of CLDN1 expression on infected and uninfected cells.

<p>(A) Time-evolution of the mean CLDN1 expression level on infected (orange) and uninfected (blue) cells. (B) Average CLDN1 expression on twenty cells sampled from the infected (orange) and uninfected (blue) populations at different post-infection times. Error bars represent standard deviations. Parameters and initial conditions employed were the same as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0036107#pone-0036107-g002" target="_blank">Fig. 2</a>.</p

Evolution of the distribution of CLDN1 expression.

<p>Model predictions (lines) of the normalized distribution of the CLDN1 expression on cells at day 1 (blue), day 3 (light green), and at day 5 (dark green) post-infection, the latter fit to corresponding experimental data <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0036107#pone.0036107-Liu1" target="_blank">[16]</a> (green cricles). The best-fit parameter estimates are fluorescence units and . The other parameters employed are listed in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0036107#pone-0036107-t001" target="_blank">Table 1</a>. Initial conditions were the same as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0036107#pone-0036107-g002" target="_blank">Fig. 2</a>. Inset (A) shows the normalized distribution of CLDN1 expression on mock infected cells () at all post-infection times (lines overlap and are indistinguishable). Inset (B) shows the residual (symbols) of the best-fit to the experimental data; the mean error is and is not significantly different from zero (line) ( using the two tailed t-test).</p

Model predictions of HCV viral kinetics in vitro.

<p>The time evolution of (A) uninfected cells, , (B) infected cells, , and viral load, , (C) uninfected cell subpopulations, (solid line), and infected cell subpopulations, (dashed line), corresponding to (red) and (cyan) and (D) total subpopulations, , corresponding to (red) and (cyan). The three phases of infection are marked in (A). Initial conditions: . Parameters employed are listed in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0036107#pone-0036107-t001" target="_blank">Table 1</a>.</p

Expression of CLDN1 on cells and their susceptibility to infection.

<p>Best-fit (red line) of the normalized distribution of CLDN1 expression, , where is the maximum value of , to experimental data <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0036107#pone.0036107-Liu1" target="_blank">[16]</a> (red circles). The best-fit parameter estimates (95% CI) are , , , , , and . The corresponding susceptibility, , as a function of CLDN1 expression is also shown (black line). (Inset) Residuals (symbols) of the best-fit to experimental data; the mean error is and is not significantly different from zero (line) ( using the two tailed t-test).</p

Electronic supplementary materials from Axon growth regulation by a bistable molecular switch

Electronic supplementary material

Summary of model parameters and their values employed.

<p>Summary of model parameters and their values employed.</p

Electronic supplementary materials from Axon growth regulation by a bistable molecular switch

Electronic supplementary material

Response to DAA-based treatments.

<p>SVR rates elicited by various IFN-free and IFN-containing DAA combinations in treatment-naïve and prior null responders to PR from recent clinical trials. The treated population size is indicated in brackets. The significance of the difference in the SVR rates in the two populations is computed using the χ² test. The HCV genotype and whether the patients had liver cirrhosis is indicated. The details of the treatment regimens along with the sources of the data are in <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1006335#pcbi.1006335.s004" target="_blank">S1 Table</a>.</p

Response to PR+DAA treatment.

<p><b>(A)</b> Phase diagram indicating regimes of IFN-responsiveness pre- and during treatment, and , leading to SVR (dark blue) and treatment failure due to virological breakthrough by the RAV (light blue) for a fixed relative fitness of the RAV during treatment, <i>γ</i>_<i>t</i>. <b>(B)</b> Dynamics of wild-type (solid) and RAV (dashed) viral populations following treatment initiation for parameter combinations numbered in (A). <b>(C)</b> Phase diagram on a plot for fixed . <b>(D)</b> Dynamics for the points numbered in (C). In (A)-(D), the DAA efficacy against the wild-type, . Also, <i>γ</i> = 0.4. <b>(E)-(H)</b> Corresponding predictions with . In (E) and (G), treatment failure occurred due to the RAV (light blue), wild-type (green), or both (brown). Here, <i>γ</i> = 0.2. Other parameter values employed are in <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1006335#pcbi.1006335.s008" target="_blank">S5 Table</a>. Phase diagrams for other values of are in <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1006335#pcbi.1006335.s003" target="_blank">S3 Fig</a>.</p

Pre-treatment frequencies and populations of virions.

<p>Model predictions (lines) and analytical approximations (symbols) (<a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1006335#pcbi.1006335.s009" target="_blank">S1</a>–<a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1006335#pcbi.1006335.s011" target="_blank">S3 Texts</a>) of the mutant frequencies (left) and viral populations (right) in the pre-treatment steady state as a function of the level of IFN-responsiveness, , for different combinations of the mutation rate, <i>μ</i>, and the relative fitness of the RAV, <i>γ</i>: (<i>μ</i>,<i>γ</i>) = (3×10⁻⁴,0.9) (blue), (3×10⁻⁴,0.8) (red), (3×10⁻⁴,0.7) (green) and (3×10⁻⁵,0.8) (black). Here, <i>γ</i> = <i>p</i>₁/<i>p</i>₀, the ratio of the viral production rates, or equivalently the replicative abilities, of the mutant and wild-type strains; without loss of generality, the RAV was assumed not to compromise viral infectivity (see <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1006335#pcbi.1006335.s009" target="_blank">S1</a>–<a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1006335#pcbi.1006335.s011" target="_blank">S3 Texts</a>). Single mutant frequencies (<b>A)</b> and the populations of wild-type <b>(B)</b> and single mutant <b>(C)</b> virions when the genetic barrier is 1. Double mutant frequencies <b>(D)</b> and the populations of wild-type <b>(E)</b>, single mutant <b>(F)</b>, and double mutant <b>(G)</b> virions when the genetic barrier is 2. In the latter case, the two single mutants have the same relative fitness, <i>γ</i>, and the double mutant, <i>γ</i>². In (B) and (E), the different lines and symbols are indistinguishable. Parameter values employed are in <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1006335#pcbi.1006335.s008" target="_blank">S5 Table</a>. The parameters to which these predictions are sensitive are as expected from the analytical approximations (<a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1006335#pcbi.1006335.s001" target="_blank">S1 Fig</a>).</p