Influence of HDACi’s on latent cell reactivation.

<p>(A) The fraction of cells reactivated, <i>f</i>_<i>on</i>, as a function of the fold-increase, <i>ϕ</i>_<i>HDACi</i>, in the rate of HIV-1 transcription, predicted using our stochastic simulations (<a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1006004#sec011" target="_blank">Methods</a>). Representative realizations showing the time-evolution of protein copy numbers in activated (purple) and latent (grey) cells with (B) <i>ϕ</i>_<i>HDACi</i> = 1.24 yielding <i>f</i>_<i>on</i> = 0.066 and (C) <i>ϕ</i>_<i>HDACi</i> = 1.36 yielding <i>f</i>_<i>on</i> = 0.0825. The remaining parameters are in <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1006004#pcbi.1006004.t001" target="_blank">Table 1</a>. Dose-response curves for (D) VPA, (E) NaBut, and (F) TSA, obtained by mapping <i>ϕ</i>_<i>HDACi</i> to the dosage [D] (symbols) that yield the measured <i>f</i>_<i>on</i> [<a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1006004#pcbi.1006004.ref033" target="_blank">33</a>] (<i>Insets</i>). The best-fits of the Hill equation (<a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1006004#pcbi.1006004.e022" target="_blank">Eq (22)</a>) (solid line) and the 95% confidence interval (dashed lines) are also shown. The best-fit parameter estimates are (D) <i>ϕ</i>₀ = 0.57 ± 0.08, <i>ϕ</i>_<i>M</i> = 1.4 ± 0.5 mM (R² = 0.98); (E) <i>ϕ</i>₀ = 1.35 ± 0.08, <i>ϕ</i>_<i>M</i> = 1.1 ± 0.2 mM (R² = 0.99); and (F) <i>ϕ</i>₀ = 2.3 ± 0.4, <i>ϕ</i>_<i>M</i> = 300 ± 100 nM (R² = 0.99).