Figure 2. An Evolutionary Optimum for Latency.

(A) Numerical solutions to Equation [6] showing the dynamics of latently infected cells in early mucosal infection (R₀^muc = 0.25). As p_lat increases, the number of surviving latently infected cells increases. (Inset) The dynamics of actively infected cells in early mucosal infection showing that as p_lat increases, actively infected cells reach extinction more rapidly.

(B) In systemic infection, (R₀^LT = 10), increases in p_lat decrease the virus load (and, therefore, the viral dose transmitted to the next host). Dynamics in (A and B) are calculated numerically from Equation [6], using the parameters in Table S1 (r = 0).

(C) Schematic flowchart of the derivation of the (optimal) latency probability $p_{\text{lat}}^{\text{opt}}$ that maximizes p_transmission. Red text indicates key assumptions made at each step of the derivation. For example, R₀^muc < < 1 implies that the vast majority of latently infected cells during initial infection are produced in the first generation, leading to the approximation $L_{\mathit{\text{init}}}^{R_0>1}\approx p_{\text{lat}}{I}_0$. The results of the analytic derivation quantify the tradeoff of latency: increasing p_lat linearly increases p_estab but decreases I₀ by the factor (1-p_lat). Since this tradeoff is almost equally balanced, the optimal latency probability, $p_{\text{lat}}^{\text{opt}}$, approximately equals 0.5.

(D) Normalized probability of host-to-host transmission (p_transmission) as a function of p_lat. Results shown are obtained either analytically, from Equation [5] (magenta line), or numerically using the plateau levels of actively infected cells (I) and latently infected cells (L) simulated in A and B (magenta dots). As in C, the probability of transmission is maximized when p_lat ~0.5.

(E) Normalized probability of host-to-host transmission when systemic infections emerge from non-latent routes (e.g., dendritic cells) with probability f_nonlatent > 0 (Equations [S12 and S13]). The maximum probability of transmission occurs at slightly lower p_lat values, but $p_{\text{lat}}^{\text{opt}}$ is still large.

See also Figure S2.