Within-host demographic fluctuations and correlations in early retroviral infection

In this paper we analyze the demographic fluctuations and correlations present in within-host populations of viruses and their target cells during the early stages of infection. In particular, we present an exact treatment of a discrete-population, stochastic, continuous-time master equation description of HIV or similar retroviral infection dynamics, employing Monte Carlo simulations. The results of calculations employing Gillespie's direct method clearly demonstrate the importance of considering the microscopic details of the interactions which constitute the macroscopic dynamics. We then employ the τ-leaping approach to study the statistical characteristics of infections involving realistic absolute numbers of within-host viral and cellular populations, before going on to investigate the effect that initial viral population size plays on these characteristics. Our main conclusion is that cross-correlations between infected cell and virion populations alter dramatically over the course of the infection. We suggest that these statistical correlations offer a novel and robust signature for the acute phase of retroviral infection.

► Discrete virion and cell numbers result in demographic fluctuations. ► Give rise to non-zero variance and cross-correlations. ► These persist even when conditioning on infection survival. ► Correlation between infected cells and virions forms signature for acute phase.