Early Viral Transmissions May Provide a Positive Impact on the Quasispecies Mutational Fitness Landscape

It is known that for RNA viruses, such as HIV and HCV, the early or acute infection period may be correlated to higher transmissibility regarding chronic or late stages. However, studies of the impact of fitness effects caused by mutations on viral particles over transmission events are lacking. Our goal is to verify whether the passing of time can change the quality of viral particles and promote impact on an epidemic. We propose to address this question through a two-level mathematical model based on RNA viral population dynamics. The first level of the model represents the intra-host viral population dynamics and the second level represents the host-to-host dynamics of transmission events. The intra-host dynamics model uses the fitness of viral particles to track the presence of highly infective particles during transmission bottlenecks. More specifically, the intra-host dynamics is described by stochastic quasispecies, based on a multivariate branching process. The host-to-host dynamics of transmission events are emulated by a putative transmission tree with a ‘host zero’ at the root and a fixed number of branches emanating from each internal node. A Monte Carlo Markov Chain strategy was adopted to explore the tree by sampling random walks along transmission chains along the tree. Viral infections of a single host and several transmission events among hosts were simulated in early and late infection stages scenarios. The results show that the early infection stages may represent a key factor in a viral epidemic. Over the evolution of the viral population within each host the mean fitness decreases due to the occurrence of mutations (most of them causing deleterious effects). Despite the small opportunity interval, early-stage transmissions could infect new hosts at a higher rate than in late stages. It was observed that a very early transmission scenario could reach a transmission chain 20 times longer than a very late transmission scenario. This indicates that the quality of the viral particles is a relevant factor for transmission events.