Figure 2. Models for the impact of population bottlenecks and expansions on viral genetic diversity, during episodes of HSV-1 reactivation and shedding.
During each reactivation event, only a subset of viral genomes begin replication and are transported to epithelial cells. This suggests that a population bottleneck occurs at the start of each reactivation event, with a subsequent population expansion during active viral replication in epithelial cells. We propose three models for how these events may influence genetic diversity in the viral population shed to new hosts. In Model #1, pre-existing genetic variation that was seeded in the ganglia at the time of initial infection undergoes reactivation and may shift in frequency during this bottleneck event. In Model #2, de novo genetic diversity arises during the population expansion within epithelial cells. In Model #3, a superinfection event has occurred, providing either shifting ratios of two HSV-1 genomes, or recombination generating a new HSV-1 genome. We propose that each model could potentially occur across different shedding episodes and between different hosts, creating the genetic fodder that fuels worldwide HSV-1 genome diversity. Image created with BioRender.com.