Modeling the dynamics of virus shedding into the saliva of Epstein-Barr virus positive individuals.

Epstein-Barr virus (EBV) can infect both B cells and epithelial cells. Infection of B cells enables the virus to persist within a host while infection of epithelial cells is suggested to amplify viral output. Data from a recent study have shown that the virus shedding in EBV positive individuals is relatively stable over short periods of time but varies significantly over long periods. The mechanisms underlying the regulation of virus shedding within a host are not fully understood. In this paper, we construct a model of ordinary differential equations to study the dynamics of virus shedding into the saliva of infected hosts. Infection of epithelial cells is further separated into infection by virus released from B cells and virus released from epithelial cells. We use the model to investigate whether the long-term variation and short-term stability of virus shedding can be generated by three possible factors: stochastic variations in the number of epithelial cells susceptible to virus released from infected B cells, to virus released from infected epithelial cells, or random variation in the probability that CD8(+) T cells encounter and successfully kill infected cells. The results support all three factors to explain the long-term variation but only the first and third factors to explain the short-term stability of virus shedding into saliva. Our analysis also shows that clearance of virus shedding is possible only when there is no virus reactivation from B cells.