The Dynamics of EBV Shedding Implicate a Central Role for Epithelial Cells in Amplifying Viral Output

Epstein-Barr virus is a human pathogen associated with several human cancers that nevertheless persists benignly as a latent infection in the majority of adults. EBV persistence is characterized by the presence of latently infected cells in the blood and the shedding of virus into saliva. We present the first systematic quantitative analysis of virus shedding. We show, contrary to what was previously thought, that shedding is continuous and at a high level for all subjects tested. This constant presence of infectious virus may be a crucial risk factor in the development of the EBV-associated tumor nasopharyngeal carcinoma. Unlike infected cells in the blood, which are maintained at very stable levels for years, we show that virus shedding is highly variable such that at any time any individual may be a relatively high or low shedder. We have analyzed these dynamics mathematically and with a simple simulation model. We find that they can be explained by a simple exponential function which we hypothesize is the expansion of 1–3 plaques of epithelial cells.