Detection of the latent form of Epstein-Barr virus DNA in the peripheral blood of healthy individuals.

Epstein-Barr virus infects resting B cells in vitro and activates them to continuously proliferating lymphoblasts. Activation is essential for the virus to convert its linear genome to the covalently closed circular episomal form in which it persists in proliferating cells. However, in vivo, Epstein-Barr virus persists in resting B cells. We found that in these cells also the virus is present as an episome, suggesting that the cells must, at some time, have been activated and then returned to a resting state. This is the first direct demonstration, for any herpesvirus, of this form of the viral genome in normal persistently infected tissue. Since no linear viral DNA was detected, we estimate that fewer than 1 in 40 cells replicates the virus in the peripheral blood of healthy donors.