Mitogen-induced replication of woodchuck hepatitis virus in cultured peripheral blood lymphocytes

Peripheral blood lymphocytes (PBLs) isolated from woodchucks chronically infected with the woodchuck hepatitis virus (WHV) carry low levels of nonreplicating WHV DNA. When PBLs from chronic carrier woodchucks were activated in culture with the generalized mitogen lipopolysaccharide (LPS), WHV DNA replication was initiated in cells obtained from one of three animals examined. Intracellular WHV core particles, containing WHV DNA replication intermediates, RNA/DNA hybrid molecules, and an active endogenous DNA polymerase, appeared 3 days after the start of LPS stimulation. After 5 to 7 days of LPS stimulation, WHV DNA-containing particles, which displayed the properties of intact, mature virions, were released into the culture medium. These studies provide evidence for reactivation of a latent WHV infection of circulating lymphoid cells and indicate that the presence of nonreplicating hepadnaviral DNA in lymphoid cells represents a potentially active infection following cellular activation.