SELECTIVE SWITCH BETWEEN LATENCY AND LYTIC REPLICATION OF KAPOSIS-SARCOMA HERPESVIRUS AND EPSTEIN-BARR-VIRUS IN DUALLY INFECTED BODY CAVITYLYMPHOMA-CELLS

The BC-1 cell line, derived from a body cavity-based, B-cell lymphoma, is dually infected with Epstein-Barr virus (EBV) and Kaposi's sarcoma -associated herpesvirus (KSHV). In these studies, the relationships be tween these two gammaherpesviruses and BC-1 cells were characterized a nd compared, Single cell cloning experiments suggested that all BC-1 c ells contain both genomes. In more than 98% of cells, both viruses wer e latent. The two viruses could be differentially induced into their l ytic cycles by chemicals. EBV was activated into DNA replication and l ate-gene expression by the phorbol ester tetradecanoyl phorbol acetate (TPA). KSHV was induced into DNA replication and late-gene expression by n-butyrate. Amplification of both EBV and KSHV DNAs was inhibited by phosphonoacetic acid. Induction of the KSHV lytic cycle by II-butyr ate was accompanied by the disappearance of host-cell beta-actin mRNA. Induction of EBV by TPA was not accompanied by such an effect on host -cell gene expression. Induction of the KSHV lytic cycle by n-butyrate was associated with the expression of several novel polypeptides. Rec ognition of one of these, p40, served as the basis of development of a n assay for antibodies to KSHV in the sera of infected patients. BC-1 cells released infectious EBV; however, there was no evidence for the release of encapsidated KSHV genomes by BC-1 cells, even though n-buty rate-treated cells contained numerous intranuclear nucleocapsids. The differential inducibility of these two herpesviruses in the same cell line points to the importance of viral factors in the switch from late ncy to lytic cycle.