Selective switch between latency and lytic replication of Kaposi's sarcoma herpesvirus and Epstein-Barr virus in dually infected body cavity lymphoma cells

Abstract

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 between these two gammaherpesviruses and BC-1 cells were characterized and compared. Single-cell cloning experiments suggested that all BC-1 cells contain both genomes. In more than 98% of cells, both viruses were latent. The two viruses could be differentially induced into their lytic cycles by chemicals. EBV was activated into DNA replication and late-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 n-butyrate was accompanied by the disappearance of host-cell ␤-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. Recognition of one of these, p40, served as the basis of development of an 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-butyratetreated 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 latency to lytic cycle.

In primary effusion lymphoma cells, MYB transcriptional repression is associated with v‐FLIP expression during latent KSHV infection while both v‐FLIP and v‐GPCR become involved during the lytic cycle

“…KSHV encodes at least two proteins that have the ability of activating the NF‐ κ B pathway: v‐FLIP, which is expressed both at the latent and the lytic KSHV stages (Liu et al , 2002), and v‐GPCR (Schwarz & Murphy, 2001), which is only expressed at the early lytic stage (Nador et al , 1996; Paulose‐Murphy et al , 2001). To determine the correlation between v‐FLIP or v‐GPCR expression and MYB levels, PEL cells were treated with TPA, an inducer of the lytic cycle (Miller et al , 1997; Yu et al , 1999; Paulose‐Murphy et al , 2001). Following TPA treatment, MYB levels significantly decreased in all PEL cell lines tested (Fig 1A, see lanes 3, 5, 7, 9, 11 versus 2, 4, 6, 8, 10 and Fig 1C for quantification).…”

Distinct Roles for Extracellular Signal-Regulated Kinase 1 (ERK1) and ERK2 in the Structure and Production of a Primate Gammaherpesvirus

“…T he gammaherpesvirus, Kaposi's sarcoma-associated herpesvirus (KSHV), is the causative agent of three human malignancies, most notably Kaposi's sarcoma (KS), an AIDS-defining disease (10,11,21,22,44,45,58,59). Since even the best source of KSHV virions tends to yield titers that are often less than 10E5/ml (1), primate homologs such as rhesus monkey rhadinovirus (RRV), which favor lytic rather than latent infection in culture, often serve as a model system for studying virus structure and protein composition (16,50).…”

Inhibition of replication and transcription activator and latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus by morpholino oligomers

“…Proinflammatory cytokines are considered to be essential for the development of KSHV-associated malignancies (Ensoli et al, 1991;Moore et al, 1996). In KSHV-infected PEL cells and in KS lesions, a low percentage (<5%) of cells maintain KSHV lytic replication (Miller et al, 1997). Lytic cycle activation is a pivotal event in the cascade of events involved with KSHV replication.…”