Latent and lytic Epstein‐Barr virus replication strategies

Abstract

The Epstein-Barr virus (EBV) can choose between two alternative lifestyles; latent or lytic replication. In the latent state, the EBV genomic DNA, which exists as a closed circular plasmid, appears to behave just like host chromosomal DNA and it has been demonstrated recently that replication of OriP-containing plasmids is indeed dependent on the chromosomal initiation factors, ORC2 and Cdt1. On the other hand, in the viral productive cycle, the EBV genome is amplified 100- to 1000-fold by the viral replication machinery. EBV productive DNA replication occurs at discrete sites in nuclei, called replication compartments and the lytic programme arrests cell cycle progression and changes the cellular environment greatly. It has been revealed recently that the EBV lytic programme promotes an S-phase like cellular condition, which most favours viral lytic replication. This review describes recent advances regarding the molecular basis of EBV DNA replication during latent and lytic infections and then refers to cellular circumstances after induction of the lytic replication of EBV. Based on the molecular mechanism for the EBV lifestyle, purposeful induction of the lytic form of EBV infection is now advocated as one of the strategies for specific destruction of Epstein-Barr virus (EBV)-associated malignancies where the virus is latently infected.

Regulation of cellular and viral protein expression by the Epstein-Barr virus transcriptional regulator Zta: Implications for therapy of EBV associated tumors

“…The results from this study showed that the levels of p53, p21 WAF-1/CIP-1 and p27 KIP-1 were unchanged before and after induction of the lytic program, whereas elevation of cyclin E/A expression and accumulation of hyperphosphorylated Rb protein were observed. 91 Zta expression in HeLa cells markedly reduced the expression of the cyclin B1 both at RNA and protein levels, indicating that Zta induced a G 2 block in HeLa cells by decreasing the level of cyclin B1. 92 It appeared that the effect of Zta expression on cell cycle progression could occur in different phases of the cell cycle (either G 0 /G 1 or G 2 /M) in a cell type dependent manner.…”

(-)-Epigallocatechin‑3‑gallate inhibition of Epstein‑Barr virus spontaneous lytic infection involves downregulation of latent membrane protein 1

“…1A). Additionally, the constructed CNE1-LMP1 cell line that constitutively expressed LMP1 exhibited markedly increased expression levels of the EBV lytic proteins BZLF1 and BMRF1 (37,38) when compared with the CNE1 control cells (Fig. 1B).…”

TLR9 triggering in Burkitt's lymphoma cell lines suppresses the EBV BZLF1 transcription via histone modification

“…Upon reactivation, the EBV immediate-early gene BZLF1 (encoding the protein Zta), the master regulatory lytic gene, is the very first viral lytic gene expressed (Rickinson and Kieff, 2007). It encodes transcription factors that induce an ordered cascade of early and late lytic EBV genes expressions (Tsurumi et al, 2005). Notably, in cell lines infected with latent EBV, the virus can be induced to lytic infection by stimuli such as anti-immunoglobulin (Ig), transforming growth factor-b (TGFb), 12-O-tetradecanoylphorbol-13-acetate or sodium butyrate (SB) (Tovey et al, 1978;zur Hausen et al, 1978;Luka et al, 1979;Takada, 1984;di Renzo et al, 1994).…”