Abstract
The Epstein-Barr virus (EBV) is a gamma-herpesvirus associated with several malignancies. It establishes a latent infection in B lymphocytes and is occasionally reactivated to enter the lytic cycle. Here we examined the role of the EBV gene BRRF1, which is expressed in the lytic state. We first confirmed, using a DNA polymerase inhibitor, that the BRRF1 gene is expressed with early kinetics. A BRRF1-deficient recombinant virus was constructed using a bacterial artificial chromosome system. No obvious differences were observed between the wild-type, BRRF1-deficient mutant and the revertant virus in HEK293 cells in terms of viral lytic protein expression, viral DNA synthesis, progeny production, pre-latent abortive lytic gene expression and transformation of primary B cells. However, reporter assays indicated that BRRF1 may activate transcription in promoter- and cell type-dependent manners. Taken together, BRRF1 is dispensable for viral replication in HEK293 cells and transformation of B cells, but it may have effects on transcription.
Highlights
The Epstein-Barr virus (EBV) is a ubiquitous human gamma-herpesvirus
To examine the expression kinetics of the BRRF1 gene, B95-8 cells were lytically induced by TPA, A23187 and sodium butyrate (T/A/B) with or without phosphonoacetic acid (PAA), a DNA polymerase inhibitor, for 48 hours (Fig. 1a) as described previously[14]
While induction of L genes (MCP and gp350) by TPA and sodium butyrate (T/B) was suppressed by PAA, induction of E genes (BALF2 and BMRF1) and BRRF1 was not influenced by PAA treatment (Fig. 1b)
Summary
The Epstein-Barr virus (EBV) is a ubiquitous human gamma-herpesvirus. Over 90% of the world’s population is latently infected with EBV. An episome of the EBV DNA exists in the nucleus and expresses only a few latent proteins. EBV enters a transient lytic state[10] called the pre-latent abortive lytic cycle. In this cycle, latent genes and some lytic genes are expressed. Latent genes and some lytic genes are expressed This transient lytic state is silenced by chromatinization, and EBV establishes a latent infection. Human B lymphocytes are transformed into lymphoblastoid cell lines (LCLs), which grow continuously, after EBV infection. This process is called immortalization or transformation. BRRF1 has been reported to localize to the nucleus in HeLa cells[11] or to the nucleus and cytoplasm in Hone-Akata cells[12]
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