The Epstein-Barr virus nuclear antigen (EBNA) 3B is a hydrophilic, proline-rich, charged protein that is thought to be involved in transcriptional regulation and is targeted exclusively to the cell nucleus, where it localizes to discrete subnuclear granules. Co-localization studies utilizing a fusion protein between enhanced green fluorescent protein (EGFP) and EBNA3B with FLAG-tagged EBNA3A and EBNA3C proteins demonstrated that EBNA3B co-localized with both EBNA3A and EBNA3C in the nuclei of cells when overexpressed. Computer analyses identified four potential nuclear-localization signals (NLSs) in the EBNA3B amino acid sequence. By utilizing fusion proteins with EGFP, deletion constructs of EBNA3B and site-directed mutagenesis, three of the four NLSs (aa 160-166, 430-434 and 867-873) were shown to be functional in truncated forms of EBNA3B, whilst an additional NLS (aa 243-246) was identified within the N-terminal region of EBNA3B. Only two of the NLSs were found to be functional in the context of the full-length EBNA3B protein. (Henle & Henle, 1979) and is also associated with several human malignancies, including Burkitt's lymphoma (BL), nasopharyngeal carcinoma and immunoblastic B-cell lymphomas in immunocompromised individuals (Macsween & Crawford, 2003). EBV infections result in a lifelong carrier state whereby the virus exists in a latent state in B cells. EBV is able to efficiently transform and immortalize human B cells in vitro, resulting in the generation of lymphoblastoid cell lines. Despite the presence of the complete viral genome in EBV-immortalized B lymphocytes, only a limited number of viral genes are expressed. These include the latent proteins EBV nuclear antigens (EBNAs) 1, 2, 3A, 3B, 3C and LP, two latent membrane proteins (LMP-1 and -2) and the EBER RNAs and the BamHI A rightward transcripts (BARTs).
Epstein-Barr virus (EBV) is a lymphotrophic herpesvirus that is the causative agent of infectious mononucleosisEBNA3A, 3B and 3C share a similar genomic organization, they have molecular masses between 135 and 165 kDa and are hydrophilic, proline-rich, charged proteins. Each of the EBNA3 proteins interacts with the DNA-binding protein RBP-Jk/RBP-2N (also known as CBF1) (Johannsen et al., 1996;Krauer et al., 1996;Robertson et al., 1995;Young et al., 1997), indicating that they play a role in transcriptional regulation (Krauer et al., 1998;Marshall & Sample, 1995). The EBNA3B protein is non-essential for EBV-mediated Bcell growth transformation in vitro (Hsu et al., 2005), although the persistent expression of EBNA3B against negative selective pressure by cytotoxic T cells in vivo is consistent with an important role for this gene product. EBNA3B has been shown to be capable of disrupting a drug-induced G 2 /M checkpoint (Krauer et al., 2004b), to upregulate expression of the cytoskeletal protein vimentin and the activation antigen CD40 and to cause downregulation of the BL-associated antigen BLA (CD77) (Silins & Sculley, 1994, 1995.The EBNA3B protein is targeted exclusively to the cell nucleu...