Genome and gene expression of EBV
In: Bioscience
The EBV is a herpes virus of the gamma subfamily. Icosahedral virus is a package that contains a linear double-stranded DNA of 172,000 base pairs. Once infected the cell, the viral DNA is transported to the nucleus where available primarily as a circular extrachromosomal molecule or episome. The EBV episome consists of long and short unique sequences (U.S. and UL) separated by a “large internal repeat sequence (IR1) and flanked by” terminal repeats (TR) at each end of the genome. UL sequence is subdivided into repetitive elements (IR2, IR3 and IR4).
The EBV genome contains over 100 ORFs (open reading frames) coding potential of many other polypeptides, have been characterized although only a tiny part of them. Immortalized lymphoblastoid cell lines express six EBV nuclear antigen: EBNA-1, 2, 3A, 3B, 3C and LP and three membrane proteins: LMP-1, LMP-2A and LMP-2B.
The nuclear antigen EBNA-1 is a protein of about 76 kDa. Their size varies among different EBV isolates and is therefore a good marker to identify the different strains. Shows a DNA-binding activity and is secured with high affinity to the place of episomal viral replication (oRipa). This binding leads to the initial replication of the EBV genome and is important in maintaining the episomal state.
The nuclear antigen EBNA-2 is a specific transactivator of viral and cellular genes. In Burkitt lymphoma EBV (-) transfection with EBNA-2. In cells immortalized B EBNA-2 modulates the expression of cell activation antigens (eg CD23, CD21) and lymphocyte function antigen (CD11a, CD18, CD58). Basically based on the differences of the EBNA-2 ORF are two types of EBV: EBV-1 (EBNA-2 of 491 amino acids) and EBV-2 (EBNA-2 of 443 amino acids) that show different capacities transformants, and the EBV- 1 is more efficient immortalizing lymphocytes (4).
The functions of EBNA-3 ORFs are little known, are markedly hydrophilic and their RNAs are transcribed at low number of copies. Recent data indicate that EBNA-3C are essential for B lymphocyte transformation This ORF is activated by EBNA-2 and modulates the transcription Through interaction with protein J kappa (5).
The only EBV protein with transforming activity sufficiently tested is LMP-1. In vitro is essential for B lymphocyte transformation in cell lines linfocitoides with the assistance of EBV. Induces many of the signs of activation of infected B cells as the expression of CD23, CD11a, CD18, CD58 and intracellular adhesion molecule 1 (ICAM-1). LMP-1 also shows transforming effects on fibroblast cell lines mammals produce more growth without substrate and inhibiting the effects of cell-cell contact. In transgenic mice the expression of LMP-1 in skin produces hypertrophy of the epidermis and in human epithelial cells increases the expression of epidermal growth factor receptor (6) and that the cytoplasmic tail of this protein interacts with the factor associated with tumor necrosis ( TRAF-3) communicating a signal of growth (7). LMP-1 protein is localized in the cell membrane associated with vimentin.