Genomic Organisation and Key Viral Latent Functions

EBV was the first herpesvirus to have its complete DNA sequenced, as presented simplistically in Figure 6, determined (Baer et al., 1984). In its overall structure, with unique sequences interspersed with repetitive elements, the viral genome appears to be a mini-version of its human host, with one notable exception, that is, every repetitive region (IR1-IR4 and TR) includes ORFs, occurs within a gene and also encodes a protein. There is no 'junk' DNA, the role often assigned to repetitive sequences in cellular

Group

Sequence arrangement

Members

HHV6; HHV7

TR llllllllllllllllllll

llllllllllllllllllllllllllllllllll

TR IR1

IIIIIIIIIIlM

U4 IR

U5 TR

TR 1IIIIIIIIIII

an b

an c an

HV saimiri; HV ateles; mouse HV strais 68 (murine HV-4); KSHV (HHV8)

EBV (HHV4); baboon HV chimpanzee HV

Varicella-zoster virus (HHV3); marmoset HV; bovine HV-1; -5; ovine HV-1

HSV-1 (HHV1); HSV-2 (HHV2); HCMV (HHV5); simiae HV; Marek's disease HV-1 (gallid HV-2); turkey HV-1

Figure 5 Architecture of herpesvirus genomes, showing unique (U) and repetitive (R) regions. Viruses have been grouped in categories (A-E) and their designations are given on the right. According to the nomenclature used by different groups, LTR = left terminal repeat; RTR = right terminal repeat; TR = terminal repeat; IR = internal repeat; UL = long terminal repeat; US = short teminal repeat. Symbols used in group E viruses represent sequence arrangements within repeats. (Adapted from IARC, 1997, p. 35.)

The EBV genome Coordinates (kbp)

0 10 20 30 40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 190

BamHI restriction map BamHI W repeats

EBERs

B95-8 del.

EBNA1

CSTsiRU

BARF0

TR Ps

Figure 6 Physical map of the EBV genome, and location of some key gene and repetitive (IR) elements (see Figure 5). Coordinates for a 'typical' genome are given and genes allocated to the BamHI restriction enzyme fragment in which they are located (see Figure 10). The CSTs encompass several restriction fragments. Its transcript is shown. MIR-B contains the minimum viral sequence required for immortalization of B lymphocytes and MIR-E the minimum for epithelial cells. (From Griffin and Xue, 1998, Annals of Medicine, 30, 249-259.)

DNA, in EBV. Whereas genomes of the smaller tumour viruses, depending upon the stage in the cell cycle in which they are expressed, are classically divided into 'early' and 'late' ORFs, herpesviruses are divided into 'immediate early' (before DNA replication is initiated), 'early' and 'late' genes. An alternative classification divides their genes into 'latent' and 'lytic' functions. The latter, probably simplistic, classification is useful for discussion purposes

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