Abstract
During their productive cycle, herpesviruses exhibit a strictly regulated temporal cascade of gene expression that can be divided into three general stages: immediate-early (IE), early (E), and late (L). This expression program is the result of a complex interplay between viral and cellular factors at both the transcriptional and post-transcriptional levels, as well as structural differences within the promoter architecture for each of the three gene classes. Since the cellular enzyme RNA polymerase II (RNAP-II) is responsible for the transcription of herpesvirus genes, most viral promoters contain DNA motifs that are common with those of cellular genes, although promoter complexity decreases from immediate-early to late genes. Immediate-early and early promoters contain numerous cellular and viral cis-regulating sequences upstream of a TATA box, whereas late promoters differ significantly in that they lack cis-acting sequences upstream of the transcription start site (TSS). Moreover, in the case of the β- and γ-herpesviruses, a TATT box motif is frequently found in the position where the consensus TATA box of eukaryotic promoters usually localizes. The mechanisms of transcriptional regulation of the late viral gene promoters appear to be different between α-herpesviruses and the two other herpesvirus subfamilies (β and γ). In this review, we will compare the mechanisms of late gene transcriptional regulation between HSV-1, for which the viral IE transcription factors – especially ICP4 – play an essential role, and the two other subfamilies of herpesviruses, with a particular emphasis on EBV, which has recently been found to code for its own specific TATT-binding protein.
Highlights
Herpesviridae form a large family of enveloped double-stranded DNA viruses with large and complex genomes ranging from 120 to 250 kbp in length
This review will focus on recent studies that have started to unravel some of the mechanisms involved in β- and γ-herpesviruses late gene transcription
Few late viral promoters have been studied in such detail, but in all cases examined the same type of simplistic promoter structure has been revealed: a sequence comprised between positions −30 and +30 relative to the transcription start site (TSS), including a TATA box motif, appears to be the only important sequence allowing typical late gene regulation of transcription (Johnson and Everett, 1986b; Shapira et al, 1987; Chang et al, 1998; Serio et al, 1998; Tang et al, 2004)
Summary
Herpesviridae form a large family of enveloped double-stranded DNA viruses with large and complex genomes ranging from 120 to 250 kbp in length. The productive cycle starts with the expression of the immediate-early ( refers to as IE or α) genes characterized by their ability to be transcribed in the absence of de novo protein synthesis. These genes encode for viral regulatory proteins involved in transcriptional control of the early ( refers to as E or β) genes. For viral DNA amplification, herpesviruses encode their own DNA replication machinery as well as a number of enzymes that contribute to the biosynthesis of deoxynucleoside triphosphates
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