Transcriptional control of herpesvirus gene expression: gene functions required for positive and negative regulation.

Abstract

We have used an in vitro nuclear run-off assay to measure the levels of transcription of specific herpes simplex virus genes at different times during a lytic infection. We analyzed the effects of inhibition of DNA replication and of defects in two herpes simplex virus regulatory proteins on the transcription of these genes. We present evidence that the transcription of the aJCP4 gene is negatively regulated during a lytic infection. The regulation of ICP4 gene transcription requires the fi protein ICP8 (where ICP = infected cell polypeptide). Transcription of the PICP8, yICP5, and y2 glycoprotein C (gC) genes was dependent on ICP4, and transcription of the y2gC gene was strongly inhibited when DNA replication was blocked. Defects in ICP8 also resulted in increased levels of transcription of the ICP4, ICP8, ICP5, and gC genes from parental viral genomes. Our results suggest that ICP8 may be important in maintaining the highly ordered cascade of viral gene expression. 256The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

A specific 15-bp TATA box promoter element is required for expression of a herpes simplex virus type 1 late gene.

“…Nuclear runoff transcription assays have yielded conflicting results concerning the role of viral DNA replication in expression of ~2 genes. Godowski and Knipe (1986) have reported that transcriptional induction of the ~/2 gC gene was dependent on viral DNA replication. In contrast, Weinheimer and McKnight (1987)have reported that activation of late gene transcription precedes viral DNA replication, suggesting that post-transcriptional events play an important role in the production of stable late transcripts.…”

“…These genes are transcribed by the host cell RNA polymerase II, and expression is largely regulated at the level of transcription (Godowski and Knipe 1986;Weinheimer and McKnight 1987). The IE genes are transcribed first and are defined as those HSV genes that are expressed in the absence of prior de novo protein synthesis .…”

Update On Emerging Antivirals For The Management Of Herpes Simplex Virus Infections: A Patenting Perspective

“…U L 9 binds to ori and U L 29 stimulates helicase-primase and polymerase activities. Further U L 29 negatively regulates the transcription of β proteins post viral DNA replication [69][70][71][72]. HSV DNA replicates via a theta mechanism initially and continues via sigma or rolling-circle mechanism [73].…”

Prokaryotic expression and characteristics of duck enteritis virus UL29 gene

“…For herpes simplex virus, ICP8, a 130 kDa polypeptide, is expressed as a β or delayed-early-gene product and one of seven virus-encoded proteins required for replication of the herpes simplex virus genome (Littler et al, 1983;Powell et al, 1981;Challberg, 1986;Conley et al, 1981). According to the previous research, ICP8 has abilities to bind DNA in vitro and in vivo, down-regulate the expression of viral genes from parental genomes, localize in the cell nucleus, stimulate late-gene expression from progeny templates, and promote organization of nuclear structures involved in viral and cellular DNA replication (Bayliss et al, 1975;Knipe and Spang, 1982;Knipe, 1991, 1992;Godowski and Knipe, 1986).…”