Transcriptional activation by the human herpesvirus-8-encoded interferon regulatory factor

Roan, Florence; Zimring, James C.; Goodbourn, Stephen; Offermann, Margaret K.

doi:10.1099/0022-1317-80-8-2205

Cited by 27 publications

(20 citation statements)

References 16 publications

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“…These mechanisms involve binding to some of the cellular IRFs and to coadaptors that link transcription factors to the RNA polymerase holoenzyme (Jayachandra et al, 1999;Burysek et al, 1999a;Seo et al, 2000;Li et al, 2000; Lin et al, 2001). The multifunctional properties of vIRF-1 are illustrated further by the observation that, although the protein is a transcription inhibitor, in some settings it can act as an activator (Roan et al, 1999). In addition, vIRF-1 is able to transform cells in culture which are then able to form tumours in nude mice (Gao et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Transcription mapping of human herpesvirus 8 genes encoding viral interferon regulatory factors

Cunningham

Barnard

Blackbourn

et al. 2003

Journal of General Virology

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The human herpesvirus 8 (HHV-8) genome contains four tandemly arranged genes encoding viral interferon regulatory factors (vIRF-1 to 4) located between genes 57 and 58. Transcript mapping techniques were employed to determine the sizes, ends and splicing patterns of mRNAs specified by these genes in HHV-8-infected cell lines untreated or chemically induced into the lytic growth cycle. Depending on the cell line used, vIRF-3 transcription was minimally or not induced (i.e. expressed with latent kinetics), whereas the other vIRFs were inducible (i.e. expressed with lytic kinetics). Each gene possessed its own promoter (or promoters) and polyadenylation sites, and all but vIRF-1 were spliced from two exons. vIRF-1 was transcribed in uninduced and induced cells from a single initiation site preceded by a TATA box, with the possible use of an additional TATA box and initiation site in uninduced cells. In induced cells, vIRF-2 was transcribed from a single major initiation site preceded by a TATA box, and vIRF-4 was expressed from two sites each preceded by a TATA box. Transcripts for these genes were insufficiently abundant in uninduced cells to map the 59-ends. vIRF-3 lacks an obvious TATA box and exhibited heterogeneous 59-ends in uninduced and induced cells. These data clarify and extend our understanding of the structure and transcription of the HHV-8 vIRF genes. INTRODUCTIONGenome sequences have been published for two strains of human herpesvirus 8 [HHV-8; also known as Kaposi's sarcoma-associated herpesvirus (KSHV)] by Russo et al. (1996) (accession no. U75698) and Neipel et al. (1997) (U93872). In addition to genes that are common to the members of the genus Rhadinovirus, several genes are unique to HHV-8 or found only in closely related species (for reviews, see Schulz, 1998;. A cluster of such genes is located in a 10 kbp region between open reading frames (ORFs) 57 and 58. Russo et al. (1996) described this region as containing an ORF (K9) whose encoded protein is related to cellular interferon regulatory factors (IRFs), plus two other protein-coding regions (K10 and K11), as illustrated in the upper part of Fig. 1. Other regions bearing amino acid similarity to IRFs were also noted, two upstream from K10 and one upstream from K11. Neipel et al. (1997) identified another ORF between K10 and K11, termed K10.1 (or K10.5), which corresponds closely to one of the IRF-like regions identified by Russo et al. (1996). Data from several groups subsequently indicated that this region of the genome contains four vIRF genes, one unspliced (vIRF-1 from K9) and three spliced (vIRF-2 from K11, vIRF-3 from K10.5 and vIRF4 from K10), as illustrated in the lower part of Fig. 1. The vIRF genes presumably arose by capture of cellular sequences followed by gene duplication events. The only other herpesvirus known to possess vIRFs is rhesus rhadinovirus (RRV), a close relative of HHV-8 (Searles et al., 1999;Alexander et al., 2000). RRV possesses eight tandem vIRFs, none of which appears to be spliced.Expression of HHV-8 genes is...

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Section: Introductionmentioning

confidence: 99%

Transcription mapping of human herpesvirus 8 genes encoding viral interferon regulatory factors

Cunningham

Barnard

Blackbourn

et al. 2003

Journal of General Virology

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“…Although vIRF-1 does not directly bind to DNA, it activates transcription when targeted to promoters by a heterologous DNA binding domain (432); in fact, direct transactivation of the c-myc promoter by vIRF-1 is required for transformation, and CBP coactivates c-myc with vIRF-1 (234). However, vIRF-1 has been best characterized for inhibiting the transcriptional programs induced by exogenous IFNs (174,293), specifically by blocking transcriptional activation by the cellular proteins IRF-1 and IRF-3.…”

Section: Lytic Genes and Kshv Pathogenesismentioning

confidence: 99%

Molecular Genetics of Kaposi's Sarcoma-Associated Herpesvirus (Human Herpesvirus 8) Epidemiology and Pathogenesis

Dourmishev

Palmeri

et al. 2003

Microbiol Mol Biol Rev

309

367

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Kaposi's sarcoma had been recognized as unique human cancer for a century before it manifested as an AIDS-defining illness with a suspected infectious etiology. The discovery of Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus-8, in 1994 by using representational difference analysis, a subtractive method previously employed for cloning differences in human genomic DNA, was a fitting harbinger for the powerful bioinformatic approaches since employed to understand its pathogenesis in KS. Indeed, the discovery of KSHV was rapidly followed by publication of its complete sequence, which revealed that the virus had coopted a wide armamentarium of human genes; in the short time since then, the functions of many of these viral gene variants in cell growth control, signaling apoptosis, angiogenesis, and immunomodulation have been characterized. This critical literature review explores the pathogenic potential of these genes within the framework of current knowledge of the basic herpesvirology of KSHV, including the relationships between viral genotypic variation and the four clinicoepidemiologic forms of Kaposi's sarcoma, current viral detection methods and their utility, primary infection by KSHV, tissue culture and animal models of latent- and lytic-cycle gene expression and pathogenesis, and viral reactivation from latency. Recent advances in models of de novo endothelial infection, microarray analyses of the host response to infection, receptor identification, and cloning of full-length, infectious KSHV genomic DNA promise to reveal key molecular mechanisms of the candidate pathogeneic genes when expressed in the context of viral infection

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“…Since vIRF1 is a strong transactivator (38,40), the C-terminal deletion construct, vIRF1⌬C (aa 1 to 360) fused to the DBD of GAL4, was used as bait ( Fig. 1A).…”

Section: Identification Of Cellular Proteins Interacting With Virf1mentioning

confidence: 99%

“…The vIRF1 protein associates with p300/CREB binding protein (CBP), leading to the inhibition of transactivation of CBP, histone acetyltransferase activity of p300 and the formation of transcriptionally active IRF3-p300/CBP complexes (4,23,25,40). Earlier studies have demonstrated that vIRF1 acts as a transcriptional activator, despite its many repressive activities (38).…”

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confidence: 99%

Viral Interferon Regulatory Factor 1 of Kaposi's Sarcoma-Associated Herpesvirus Interacts with a Cell Death Regulator, GRIM19, and Inhibits Interferon/Retinoic Acid-Induced Cell Death

Seo

Lee

Shim

et al. 2002

J Virol

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Transcriptional activation by the human herpesvirus-8-encoded interferon regulatory factor

Cited by 27 publications

References 16 publications

Transcription mapping of human herpesvirus 8 genes encoding viral interferon regulatory factors

Transcription mapping of human herpesvirus 8 genes encoding viral interferon regulatory factors

Molecular Genetics of Kaposi's Sarcoma-Associated Herpesvirus (Human Herpesvirus 8) Epidemiology and Pathogenesis

Viral Interferon Regulatory Factor 1 of Kaposi's Sarcoma-Associated Herpesvirus Interacts with a Cell Death Regulator, GRIM19, and Inhibits Interferon/Retinoic Acid-Induced Cell Death

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