The human herpesvirus-8 ORF 57 gene and its properties

Bello, Leonard J.; Davison, Andrew J.; Glenn, Mark A.; Whitehouse, Adrian; Rethmeier, Nikki; Schulz, Thomas F.; Clements, J. Barklie

doi:10.1099/0022-1317-80-12-3207

Cited by 72 publications

(85 citation statements)

References 43 publications

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“…versions of the sequences were cloned in a pCDNA6-v5-hisA vector (Invitrogen). The cDNA sequences encoding ORF57 of KSHV, HSV, and RRV (2,12,27) were cloned in pEF1-v5-hisA (Invitrogen). The prespliced form of the ORF57 sequence was amplified directly from the viral genome of the RRV 26-95 strain and cloned into pEF1-v5-hisA.…”

Section: Methodsmentioning

confidence: 99%

Rhesus Monkey Rhadinovirus ORF57 Induces gH and gL Glycoprotein Expression through Posttranscriptional Accumulation of Target mRNAs

Shin

Desrosiers

2011

J Virol

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Open reading frame 57 (ORF57) of gamma-2 herpesviruses is a key regulator of viral gene expression. It has been reported to enhance the expression of viral genes by transcriptional, posttranscriptional, or translational activation mechanisms. Previously we have shown that the expression of gH and gL of rhesus monkey rhadinovirus (RRV), a close relative of the human Kaposi's sarcoma-associated herpesvirus (KSHV), could be dramatically rescued by codon optimization as well as by ORF57 coexpression (J. P. Bilello, J. S. Morgan, and R. C. Desrosiers, J. Virol. 82:7231-7237, 2008). We show here that ORF57 coexpression and codon optimization had similar effects, except that the rescue of expression by codon optimization was temporally delayed relative to that of ORF57 coexpression. The transfection of gL mRNA directly into cells with or without ORF57 coexpression and with or without codon optimization recapitulated the effects of these modes of induction on transfected DNA. These findings suggested an important role for the enhancement of mRNA stability and/or the translation of mRNA for these very different modes of induced expression. This conclusion was confirmed by several different measures of gH and gL mRNA stability and accumulation with or without ORF57 coexpression and with or without codon optimization. Our results indicate that RRV gH and gL expression is severely limited by the stability of the mRNA and that ORF57 coexpression and codon optimization independently induce gH and gL expression principally by allowing accumulation and translation of these mRNAs.

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Section: Methodsmentioning

confidence: 99%

Rhesus Monkey Rhadinovirus ORF57 Induces gH and gL Glycoprotein Expression through Posttranscriptional Accumulation of Target mRNAs

Shin

Desrosiers

2011

J Virol

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“…Plasmids pGBKT7-ORF57 FL and pGBKT7-ORF57 small (containing the ORF57 gene 2nd exon, aa 181-455) were used for in vitro transcription/translation of the ORF57 protein. ORF57 FL and 2nd exon DNA sequences were excised as XhoI and PstI fragments from pKS4 and pKS1 (23), respectively, and cloned into SalI and PstI sites of pGBKT7 (Clontech), resulting in loss of both XhoI and SalI sites from pGBKT7-ORF57 FL and small. Plasmids pcDNA4-gORF57 (FL) and pcDNA4-cORF57 (FL) contain full-length genomic and cDNA sequences, respectively, driven by a human cytomegalovirus (HCMV) promoter encoding the ORF57 (aa 1-455) protein.…”

Section: Methodsmentioning

confidence: 99%

“…By contrast, although transcript mapping is not yet complete, the KSHV genome contains several spliced genes (reviewed in Refs. 4 and 27), including the ORF57 gene itself (23). Furthermore, because expression of ORF57 gave only a slight decrease in reporter gene activity from intron-containing reporter constructs (21,22), in virus-infected cells ORF57 may not profoundly inhibit pre-mRNA splicing.…”

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confidence: 99%

“…ICP27 has been shown to bind RNA targets that are widely distributed throughout the HSV-1 genome (20). Like ICP27, KSHV ORF57 protein predominantly localizes to the nucleus (21)(22)(23) and can shuttle between the nucleus and cytoplasm (23). A post-transcriptional mode of ORF57 action was suggested as its expression increased the accumulation of cytoplasmic mRNA (21,22).…”

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confidence: 99%

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The Evolutionarily Conserved Kaposi's Sarcoma-associated Herpesvirus ORF57 Protein Interacts with REF Protein and Acts as an RNA Export Factor

Malik¹,

Blackbourn

Clements

2004

Journal of Biological Chemistry

138

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shown to function as a CRM1-independent nuclear mRNA export factor, promoting export of mRNAs that are poor substrates for splicing. The ␥-herpesvirus ORF57 protein, and its ␣-1 herpesvirus ICP27 counterpart both export RNA through pathways involving REF and TAP proteins, although divergence of these herpesvirus subfamilies occurred some 180 -210 million years ago. The TAP-mediated cellular mRNA export pathway is CRM1-independent. However, human immunodeficiency virus type 1 Rev protein-mediated RNA export, which is CRM1-dependent, was considerably inhibited by ORF57, suggesting that Rev and ORF57 compete for a common export component. These data strengthen arguments that TAP and CRM1 pathways converge in accessing similar components of the nuclear pore complex. We propose that ORF57-mediated RNA export may use different export factors to accommodate the KSHV-infected host cell environments, for example, in B-cells or endothelial cells and during the different phases of lytic virus replication.

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“…Polyadenylation signals are shown as vertical lines near the 39-ends of mRNAs. Transcription data for gene 57 are from Bello et al (1999).…”

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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The human herpesvirus-8 ORF 57 gene and its properties

Cited by 72 publications

References 43 publications

Rhesus Monkey Rhadinovirus ORF57 Induces gH and gL Glycoprotein Expression through Posttranscriptional Accumulation of Target mRNAs

Rhesus Monkey Rhadinovirus ORF57 Induces gH and gL Glycoprotein Expression through Posttranscriptional Accumulation of Target mRNAs

The Evolutionarily Conserved Kaposi's Sarcoma-associated Herpesvirus ORF57 Protein Interacts with REF Protein and Acts as an RNA Export Factor

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

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