Splicing Inhibition at the Level of Spliceosome Assembly in the Presence of Herpes Simplex Virus Protein ICP27

Lindberg, Anette; Kreivi, Jan-Peter

doi:10.1006/viro.2001.1301

Cited by 59 publications

(59 citation statements)

References 36 publications

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“…2), the probe corresponded to the entire 3.0-kb HSV-1 insert of pgC. Radioactive labeling of the probes with 32 P was done using a randomprimer labeling kit (Invitrogen).…”

Section: Methodsmentioning

confidence: 99%

“…Many of ICP27's effects appear to be mediated posttranscriptionally. In various experimental settings, it has been demonstrated to (i) enhance expression of genes which contain weak poly(A) signals by stimulating 3Ј-end processing (37,38,56); (ii) stabilize beta interferon mRNA expressed from a transfected gene (2,43); (iii) inhibit pre-mRNA splicing (22,32); and (iv) enhance mRNA transport out of the nucleus (5,6,31,55,63). As might be expected for a posttranscriptional regulatory protein, ICP27 binds directly to RNA (2,25,41,55).…”

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confidence: 99%

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Transactivation of a Viral Target Gene by Herpes Simplex Virus ICP27 Is Posttranscriptional and Does Not Require the Endogenous Promoter or Polyadenylation Site

Perkins

Gregonis

Borge

et al. 2003

J Virol

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ICP27 is an essential herpes simplex virus type 1 (HSV-1) immediate-early protein that stimulates viral mRNA expression from many viral delayed-early and late genes during infection. One HSV-1 late gene which is highly dependent on ICP27 during infection is that encoding the glycoprotein C (gC). Here we report that the gC gene is specifically transactivated by ICP27 in transfected Vero cells. Using various gC plasmid constructs, we show that ICP27's stimulatory effects are independent of the gC gene's endogenous promoter and polyadenylation site. This suggests that ICP27-responsive elements lie in the transcribed body of the gC gene. We also show that transactivation of the gC gene by ICP27 is independent of other viral proteins, as ICP27 alone can transactivate the gC gene when its transcription is mediated by the human cytomegalovirus immediate-early gene promoter. However, when gC gene expression is driven by its endogenous promoter, the stimulatory effect of ICP27 requires additional transactivators. To explore the level at which ICP27 transactivates the gC gene, we established stably transfected Vero cell lines that have integrated copies of the gC gene under control of the cytomegalovirus immediate-early gene promoter. These gC genes are not constitutively expressed but can be efficiently induced by HSV-1 infection. Using nuclear run-on transcription assays, we show that transcriptional induction of the stably transfected genes is ICP27 independent. In contrast, accumulation of gC mRNA is very highly dependent on ICP27. Together, these results demonstrate that ICP27 posttranscriptionally activates mRNA expression from a biologically relevant viral target gene.Herpesviruses encompass a large group of medically important, nuclear-replicating double-stranded DNA viruses. Herpes simplex virus type 1 (HSV-1) is the most extensively studied of the herpesviruses and serves as a prototype for characterizing their fundamental replication mechanisms. In particular, much is understood about how HSV-1 regulates the expression of its genes during productive infection (reviewed in references 52 and 72). During such infections, HSV-1 efficiently commandeers the host RNA polymerase II machinery and other host components to express its own genes at high levels, while simultaneously suppressing host gene expression. Moreover, the virus is able to coordinate the expression of its approximately 80 genes in a temporally regulated cascade, consisting of the sequential expression of three viral gene sets: the immediate-early (IE), delayed-early (DE), and late (L) genes. The five IE genes are expressed immediately upon infection. Their transcription does not require any newly synthesized viral proteins but is enhanced by a virion protein,VP16, working in concert with cellular transcription factors. The IE genes encode four gene regulatory factors: ICP4, ICP0, ICP22, and ICP27. These proteins induce the expression of the DE genes, the majority of which encode proteins that are involved in viral DNA replication. Expression of L gen...

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“…2), the probe corresponded to the entire 3.0-kb HSV-1 insert of pgC. Radioactive labeling of the probes with 32 P was done using a randomprimer labeling kit (Invitrogen).…”

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Transactivation of a Viral Target Gene by Herpes Simplex Virus ICP27 Is Posttranscriptional and Does Not Require the Endogenous Promoter or Polyadenylation Site

Perkins

Gregonis

Borge

et al. 2003

J Virol

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“…PRV UL54 and UL41 are likely to encode potent regulators of both viral and cellular gene expression. In HSV-1, UL54 encodes ICP27, a multifunctional RNA-binding protein that stimulates or inhibits transcription in a gene-specific manner, inhibits pre-mRNA splicing, modulates pre-mRNA polyadenylation and stability, and exports viral mRNAs into the cytoplasm (83,166,167,223,244,267,271,336,358). While HSV-1 UL54 (ICP27) is expressed as an immediate-early gene, PRV UL54 is expressed with early kinetics (182).…”

Section: Ep0mentioning

confidence: 99%

Molecular Biology of Pseudorabies Virus: Impact on Neurovirology and Veterinary Medicine

Pomeranz

Reynolds

Hengartner

2005

Microbiol Mol Biol Rev

718

657

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Pseudorabies virus (PRV) is a herpesvirus of swine, a member of the Alphaherpesvirinae subfamily, and the etiological agent of Aujeszky's disease. This review describes the contributions of PRV research to herpesvirus biology, neurobiology, and viral pathogenesis by focusing on (i) the molecular biology of PRV, (ii) model systems to study PRV pathogenesis and neurovirulence, (iii) PRV transsynaptic tracing of neuronal circuits, and (iv) veterinary aspects of pseudorabies disease. The structure of the enveloped infectious particle, the content of the viral DNA genome, and a step-by-step overview of the viral replication cycle are presented. PRV infection is initiated by binding to cellular receptors to allow penetration into the cell. After reaching the nucleus, the viral genome directs a regulated gene expression cascade that culminates with viral DNA replication and production of new virion constituents. Finally, progeny virions self-assemble and exit the host cells. Animal models and neuronal culture systems developed for the study of PRV pathogenesis and neurovirulence are discussed. PRV serves as a self-perpetuating transsynaptic tracer of neuronal circuitry, and we detail the original studies of PRV circuitry mapping, the biology underlying this application, and the development of the next generation of tracer viruses. The basic veterinary aspects of pseudorabies management and disease in swine are discussed. PRV infection progresses from acute infection of the respiratory epithelium to latent infection in the peripheral nervous system. Sporadic reactivation from latency can transmit PRV to new hosts. The successful management of PRV disease has relied on vaccination, prevention, and testing

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“…Thus, repression of splicing is predicted to inhibit cellular gene expression without affecting the expression of most HSV genes. ICP27 inhibits splicing in vitro, upstream of the first catalytic step, implying a direct mode of action on spliceosome assembly or function (1,31,53). Indeed, recent studies demonstrate that ICP27 directly binds splicing factors, including SAP145 and several SR proteins (1,53).…”

Section: General Features Of Hsv-induced Host Shutoff: Context Of Vhsmentioning

confidence: 99%

Herpes Simplex Virus Virion Host Shutoff Protein: Immune Evasion Mediated by a Viral RNase?

Smiley

2004

J Virol

213

180

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Herpes simplex virus type 1 (HSV-1) is the prototypical member of the Herpesviridae, a large family of enveloped DNA viruses that infect diverse metazoans. It is also the defining example of the Alphaherpesvirinae, the neurotropic subfamily of herpesviruses. Like all herpesviruses, HSV displays both lytic and latent modes of interaction with its natural human host. Primary infection of epithelial cells produces the lytic response-virus replication followed by cell death. Progeny virus particles then infect adjacent sensory neurons, establishing a lifelong latent interaction. The latent viral genome is maintained in an extrachromosomal state in which only a restricted portion of the genome is transcribed. Latent genomes occasionally reactivate into the lytic cycle, producing a limited amount of progeny virus that gives rise to secondary infections of the epithelial sites enervated by the latently infected neurons.HSV executes a complex genetic program during lytic infection (reviewed in reference 47). Expression of most cellular genes is strongly suppressed, and three temporal classes of viral genes are sequentially activated in a regulatory cascade. Five viral immediate-early (IE) genes are expressed first, and four of these (ICP0, ICP4, ICP22, and ICP27) encode regulatory proteins that stimulate expression of the viral early (E) and late (L) genes. The E genes are activated next, giving rise to proteins required for replication of the viral genome. Viral DNA replication then ensues, augmenting IE-dependent expression of the L genes that encode the structural components of the virion.HSV differs from many other nuclear DNA viruses in that some of its key regulatory polypeptides are delivered into the host cell by the infecting virus particle. These virion regulators are located in the viral tegument-the space between the envelope and the nucleocapsid-and as such are injected into the newly infected cell immediately upon fusion of the viral envelope with the host cell plasma membrane. These proteins are therefore strategically poised to influence the very earliest events in the viral replication cycle. In the best-known case, the abundant tegument protein VP16 activates transcription of the viral IE genes, thereby contributing to the initial launch of the lytic program of gene expression (reviewed in reference 17). The tegument also contains vhs, the virion host shutoff protein encoded by HSV gene UL41. vhs is an mRNA-specific RNase that triggers rapid shutoff of host cell protein synthesis, disruption of preexisting polyribosomes, and degradation of host mRNAs in the absence of de novo viral gene expression (reviewed in reference 55). Here I summarize our present understanding of the mechanism of vhs action and discuss recent studies that point to intriguing roles in viral pathogenesis and immune evasion. Space limitations preclude an exhaustive review of the earlier literature; I therefore seek the indulgence of my colleagues and refer the interested reader to a recent review (55) and the introductory sections ...

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Splicing Inhibition at the Level of Spliceosome Assembly in the Presence of Herpes Simplex Virus Protein ICP27

Cited by 59 publications

References 36 publications

Transactivation of a Viral Target Gene by Herpes Simplex Virus ICP27 Is Posttranscriptional and Does Not Require the Endogenous Promoter or Polyadenylation Site

Transactivation of a Viral Target Gene by Herpes Simplex Virus ICP27 Is Posttranscriptional and Does Not Require the Endogenous Promoter or Polyadenylation Site

Molecular Biology of Pseudorabies Virus: Impact on Neurovirology and Veterinary Medicine

Herpes Simplex Virus Virion Host Shutoff Protein: Immune Evasion Mediated by a Viral RNase?

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