Transcriptional activation by the pseudorabies virus immediate early protein.

Martin, Katherine J.; Lillie, James W.; Green, Michael R.

doi:10.1101/gad.4.12b.2376

Cited by 39 publications

(42 citation statements)

References 34 publications

(52 reference statements)

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Section: Viral Transcription Activators and The Transcription Cascadementioning

confidence: 99%

“…Like most typical cellular activators, IE180 contains a separate domain for DNA-binding and another for trans-activation (258,441). A strong acidic activation domain maps to the N terminus (amino acids 1 to 34) of IE180 (258). In vivo, IE180 has been shown to activate gene expression from the following PRV promoters: US4 (gG), UL12 (AN), UL22 (gH), UL23 (thymidine kinase), and UL41 (vhs) (73,312,389).…”

Section: Viral Transcription Activators and The Transcription Cascadementioning

confidence: 99%

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

Pomeranz

Reynolds

Hengartner

2005

Microbiol Mol Biol Rev

707

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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Section: Viral Transcription Activators and The Transcription Cascadementioning

confidence: 99%

Section: Viral Transcription Activators and The Transcription Cascadementioning

confidence: 99%

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

Pomeranz

Reynolds

Hengartner

2005

Microbiol Mol Biol Rev

707

657

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“…Protein-protein interactions between transcription factors need not always require protein-DNA interactions between both proteins in the complex (22,26). Elucidation of the mechanisms by which transcription factors interact is important for understanding transcriptional control and ultimately differentiation.…”

mentioning

confidence: 99%

PU.1 recruits a second nuclear factor to a site important for immunoglobulin kappa 3' enhancer activity.

et al. 1992

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PU.1 is a B-cell- and macrophage-specific transcription factor. By an electrophoretic mobility shift assay and dimethyl sulfate methylation interference assays, we show that PU.1 binds to DNA sequences within the immunoglobulin kappa 3' enhancer (kappa E3'). Binding of PU.1 to the kappa E3' enhancer assists the binding of a second tissue-restricted factor, NF-EM5, to an adjacent site. Binding of NF-EM5 to kappa E3' DNA sequences requires protein-protein interaction with PU.1 as well as specific protein-DNA interactions. This is the first known instance of PU.1 interacting with another cellular protein. NF-EM5 does not cofractionate with PU.1, suggesting that it is a distinct protein and is not a posttranslational modification of PU.1. UV-crosslinking studies and elution from sodium dodecyl sulfate-polyacrylamide gels indicate that NF-EM5 is a protein of approximately 46 kDa. Site-directed mutagenesis studies of the PU.1- and EM5-binding sites indicate that these sites play important roles in kappa E3' enhancer activity. By using a series of PU.1 deletion constructs, we have identified a region in PU.1 that is necessary for interaction with NF-EM5. This segment encompasses a 43-amino-acid region with PEST sequence homology, i.e., one that is rich in proline (P), glutamic acid (E), serine (S), and threonine (T).

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“…The orthologs are highly homologous in regions 2 and 4 but exhibit little or no homology in region 1, 3, or 5, except for a conserved serine-and acidic residue-rich motif located in either region 1 or 5. Mutational analyses of one or more of these orthologs have revealed the following: (i) residues in region 1 (ICP4 aa 1 to 315) function as a transactivation domain (32,40,49,55), bind to the cellular EAP protein (EBER-associated protein) (31), contribute to the regulation of ICP4 functions by ICP27 (43), and are required for formation of a complex with DNA that contains TBP and TFIIB (47); (ii) residues in region 2 …”

mentioning

confidence: 99%

Identification of a Motif in the C Terminus of Herpes Simplex Virus Regulatory Protein ICP4 That Contributes to Activation of Transcription

Bruce

Wilcox

2002

J Virol

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Expression of most viral genes during productive infection by herpes simplex virus is regulated by the viral protein ICP4 (also called IE175 or Vmw175). The N-terminal portion of ICP4 contains well-defined transactivation, DNA binding, and dimerization domains that contribute to promoter regulation. The C-terminal half of ICP4 contributes to the activity of ICP4, but the functional motifs have not been well mapped. To localize functional motifs in the C-terminal half of ICP4, we have compared the relative specific activities of ICP4 variants in transient-transfection assays. Deletion of the C-terminal 56 residues reduces the specific activity more than 10-fold. Mutational analysis identified three consecutive residues (1252 to 1254) that are conserved in ICP4 orthologs and are essential for full activity, especially in the context of ICP4 variants with a deletion in the N-terminal transactivation domain. Recombinant viruses that encode variants of ICP4 with mutations in the N-terminal transactivation domain and/or the extreme C terminus were constructed. The phenotypes of these recombinant viruses support the hypothesis that efficient promoter activation by ICP4 requires motifs at both the N and C termini. The data suggest that the C terminus of ICP4 functions not as an independent transactivation domain but as an enhancer of the ICP4 N-terminal transactivation domain. The data provide further support for the hypothesis that some ICP4 motifs required for promoter activation are not required for promoter repression and suggest that ICP4 utilizes different cellular factors for activation or repression of viral promoters.During productive infection by herpes simplex virus type 1 (HSV-1), approximately 75 genes encoded within the linear 152-kbp viral genome are transcribed by RNA polymerase II in three sequential phases designated immediate early (IE or ␣), early (E or ␤), and late (L or ␥) (for a review, see reference 52). The immediate-early protein ICP4 (infected-cell polypeptide 4) is required for efficient transcription of early and late viral genes and thus is essential for productive infection. The immediate-early proteins ICP0, ICP22, and ICP27 enhance expression of early and late genes at both transcriptional and posttranscriptional levels and contribute to some functions of ICP4 (52).ICP4 is a 1,298-amino-acid (aa) phosphoprotein that binds DNA in a sequence-specific manner as a homodimer (14,16,17,34). ICP4 represses transcription from three viral genes (LAT, ICP4, and ORF-P) that have a high-affinity ICP4 binding site spanning the transcription initiation site (1,16,20,21,28,30,41,42). ICP4 stimulates transcription from early and late viral promoters through interactions with viral DNA and cellular proteins that are poorly understood. Although the ICP4 DNA binding domain is essential for activation of transcription (39, 45), extensive analyses have not revealed a specific sequence that binds ICP4 with high affinity and is common to all promoters activated by ICP4 (13, 52). The observation that the minima...

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Transcriptional activation by the pseudorabies virus immediate early protein.

Cited by 39 publications

References 34 publications

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

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

PU.1 recruits a second nuclear factor to a site important for immunoglobulin kappa 3' enhancer activity.

Identification of a Motif in the C Terminus of Herpes Simplex Virus Regulatory Protein ICP4 That Contributes to Activation of Transcription

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